Behind the Genes

In this episode, we explore how individualised medicines are evolving from “n=1” treatments (a treatment effective for a single individual) into approaches that could transform care for many people living with rare conditions. Advances in genomic medicine are making it possible to design highly targeted treatments based on an individual’s genetic information. While these therapies may begin as bespoke solutions for a single patient, they can often be adapted, refined or reused to benefit others with similar conditions. While the research is evolving, the systems needed to deliver these treatments at scale are still catching up. From regulation to access, our guests discuss what needs to change to turn this potential into reality. Our host Sharon Jones, is joined by: Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England Mel Dixon, Participant Panel member and CEO and Founder of Cure DHDDS If you enjoyed today’s conversation, please like and share wherever you listen to your podcasts. “However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment.” You can download the transcript or read it below. Sharon: What if treatments once designed for just one person could now help many others? Thanks to advances in genomic medicine, regulations are changing and research is expanding. This opens up more options for treatments for rare conditions. But what does this mean and how close is real change? I'm Sharon Jones, and this is Behind the Genes. We look at how genomics is changing healthcare, covering everything from cutting-edge research to real-life stories. Individualised medicines are a fast-moving area, but there's still a big gap between scientific progress and what's actually happening to patients. You could call it the gap between hype and hope. Ana Lisa: However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment. Sharon: Coming up, we'll hear from Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England, and Consultant in Clinical Genetics at Cambridge University Hospital, as well as Mel Dixon, member of the Participant Panel at Genomics England and CEO and founder of Cure DHDDS. Mel opens this chat by explaining why developments in individualised healthcare really matter to her. Mel: This issue is really personal to me. I have three children, two of whom are affected with an ultra-rare DHDDS gene variant, for which there is currently no treatment. Their condition causes symptoms such as, well, it varies between mild to severe learning difficulties, seizures, tremors, and movement and coordination difficulties. But the, the most worrying thing for us was that this condition is actually also progressive. So over time it becomes more of a Parkinsonism and some patients experience dementia-like symptoms and psychosis. So for us to get a treatment that targets the genetic cause of, of their condition is, like, the most important thing in, in our lives. If we could intervene now, they could potentially, at the stage they're at, you know, live an independent life with, with some supports. But if the disease is left to progress, it would be a very different outcome for them. Sharon: I mean, that sounds so difficult and I can't even imagine how life is for you and your family. And I can see what is driving you to find anything to extend the life of your children and to give them that opportunity to, to have a better quality of life. And then Lisa. Ana Lisa: It's a huge burden for families to carry. And I think at the moment there's an additional layer of burden, which shouldn't fall on families, to feel like they need to forge a pathway for their child to have a chance of a treatment. That's, that's a lot to bear. Mel: I think as well, families feel they almost have to become mini scientists in their children's specific condition overnight, because you go to these appointments with the consultants and nobody's heard of the condition and they don't know, they just don't really know what to do with you. So they're asking you, you know, so tell me about this, this gene change. What, what does it do? What does it mean? So you have to become the mini professor in your child's condition to be able to advocate for them. We've had to really learn on our feet so that we're able to advocate and push for research into DHDDS, because without us doing it, nobody else was going to be. Sharon: Yeah. So that's, you know, that's partly what we're here and what this podcast is for, it's here to support families to, to understand this stuff. And Ana Lisa, can you just break it down to us, what is individualised medicines? Ana Lisa: An individualised medicine that's made for one individual person. In reality, sometimes there are other individuals that can also benefit from the same medicines, and sometimes actually, although the medicine is

In this explainer episode, we’ve asked Georgia Chan, Senior Data Wrangler at Genomics England, to explain what de-identified data is. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected]. You can download the transcript or read it below. Florence: What do we mean by de-identified data? My name is Florence Cornish, and today I'm here with Georgia Chan. Georgia is Senior Data Wrangler here at Genomics England, which just means that she cleans up and adds structure to complicated data so that it becomes usable, and she is going to be telling us much more about the topic of de-identified data. Georgia, I think it would be a good place to start by talking about the National Genomic Research Library, which is the library that we at Genomics England store data in. So maybe you could explain more about that and what kind of data is in there. Georgia: Sure. Thanks Florence. So, we have genomic data. Genomic data is information that comes from a person's DNA. It helps us understand how the body works and why disease happens. This can include whole genome sequencing data, variants found in genes, small differences that make each of us unique, and information about how genes function or how they differ between people. Genomic data does not include a person's name or who they are. It's biological information, not identity, and it's used to understand health and disease. It's really important to note that by nature, it's nature, genomic information is incredibly rich. We all have millions of common genetic variants, but your whole genome is unique to you. So although genomic data alone can't directly identify you, it still counts as personal data under data protection. We also have clinical data. Clinical data provides real world context for the genomic data. It shows what's happening in someone's health. This can include diagnosis of a disease or a symptom, treatments that have been received, health outcomes over time, such as remission or progression, and this clinical data that help researchers see how genetic differences relate to symptoms, treatment response, and long-term outcomes. So, we have both of these kinds of data. Genomic data on its own can be hard to interpret, and clinical data on its own only tells part of the story. Together, they allow researchers to better understand how diseases develop, helps them discover new or more targeted treatments, and it helps them improve diagnosis, care, and outcomes. And this is why both types of this data are used together in the National Genomic Research Library. Florence: And so, both of these data types, both clinical and genomic, we say that they are de-identified. But what exactly does that mean? Georgia: Yes, good question. De-identified data means that information which directly identifies a person has been changed or removed from a health record before researchers can access it. And in practice, it means that researchers cannot see who the person is. The data cannot be used to contact individuals, and a person's identity is protected by design, which means that necessary safeguards are embedded into every stage of a service or process. So, researchers work with the data, but not with people's identities. Florence: Could you tell me a little bit more about why it's so important to de-identify data in this way? Georgia: Sure. De-identification creates a safe middle ground. It means that data can be used to improve healthcare whilst people's privacy and trust is respected. So, without de-identification, every new research question would require individual contact and large-scale, long-term research would be extremely difficult. With de-identification, we reduce the risk of someone being identified. We prevent inappropriate use of data, and we ensure that data is used only for approved research. And it's important to note also that it sits alongside a list of other safeguards, so that helps ensure data is used responsibly, such as secure Research Environment, strict access control, independent ethical and governance approvals. And all of those safeguards are provided in Genomics England's Research Environment. Florence: I think a common question that people might have, or a question that I definitely had when I first heard the term, is how de-identified data is different from anonymous data. Georgia: Yes, it is a good question. So, anonymised data cannot be linked back to an individual and is no longer considered personal data, whereas de-identified anonymised data, it has identified as hidden from researchers, but it can still be relinked by a trusted authorised organisation if needed. So, in healthcare research, de-identification is often preferred because it allows long-term follow up. It also allows updates as new health information becomes available, and

Blood cancers are the fifth most common group of cancers in the UK. But for a small number of people, the condition may have an inherited genetic cause. In this episode of Behind the Genes, we explore the role of genetics in blood cancer, and what an inherited risk means for patients and their families. Our guests explain what blood cancer is, how inherited factors can increase risk, and why multidisciplinary teamwork is key to supporting families. They also look ahead to future advances, from whole genome sequencing to prevention trials. Our host Amanda Pichini, Clinical Director at Genomics England, is joined by: Dr Katie Snape, Principal Clinician at Genomics England and Consultant Cancer Geneticist Bev Speight, Principal Genetic Counsellor Dr Sarah Westbury, Consultant Haematologist “By doing whole genome sequencing we get all of the information about all of the changes that might have happened, we know whether any are inherited, but importantly, we’re certain of the ones that have just occurred in the cancer cells and can help guide us with their treatment.” You can download the transcript or read it below. Amanda: Hello, and welcome to Behind the Genes. Sarah: When we think about blood cancers, it’s a whole range of different conditions and when you talk to patients who are affected with blood cancers or are living with them, their experiences are often really different from one another, depending in part on what kind of blood cancer they have. We also know that blood cancers affect not just the cell numbers but also the way that those cells function, and so the range of symptoms that people can get is really variable. Amanda: I am your host, Amanda Pichini, clinical director at Genomics England and genetic counsellor. Today I’ll be joined by Dr Katie Snape, principal clinician at Genomics England and a consultant cancer geneticist in London, Bev Speight, a principal genetic counsellor in Cambridge, and Dr Sarah Westbury, and haematologist from Bristol. They’ll be talking about blood cancers and the inherited factors that increase blood cancer risk. If you enjoy this episode, we’d love your support, so please subscribe, rate and share on your favourite podcast app. Let’s get started. Thanks to everyone for joining us today on this podcast, we’re delighted to have so many experts in the room to talk to us about blood cancer. I’d love to start with each of you introducing yourself and telling us and the listeners a little bit about your role, so, Sarah, could we start with you? Sarah: Sure. It’s great to be here. My name’s Sarah Westbury, and I’m a consultant haematologist who works down in Bristol. And my interest in this area is I’m a diagnostic haematologist so I work in the laboratories here in the hospitals, helping to make a diagnosis of blood cancer for people who are affected with these conditions. And I also look after patients in clinic who have different forms of blood cancer, but particularly looking after families who have an inherited predisposition to developing blood cancer. And in the other half of my job, I work as a researcher at the University of Bristol. And in that part of my job, I’m interested in understanding the genetic basis of how blood counts are controlled and some of the factors that lead to loss of control of those normal blood counts and how the bone marrow functions and works. Amanda: Thank you. That’s really interesting, we’ll be looking forward to hearing more about your experience. Bev, we’ll come to you next. Bev: Thank you. Hello everyone, I’m Bev Speight, I’m a genetic counsellor, and I work at Addenbrooke’s Hospital in Cambridge. I work with families with hereditary cancers in the clinical genetic service, and for the last six years or so have been focused on hereditary blood cancers. So we’ve been helping our haematologists across the region to do genetic tests and interpret the results, and then in my clinic seeing some of the onward referrals that come to clinical genetics after a hereditary cause for blood cancer is found. I’m also part of the Council for the UK Cancer Genetics Group. Amanda: Thank you, Bev. And Katie, over to you. Katie: Hello, I’m Katie Snape. I’m a genetics doctor and I am a specialist in inherited cancer. So we look after anyone who might have an increased chance of developing cancer in their lifetime due to genetic factors. I am the chair of the UK Cancer Genetics Group, so that’s a national organisation to try and improve the quality of care and care pathways for people with inherited cancer risk in the UK. And I have a special interest in inherited blood cancers through my work at King’s College Hospital, I work in the haematology medicine service there seeing individuals who might have or have been diagnosed as having an inherited component to their blood cancers. So it’s great to be here. Amanda: Excellent, thank you for those introductions. I’d like to then dive right in and understand a little bit more about blood cancers. So, Sara

In this explainer episode, we’ve asked Réka Novotta, Research Ethics Operations Manager at Genomics England, to explain what informed consent is. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected]. You can download the transcript or read it below. Florence: What do we mean by informed consent? My name is Florence Cornish, and today I'm here with Réka, who is Research Ethics Operations Manager here at Genomics England, and she's going to be telling us much more about it. I think it would first be helpful Réka, if you could explain the word consent. Réka: The broad definition of consent is that it's the voluntary agreement given by an individual to participate in a particular activity. We all probably give consent to a lot of different things each day without really realizing it. So, you go on to read the news in the morning, and the website asks for your consent to process cookies. You maybe go to a routine GP appointment later, and you stick your arm out for them to measure your blood pressure. Maybe you even go to a podcast and you give consent to a host to record your voice. So, these are all based on affirmative action made by you while taking into consideration the information that's available to you. The technical definition of consent often includes that it's freely given, meaning that you are not coerced. That it’s specific, meaning when you stick your arm out for your doctor, you're only agreeing to that part of the examination, and perhaps most importantly, that person needs to be adequately informed for the consent to be meaningful. Florence: So you gave lots of really interesting examples there. I think it would be good to understand what we mean by informed consent and where this distinction comes in. How does it differ? Réka: By informed consent, we mean that the person consenting has been provided with all relevant and necessary information about the activity, in a format that is accessible and understandable for them. And that latter part of the sentence is really important, because if you go to the doctor and the doctor speaks to you in French, if you speak French, then wonderful, you have all the information that you need. But if you don't, even though the information is technically there, you not understanding it makes it impossible for your consent to be informed. Similarly, if you think about maybe an older person who's not familiar with technology, if they see a QR code, they might not necessarily know what to do with it, even if it would technically lead to all of the information that they would ever want to know about Genomics England. Florence: So you mentioned Genomics England, obviously we both work for Genomics England, this is a Genomics 101 podcast. So what do we mean by informed consent in the context of genomics? Where does it come into play? Réka: So if we think about informed in a traditional research study, they test a drug, the treatment either works or it doesn't work, and there's analysis of that data, and that's sort of the end of the process. With genomics, there's a huge amount of information that gets generated and analysed, and the field itself is rapidly evolving. So we may not have an answer today, but we might do tomorrow, which puts our participants' data in the research resource that we manage in a really unique position. Because of that, it's even more important perhaps for this consent to be ongoing. Consent is often incorrectly considered a tick box exercise, where you receive information, you consider the information, you make a decision, and that's sort of it. Whereas for genomics, it's important that it is an ongoing conversation and it doesn't just stop at the signing of a form. We also employ what's called a broad consent model. Genomics England manages the National Genomic Research Library, which rather than being a single study, is a resource for a wide range of research uses. It allows us to gain permission via the informed consent conversations for the storage and the use of data and samples for upcoming studies that we don't yet know about. And this eliminates the need to reconsent each participant every time a researcher starts to use their data for a new research project, and in turn, and this also feeds back to the need for ongoing conversation, a fully informed consent is very hard to achieve at the time of consenting. Florence: So you mentioned the National Genomic Research Library, and we actually did a previous explainer podcast episode about this. So, if listeners would like to learn more about it, you can check out our previous Genomics 101 episode: What is the National Genomic Research Library? Réka, I'd be interested to know, are there any challenges related to informed consent that are specific to the field of genomics? Réka: Ye

In this special episode, recorded live at the 2025 Genomics England Research Summit, host Adam Clatworthy is joined by parents, clinicians and researchers to explore the long, uncertain and often emotional journey to a genetic diagnosis. Together, they go behind the science to share what it means to live with uncertainty, how results like variants of uncertain significance (VUS) are experienced by families, and why communication and support matter just as much as genomic testing and research. The panel discuss the challenges families face when a diagnosis remains out of reach, the role of research in refining and revisiting results over time, and how collaboration between researchers, clinicians and participants could help shorten diagnostic journeys in the future. Joining Adam Clatworthy, Vice-Chair for the Participant Panel, on this episode are: Emma Baple – Clinical geneticist and Medical Director, South West Genomic Laboratory Hub Jamie Ellingford – Lead genomic data scientist, Genomics England Jo Wright – Member of the Participant Panel and Parent Representative for SWAN UK Lisa Beaton - Member of the Participant Panel and Parent Representative for SWAN UK Linked below are the episodes mentioned in the episode: What is the diagnostic odyssey? What is a Variant of Uncertain Significance? Visit the Genomics England Research Summit website, to get your ticket to this years event. You can download the transcript, or read it below. Sharon: Hello, and welcome to Behind the Genes. My name is Sharon Jones and today we’re bringing you a special episode recorded live from our Research Summit held in June this year. The episode features a panel conversation hosted by Adam Clatworthy, Vice-Chair of the Participant Panel. Our guests explore navigating the diagnostic odyssey, the often-complex journey to reaching a genetic diagnosis. If you’d like to know more about what the diagnostic odyssey is, check our bitesize explainer episode, ‘What is the Diagnostic Odyssey?’ linked in the episode description. In today’s episode you may hear our guests refer to ‘VUS’ which stands for a variant of uncertain significance. This is when a genetic variant is identified, but its precise impact is not yet known. You can learn more about these in another one of our explainer episodes, “What is a Variant of Uncertain Significance?” And now over to Adam. -- Adam: Welcome, everyone, thanks for joining this session. I’m always really humbled by the lived experiences and the journeys behind the stories that we talk about at these conferences, so I’m really delighted to be hosting this panel session. It’s taking us behind the science, it’s really focusing on the people behind the data and the lived experiences of all the individuals and the families who are really navigating this system, trying to find answers and really aiming to get a diagnosis – that has to be the end goal. We know it’s not the silver bullet, but it has to be the goal so that everyone can get that diagnosis and get that clarity and what this means for their medical care moving forwards. So, today we’re really going to aim to demystify what this diagnostic odyssey is, challenging the way researchers and clinicians often discuss long diagnostic journeys, and we’ll really talk about the vital importance of research in improving diagnoses, discussing the challenges that limit the impact of emerging research for families on this odyssey and the opportunities for progress. So, we’ve got an amazing panel here. Rather than me trying to introduce you, I think it’s great if you could just introduce yourselves, and Lisa, I’ll start with you. Lisa: Hi, I’m Lisa Beaton and I am the parent of a child with an unknown, thought to be neuromuscular, disease. I joined the patient Participant Panel 2 years ago now and I’m also a Parent Representative for SWAN UK, which stands of Syndromes Without A Name. I have 4 children who have all come with unique and wonderful bits and pieces, but it’s our daughter who’s the most complicated. Adam: Thank you. Over to you, Jo. Jo: Hi, I’m Jo Wright, I am the parent of a child with an undiagnosed genetic condition. So I’ve got an 11-year-old daughter. 100,000 Genomes gave us a VUS, which we’re still trying to find the research for and sort of what I’ll talk about in a bit. And I’ve also got a younger daughter. I joined the Participant Panel just back in December. I’m also a Parent Rep for SWAN UK, so Lisa and I have known each other for quite a while through that. Adam: Thank you, Jo. And, Jamie, you’re going to be covering both the research and the clinician side and you kind of wear 2 hats, so, yeah, over to you. Jamie: Hi, everyone, so I’m Jamie Ellingford and, as Adam alluded to, I’m fortunate and I get to wear 2 hats. So, one of those hats is that I’m Lead Genomic Data Scientist for Rare Disease at Genomics England and so work as part of a really talented team of scientists and engineers to help develop our bioinformatic pipelines, so computation

In this special end-of-year episode of Behind the Genes, host Sharon Jones is joined by Dr Rich Scott, Chief Executive Officer of Genomics England, to reflect on the past year at Genomics England, and to look ahead to what the future holds. Together, they revisit standout conversations from across the year, exploring how genomics is increasingly embedded in national health strategy, from the NHS 10-Year Health Plan to the government’s ambitions for the UK life sciences sector. Rich reflects on the real-world impact of research, including thousands of diagnoses returned to the NHS, progress in cancer and rare condition research, and the growing momentum of the Generation Study, which is exploring whether whole genome sequencing could be offered routinely at birth. This episode offers a thoughtful reflection on how partnership, innovation, and public trust are shaping the future of genomic healthcare in the UK and why the years ahead promise to be even more exciting. Below are the links to the podcasts mentioned in this episode, in order of appearance: How are families and hospitals bringing the Generation Study to life? How can cross-sector collaborations drive responsible use of AI for genomic innovation? How can we enable ethical and inclusive research to thrive? How can parental insights transform care for rare genetic conditions? How can we unlock the potential of large-scale health datasets? Can patient collaboration shape the future of therapies for rare conditions? https://www.genomicsengland.co.uk/podcasts/what-can-we-learn-from-the-generation-study “There is this view set out there where as many as half of all health interactions by 2035 could be informed by genomics or other similar advanced analytics, and we think that is a really ambitious challenge, but also a really exciting one.” You can download the transcript, or read it below. Sharon: Hello, and welcome to Behind the Genes. Rich: This is about improving health outcomes, but it’s also part of a broader benefit to the country because the UK is recognised already as a great place from a genomics perspective. We think playing our role in that won’t just bring the health benefits, it also will secure the country’s position as the best place in the world to discover, prove, and where proven roll out benefit from genomic innovations and we think it’s so exciting to be part of that team effort. Sharon: I’m Sharon Jones, and today I’ll be joined by Rich Scott, Chief Executive Officer at Genomics England for this end of year special. We’ll be reflecting on some of the conversations from this year’s episodes, and Rich will be sharing his insights and thoughts for the year ahead. If you enjoyed this episode, we’d love your support, so please subscribe, rate, and share on your favourite podcast app. So, let’s get started. Thanks for joining me today, Rich. How are you? Rich: Great, it’s really good to be here. Sharon: It’s been a really exciting year for Genomics England. Can you tell us a bit about what’s going on? Rich: Yeah, it’s been a really busy year, and we’ll dive into a few bits of the components we’ve been working on really hard. One really big theme for us is it’s been really fantastic to see genomics at the heart of the government’s thinking. As we’ll hear later, genomics is at the centre of the new NHS 10-year health plan, and the government’s life sciences sector plan is really ambitious in terms of thinking about how genomics could play a role in routine everyday support of healthcare for many people across the population in the future and it shows a real continued commitment to support the building of the right infrastructure, generating the right evidence to inform that, and to do that in dialogue with the public and patients, and it’s great to see us as a key part of that. It’s also been a really great year as we’ve been getting on with the various programmes that we’ve got, so our continued support of the NHS and our work with researchers accessing the National Genomic Research Library. It’s so wonderful to see the continued stream of diagnoses and actionable findings going back to the NHS. It’s been a really exciting year in terms of research, publications. In cancer, some really exciting publications on, for example, breast cancer and clinical trials. Really good partnership work with some industry partners, really supporting their work. For me, one of the figures we are always really pleased to see go up with time is the number of diagnoses that we can return thanks to research that’s ongoing in the research library, so now we’ve just passed 5,000 diagnostic discoveries having gone back to the NHS, it really helps explain for me how working both with clinical care and with research and linking them really comes to life and why it’s so vital. And then, with our programmes, it’s been great to see the Generation Study making good progress. So, working with people across the country, more than 25,000 families now recruited to the study

In this explainer episode, we’ve asked Dr Katie Snape, principal clinician at Genomics England, cancer geneticist, and specialist in inherited cancer, to explain how genomics can help us understand cancer. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected]. You can download the transcript or read it below. Flo: How can genomics help us understand cancer? I'm Florence Cornish, and today I'm joined with Katie Snape, who is Principal Clinician here at Genomics England, lead Consultant for Cancer Genetics at the Southwest Thames Centre for Genomics, and Chair of UK Cancer Genetics Group. So Katie, it's probably safe to say that everyone listening will have heard the word cancer before. Lots of people may have even been directly affected by it or know someone who has it or who has had it, and I think the term can feel quite scary sometimes and intimidating to understand. So, it might be good if you could explain what we actually mean when we say the word cancer. Katie: Thanks, Florence. So, our bodies are made up of millions of building blocks called cells. Each of these cells contains an instruction manual, and our bodies read this to build a human and keep our bodies working and growing over our lifetimes. So, this human instruction manual is our genetic information, and it's called the human genome. Throughout our lifetime, our cells will continue to divide and grow to make more cells when we need them. And this means that our genetic information has to contain the right instructions, which tell the cells to divide when we need new cells, like making new skin cells, for example as our old skin cells die, but they also need to stop dividing when we have enough new cells and we don't need anymore. And this process of growing but stopping when we don't need anymore cells, keeps our bodies healthy and functioning as they should do. However, if the instructions for making new cells goes wrong and we don't stop making new cells when we're supposed to, then these cells can grow out of control, and they can start spreading and damaging other parts of our body. And this is basically what cancer is. It's an uncontrolled growth of cells which don't stop when they're supposed to, and they grow and spread and damage other tissues in our body. Florence: So, you mentioned there that cancer can arise when the instructions in our cells go wrong. Could you talk a little bit more about this? How does it lead to cancer? Katie: Yeah. So the instructions that control how our cells should grow and then stop growing are usually called cancer genes. So our body reads these instructions a bit like we might read an instruction manual to perform a task. So if we imagine that one of these important cancer genes that has a spelling mistake, which means the body can't read it properly, then those cells won't follow the right instructions to grow and then stop growing like they should. So if our cells lose the ability to read these important instructions due to this type of spelling mistake, then that's when a cancer can develop. As these spelling mistakes happen in cancer genes, we call them genetic alterations or genetic variants. Florence: And so, when you're in the clinic seeing somebody who has cancer, what kinds of genomic tests can they have to help us find out a little bit more about it? Katie: So the genetic alterations that can cause cancer can happen in different cells. So that's why cancer can affect many different parts of the body. If a genetic alteration happens in a breast cell, then a breast cancer might develop. If the alteration happens in a skin cell, then a skin cancer could develop. We can take a sample from the cancer. This is often known as a biopsy, and then we can use this sample to extract the genetic information to read the instructions in the cancer cells, and when we do this, we are looking for spelling mistakes in the important cancer genes, which might of course, those cells to grow out of control. We can also look for patterns of alterations in the cells, which might tell us the processes that led to those genetic alterations occurring. For example, we can look at patterns of damage in the genetic information caused by cigarette smoke, or sunlight, or problems because the cell has lost its ability to mend and repair its genetic information. And we can also count the number of different alterations in the cancer cell, which might tell us how different that cancer cell is from our normal cells, and that can be important because we might be able to use medications to get our immune system to attack the cancer cells. So where we see genetic alterations in a cancer cell, we call them acquired or somatic alterations because we weren't born with them, but they've happened in a cell in our body at a later st

In this explainer episode, we’ve asked Amanda Pichini, clinical director at Genomics England and genetic counsellor, to explain what a genetic counsellor is. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected]. You can download the transcript or read it below. Florence: What is a genetic counsellor? I'm Florence Cornish, and today I'm joined with Amanda Pichini, a registered genetic counsellor and clinical director for Genomics England, to find out more. So, before we dive in, lots of our listeners have probably already heard the term genetic counsellor before, or some people might have even come across them in their healthcare journeys. But for those who aren't familiar, could you explain what we mean by a genetic counsellor? Amanda: Genetic counsellors are healthcare professionals who have training in clinical genomic medicine and counselling skills. So they help people understand complex information, make informed decisions, and adapt to the impact of genomics on their health and their family. They're expert communicators, patient advocates, and navigators of the ethical issues that genomics and genomic testing could bring. Florence: Could you maybe give me an example of when somebody might see a genetic counsellor? Amanda: Yes, and what's fascinating about genetic counselling is that it's relevant to a huge range of conditions, scenarios, or points in a person's life. Someone's journey might start by going to their GP with a question about their health. Let's say they're concerned about having a strong family history of cancer or heart disease, or perhaps a genetic cause is already known because it's been found in a family member and they want to know if they've inherited that genetic change as well. Or someone might already be being seen in a specialist service, perhaps their child has been diagnosed with a rare condition. A genetic counsellor can help that family explore the wide-ranging impacts of a diagnosis on theirs and their child's life, how it affects their wider family, what it might mean for future children. You might also see a genetic counsellor in private health centres or fertility clinics, or if you're involved in a research study too. Florence: And so, could you explain a bit more about the types of things a genetic counsellor does? What does your day-to-day look like, for example? Amanda: Most genetic counsellors in the UK work in the NHS as part of a team alongside doctors, lab scientists, nurses, midwives, or other healthcare professionals. Their daily tasks include things like analysing a family history, assessing the chance of a person inheriting or passing on a condition, facilitating genetic tests, communicating results, supporting family communication, and managing the psychological, the emotional, the social, and the ethical impacts of genetic risk or results. My day-to-day is different though. I and many other genetic counsellors have taken their skills to other roles that aren't necessarily in a clinic or seeing individual patients. It might involve educating other healthcare professionals or trainees, running their own research, developing policies, working in a lab, or a health tech company, or in the charity sector. For me, as Clinical Director at Genomics England, I bring my clinical expertise and experience working in the NHS to the services and programmes that we run, and that helps to make sure that we design, implement, and evaluate what we do safely, and with the needs of patients, the public, and healthcare professionals at the heart of what we do. My day-to-day involves working with colleagues in tech, design, operations, ethics, communications, and engagement, as well as clinical and scientific experts, to develop and run services like the Generation Study, which is sequencing the genomes of 100,000 newborn babies to see if we can better diagnose and treat children with rare conditions. Florence: So, I would imagine that one of the biggest challenges of being a genetic counsellor is helping patients to kind of make sense of the complicated test results or information, but without overwhelming them. So how do you balance kind of giving people the scientific facts and all the information they need, but while still supporting them emotionally? Amanda: This is really at the core of what genetic counsellors can do best, I think. Getting a diagnosis of a rare condition, or finding out about a risk that has a genetic component, can come with a huge range of emotions, whether that's worry, fear, or hope and relief. It can bring a lot of questions, too. What will this mean for my future or my family's future? What do you know about this condition? What sort of symptoms could I have? What treatments or screening might be available to me? So genetic counsellors are ab

In this explainer episode, we’ve asked Dr Emily Perry, research engagement manager at Genomics England, to explain what the Genomics England Research Environment is. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. You can listen to the previous episodes mentioned in this podcast How has a groundbreaking genomic discovery impacted thousands worldwide? What is the National Genomic Research Library If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected]. You can download the transcript or read it below. Florence: What is the Genomics England Research Environment? My name is Florence Cornish and I'm here with Emily Perry, Research Engagement Manager at Genomics England, to find out more. So Emily, before we dive into the Research Environment, let's set some context. Could you explain what Genomics England is aiming to do as an organisation? Emily: So, Genomics England provides genome sequencing in a healthcare setting for the National Health Service in England. As we sequence genomes for healthcare, the benefit is that we can also put that genomic and clinical data out for research in a controlled manner, and then that can also feed back into healthcare as well. So, it's really, this kind of cyclical process that Genomics England is responsible for. Florence: And so, what do we mean when we say Research Environment? Emily: So, the Research Environment is how our researchers can get access to that clinical and genomic data that we get through healthcare. So, it's a controlled environment, it's completely locked down, so it's kind of like a computer inside a computer. And in there, the researchers can access all of the data that we have and also a lot of tools for working with it in order to do their research. We refer to the data as the National Genomics Research Library, or the NGRL. The NGRL data is provided inside the Research Environment Florence: So you mentioned the National Genomic Research Library. If any listeners want to learn more about this, you can check out our previous Genomics 101 podcast: What is the National Genomic Research Library? And so Emily, could you talk about what kind of data is stored in this library? Emily: So the library is made up of both genomic data and clinical data, which the researchers use alongside each other. The genomic data includes what we call alignments, which is where we match the reads from sequencing onto a reference sequence, and variants, which is where we identify where those alignments differ from the reference sequence, and this is what we are looking for in genomic research. The clinical data includes the data that was taken from our participants at recruitment, so details of the rare disease, the cancer, that they have, but also medical history data. So, we work with the NHS and we're able to get full medical history for our participants as well. This is all fully anonymised, so there's no names, there's no dates of birth, there's no NHS numbers. It's just these identifiers which are used only inside the Research Environment and have no link to the outside world. Florence: And so how is this clinical and genomic data secured? Emily: So, as I said there's no names, there's no NHS numbers, there's no dates of birth. And we have very strict criteria for how people can use the data. So researchers, in order to get access to the Research Environment, they have to be a member of a registered institution, they have to submit a project proposal for what it is that they want to study with the data. There's also restrictions on how they can get the data out, so they do all their research inside, there's no way that they can do things like copy and paste stuff out or move files. The only way that they can get data out of the Research Environment is going through a process called Airlock, which is where they submit the files that they want to export to our committee, who then analyse it, check that it's in accordance with our rules and it protects our participants' safety and that only then would they allow them to export it. Florence: Who has access to the Research Environment? Emily: We have researchers working with the Research Environment all over the world. There's 2 kind of major groups. One of them is academia, so this will be researchers working in universities and academic institutions. The other side of it would is industry - so this will be biotech, startups, pharma companies, things like that. Florence: And finally, can you tell us about some of the discoveries that have been made using this data? Emily: There's lots of really cool things that have come out of the Research Environment. A recent story that came out of the Research Environment was the ReNU syndrome, it was initially just one family that they identified this in, and they were able to extend this discovery across and identify huge numbers

In this episode, we step inside the NHS to explore how the Generation Study is brought to life - from posters in waiting rooms to midwife training. We follow the journey of parents joining the study at the very start of their baby’s life, and hear from those making it happen on the ground. Our guests reflect on the teamwork between families and hospitals, the importance of informed consent, and the powerful insights this study could unlock for the future of care and research. Our host Jenna Cusworth-Bolger, Senior Service Designer at Genomics England, is joined by: Tracie Miles, Associate Director of Nursing and Midwifery at the South West Genomic Medicine Service Alliance, and Co-Investigator for the Generation Study at St Michael’s Hospital in Bristol Rachel Peck, parent participant in the Generation Study and mum to Amber If you enjoyed today’s conversation, please like and share wherever you listen to your podcasts. For more on the Generation Study, explore: Podcast: How has design research shaped the Generation Study Podcast: What can we learn from the Generation Study Podcast: What do parents want to know about the Generation Study Blog: Genomics 101 - What is the Generation Study Generation Study official website “I think from a parent’s point of view I guess that's the hardest thing to consent for, in terms of you having to make a decision on behalf of your unborn child. But I think why we thought that was worthwhile was that could potentially benefit Amber personally herself, or if not, there's a potential it could benefit other children.” You can download the transcript, or read it below. Jenna: Hi, and welcome to Behind the Genes. Rachel: I think if whole genome sequencing can help families get answers earlier, then from a parent perspective I think anything that reduces a long and potentially stressful journey to a diagnosis is really valuable. If a disease is picked up earlier and treatment can start sooner, then that could make a real difference to a child or even Amber’s health and development. Jenna: My name is Jenna Cusworth-Bolger and today I have the great pleasure to be your host. I’m a senior service designer at Genomics England specifically working with the hospitals involved in delivering the Generation Study. In March 2023 we started with our very first hospital, St. Michael’s in Bristol. I am today joined by Tracie Miles who I had the utter pleasure of working closely with when they were setting up. And we also have Rachel Peck, one of the mums who joined the study in Bristol. Regular listeners to this podcast may already be familiar with the Generation Study but for those who are not, the Generation Study is running in England and aims to sequence the genomes of 100,000 newborn babies from a cord blood sample taken at birth. The families consented to take part will have their babies screened for over 200 rare genetic conditions most of which are not normally tested for at birth. We expect only 1% of these babies to receive a condition suspected result, but for those 1,000 families that result could be utterly life changing as it could mean early treatment or support for that condition. Would you like to introduce yourselves and tell us what it means to you to have been that first hospital open in this landmark study. Tracie, I’ll come to you first. Tracie: Hi Jenna, lovely to be with you all this morning. And for those who are listening it is early in the morning, we get up early in the morning because we never know when these babies are going to be born on the Generation Study and we have to be ready for them. So, my name is Tracie, I am the Co-Investigator with the wonderful Andrew Mumford, and we work together with a huge team bringing this study to life in Bristol. I am also the Associate Director of Nursing and Midwifery at the South West Genomic Medicine Service Alliance. Jenna: Thanks Tracie. We’re also joined today by Rachel. Would you like to introduce yourself and your baby, and tell me when you found out about the Generation Study? Rachel: Hi, thank you for inviting me. My name’s Rachel, I’m based in Bristol. My baby is Amber; she was born four months ago in St. Michael’s hospital in Bristol. I first heard about the Generation Study when I was going to one of my antenatal appointments and saw some of the posters in the waiting room. Amber is napping at the moment, so hopefully she’ll stay asleep for long enough for the recording. Jenna: Well done, that's the perfect mum skill to get a baby to nap whilst you’re busy doing something online. So, Rachel, you said you heard about the study from a poster. When you first saw that poster, what were your initial thoughts? Rachel: I thought it was really interesting, I haven’t come across anything like that before and I thought the ability to screen my unborn baby at the time’s whole genome sounded really appealing. Jenna: Fantastic. So, what happened after the poster? Rachel: If I remember correctly, I scanned the QR code on the

In this explainer episode, we’ve asked Dr Nour Elkhateeb, clinical fellow at Genomics England and clinical geneticist for the NHS, to explain the role of a clinical geneticist. The previous episode mentioned in the conversation is linked below. What is the diagnostic odyssey? You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected]. You can download the transcript or read it below. Florence: What is a clinical geneticist? My name is Florence Cornish and I'm here with Nour Elkhateeb, clinical geneticist for the NHS and fellow at Genomics England, to find out more. So, Nour, before we dive into talking about clinical geneticists, could you explain what we mean by the term genetics? Nour: Hi Florence, so at its heart, genetics is the study of our genes and how they are passed down through families. Think of your genome as a huge, incredibly detailed instruction manual for building and running your body. This manual is written in a specific language, DNA, which is made up of millions of letters arranged in a specific order. And here is the interesting part, we all have tiny differences in our genetic spelling, which is what makes each of us unique. But sometimes a change in the instructions, a spelling mistake in a critical place, can affect health. Genetics is all about learning to read that manual, understand how changes in it can cause disease, how it's passed down through families and finding ways to help. Florence: And so, what kind of thing does a geneticist actually do? Nour: Well, the term geneticist can cover a few different roles, which often work together. Crudely speaking, you can think of two main types, laboratory geneticists and clinical geneticists. Laboratory geneticists are the incredible scientists who work behind the scenes. When we send a blood sample for genomic sequencing, they are the ones who use amazing technology to read the billions of letters in that person's instruction manual. The job is to find the one tiny spelling mistake among those billions of letters that might be causing a health problem. Clinical geneticists like me are medical doctors specialised in the field of genetics, and we work face-to-face with patients and families in a hospital or a clinic setting. You can think of us as the bridge between the incredibly complex science of the genomics lab and the real-life health journey of the person in front of them. We diagnose, manage and provide support for individuals and families who are affected by or at risk of genetic conditions. And we translate that complex genetic information into meaningful information for the patient, the family and the other doctors as well. Florence: So, let's talk a little bit more about clinical geneticists. What stage of someone's genomics journey are they likely to see you? What are some typical reasons they might get referred, for example? Nour: That's a really good question. So, people actually can be seen by clinical geneticists at almost any stage of life, and for many different reasons. Let me give you some examples. We see a lot of babies and children. A family may be referred to us if their baby is born with health problems that do not have a clear cause, or if a child is not developing as expected. And sometimes families may have been searching for answers for years, or what we call a diagnostic odyssey, but no one has been able to find a single unifying diagnosis to explain their challenges. And our job is to see if there is a genetic explanation that can connect all the dots. Florence: You touched there on the diagnostic odyssey, and I know we don't have time to dive into that right now, but if listeners want to learn more about this, then they can check out our previous Genomics 101 podcast: What is the Diagnostic Odyssey? So, Nour, we know that you see children and families in their genomics journeys. Do you see adults as well? Nour: Yes, indeed. We also see many adults who develop certain health conditions, such as cancer or certain types of heart disease, and their clinicians suspect they might be having an underlying inherited genetic cause, or it could be actually someone who is healthy themselves, but have a family history of a particular condition, and want to understand their own risk or the risk for their children and other family members. A classic example is in cancer genetics. A woman with breast cancer at a young age, or who has several family members who have also had it, she would be investigated to see if she carries a gene change that increases the risk of breast cancer and other cancers, and finding that actually would be critical for the treatment choices, and it has huge implications for her relatives. Also, a major part of our work is in the prenatal setting, so we might see a couple during a pregnancy if th

In this episode of Behind the Genes, we explore how Artificial Intelligence (AI) is being applied in genomics through cross-sector collaborations. Genomics England and InstaDeep are working together on AI and machine learning-related projects to accelerate cancer research and drive more personalised healthcare. Alongside these scientific advances, our guests also discuss the ethical, societal and policy challenges associated with the use of AI in genomics, including data privacy and genomic discrimination. Our guests ask what responsible deployment of AI in healthcare should look like and how the UK can lead by example. Our host, Francisco Azuaje, Director of Bioinformatics Genomics England is joined by Dr Rich Scott, Chief Executive Officer at Genomics England Karim Beguir - Chief Executive Officer at InstaDeep Harry Farmer – Senior Researcher at Ada Lovelace Institute If you enjoyed today’s conversation, please like and share wherever you listen to your podcasts. And for more on AI in genomics, tune in to our earlier episode: Can Artificial Intelligence Accelerate the Impact of Genomics? "In terms of what AI’s actually doing and what it’s bringing, it’s really just making possible things that we’ve been trying to do in genomics for some time, making these things easier and cheaper and in some cases viable. So really it’s best to see it as an accelerant for genomic science; it doesn’t present any brand-new ethical problems, instead what it’s doing is taking some fairly old ethical challenges and making these things far more urgent." You can download the transcript, or read it below. Francisco: Welcome to Behind the Genes. [Music plays] Rich: The key is to deliver what we see at the heart of our mission which is bringing the potential of genomic healthcare to everyone. We can only do that by working in partnership. We bring our expertise and those unique capabilities. It’s about finding it in different ways, in different collaborations, that multiplier effect, and it’s really exciting. And I think the phase we’re in at the moment in terms of the use of AI in genomics is we’re still really early in that learning curve. [Music plays] Francisco: My name is Francisco Azuaje, and I am Director of Bioinformatics at Genomics England. On today’s episode I am joined by Karim Beguir, CEO of InstaDeep, a pioneering AI company, Harry Farmer, Senior Researcher at the Ada Lovelace Institute, and Rich Scott, CEO of Genomics England. Today we will explore how Genomics England is collaborating with InstaDeep to harness the power of AI in genomic research. We will also dive into the critical role of ethical considerations in the development and application of AI technologies for healthcare. If you’ve enjoyed today’s episode, please like, share on wherever you listen to your podcasts. [Music plays] Let’s meet our guests. Karim: Hi Francisco, it’s a pleasure to be here. I am the Co-Founder and CEO of InstaDeep and the AI arm of BioNTech Group, and I’m also an AI Researcher. Harry: I’m Harry Farmer, I’m a Senior Researcher at the Ada Lovelace Institute, which is a think-tank that works on the ethical and the societal implications of AI, data and other emerging digital technologies, and it’s a pleasure to be here. Rich: Hi, it’s great to be here with such a great panel. I’m Rich Scott, I’m the CEO of Genomics England. Francisco: Thank you all for joining us. I am excited to explore this intersection of AI and genomics with all of you. To our listeners, if you wish to hear more about AI in genomics, listen to our previous podcast episode, ‘Can Artificial Intelligence Accelerate the Impact of Genomics’, which is linked in this podcast description. Let’s set the stage with what is happening right now, Rich, there have been lots of exciting advances in AI and biomedical research but in genomics it’s far more than just hype, can you walk us through some examples of how AI is actually impacting genomic healthcare research? Rich: Yeah, so, as you say, Francisco, it is a lot more than hype and it’s really exciting. I’d also say that we’re just at the beginning of a real wave of change that’s coming. So while AI is already happening today and driving our thinking, really we’re at the beginning of a process. So when you think about how genomics could impact healthcare and people’s health in general, what we’re thinking about is genomics potentially playing a routine part in up to half of all healthcare encounters, we think, based on the sorts of differences it could make in different parts of our lives and our health journey. There are so many different areas where AI, we expect, will help us on that journey. So thinking about, for example, how we speed up the interpretation of genetic information through to its use and the simple presentation of how to use that in life, in routine healthcare, through to discovery of new biomarkers or classification that might help us identify the best treatment for people. Where it’s making a difference

In this episode of Behind the Genes, we explore the hopes, concerns and complex questions raised by the idea of a lifetime genome — a single genomic record used across a person’s life to guide healthcare decisions. Drawing on conversations from Genomics England’s Public Standing Group on the lifetime genome, our guests explore what it might mean for individuals, families and society to have their genome stored from birth, and how it could transform healthcare. The discussion reflects on the potential for earlier diagnoses, better treatments and long-term prevention, alongside pressing ethical concerns such as data security, consent, and the impact on family dynamics. Participants share their views and discuss the future role of genomic data in medicine, with insights into how trust, equity and public dialogue must shape this evolving field. Our host for this episode, Dr Harriet Etheredge, is joined by Suzalee Blair-Gordon and Gordon Bedford, two members of the Genomics England’s Public Standing Group on the lifetime genome, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that helped to facilitate this work. Together, they consider the broader societal implications of lifetime genomic data, and how public involvement can help guide policy and practice in the UK and beyond. This conversation is part of our ongoing work through the Generation Study, exploring how genomics can be used responsibly and meaningfully from birth onwards. You can listen to some of our Generation Study episodes by following the links below. What can we learn from the Generation Study? How has design research shaped the Generation Study? What do parents want to know about the Generation Study? "This isn’t just a science project, it’s about designing a future where everyone feels included and protected. We need more voices, parents, young people, underrepresented communities, to keep shaping it in the right direction." You can download the transcript, or read it below. Harriet: Welcome to Behind the Genes. Suzalee: I have come to terms with the thought that life is unpredictable and I have already begun to accept any health condition that comes my way. Believe you me, I have been through the stage of denial, and yes, I have frozen upon hearing health diagnoses in the past but now I believe that I am a bit wiser to accept the things that I cannot change and to prepare to face the symptoms of whatever illness I am to be dealt with or to be dealt to me. If the analysis of my genome can help me to prepare, then yes, I am going to welcome this programme with open arms. Harriet: My name is Harriet Etheredge, and I am the Ethics Lead on the Newborn Genomes Programme here at Genomic England. On today’s episode I’m joined by 3 really special guests, Suzalee Blair and Gordon Bedford, who are members of Genomics England’s Public Standing Group on Lifetime Genomes, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that has helped us to facilitate this work. Today we’ll be discussing the concept of the lifetime genome. What do we mean when we say, ‘lifetime genome’? How can we realise the promise of the lifetime genome to benefit people’s healthcare whilst at the same time really appreciating and understanding the very real risks associated? How do we collectively navigate ethical issues emerging at this genomic frontier? If you enjoy today’s episode, we would really love your support. Please share, like and give us a 5-star rating wherever you listen to your podcasts. And if there’s a guest that you’d love to hear on a future episode of Behind the Genes, please contact us on [email protected]. Let’s get on with the show. I’ll start off by asking our guests to please introduce yourselves. Suzalee, over to you. Suzalee: Thanks, Harriet. So I am a proud mum of two kids, teacher of computing at one of the best academic trusts in the UK, and I am also a sickler, and for those who don’t know what that means, I am living with sickle cell disease. Harriet: Thank you so much, Suzalee. Gordon, over to you. Gordon: I’m Gordon Bedford, I’m a pharmacist based in The Midlands. I’ve worked in hospital and community pharmacy. I have a genetic condition, which I won’t disclose on the podcast but that was my sort of position coming into this as I’m not a parent of children, but it was coming in from my perspective as a pharmacist professional and as a member of society as well. Harriet: Thank you so much, Gordon. And, last but certainly not least, Suzannah. Suzannah: So, yes, Suzannah Kinsella. I am a social researcher at Hopkins Van Mil, and I had the pleasure of facilitating all of the workshops where we gathered together the Public Standing Group and working on reporting the outcome from our discussions, so delighted to be coming in from South London. Harriet: Thank you so much, everyone, and it’s such a pleasure to have you here today. So, many regular listeners

In this episode of Behind the Genes, we explore how ethical preparedness can offer a more compassionate and collaborative approach to genomic medicine. Drawing on insights from the EPPiGen Project, our guests discuss how creative storytelling methods, like poetry, have helped families and professionals navigate the complex emotional, ethical and practical realities of genomics. Our guests reflect on the power of involving patients and families as equal partners in research, and how this can lead to more inclusive, empathetic, and effective care. The conversation explores how ethics can be a tool for support, not just regulation, and how creating space for people to share their stories can have a lasting impact on healthcare delivery. Our host for this episode, Dr Natalie Banner, Director of Ethics at Genomics England is joined by Professor Bobbie Farsides, Professor of Clinical and Biomedical Ethics and Dr Richard Gorman, Senior Research Fellow, both at Brighton and Sussex Medical School, and Paul Arvidson, member of the Genomics England Participant Panel and the Dad's Representative for SWAN UK. Paul shares his poem 'Tap tap tap' from the Helix of Love poetry book and we also hear from Lisa Beaton and Jo Wright, both members of the Participant Panel. "The project gave us the tools to find a different way to get at all of those things inside of all of us who were going through that experience... It’s almost like a different lens or a different filter to give us a way to look at all those things, almost like a magnifying lens; you can either hold it really close to your eye and it gives you like a blurry view of the world that goes on and you can relax behind that and find a way to explore things in a funny way or an interesting way, but you can also go really close into the subject and then you’ve got to deal with the things that are painful and the things that are difficult and the things that have had an impact." You can download the transcript, or read it below. Natalie: Welcome to Behind the Genes. Bobbie: In an earlier conversation with Paul, he used the word ‘extractive,’ and he said that he’s been involved in research before, and looking back on it he had felt at times it could be a little bit extractive. You come in, you ask questions, you take the data away and analyse it, and it might only be by chance that the participants ever know what became of things next. One of the real principles of this project was always going to be co-production and true collaboration with our participants. Our participants now have a variety of ways in which they can transport their voices into spaces that they previously found maybe alienating, challenging, and not particularly welcoming. Natalie: My name is Natalie Banner, I’m the Director of Ethics at Genomics England and your host on today’s episode of Behind the Genes. Today I’ll be joined by Paul Arvidson, a member of the participant panel at Genomics England, Professor Bobbie Farsides, Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School, and Dr Rich Gorman, Senior Research Fellow, also at Bright and Sussex Medical School. Today, we’ll be exploring the ethical preparedness in genomic medicine or EPPiGen Project. This project examined how the promise and challenges of genomic medicine are understood and experienced by the people at the heart of it, both the clinicians providing care and the patients and families involved. A big part of the EPPiGen Project explored using creative methods of storytelling and poetry to explore the experiences of parents of children with rare genetic conditions. We’ll discuss why the idea of ethical preparedness is crucial in genomic medicine to acknowledge the challenges and uncertainties that often accompany the search for knowledge and treatment in genomic healthcare, and to help professionals develop the skills to navigate the complex ethical considerations. If you enjoy today’s episode we’d love your support. Please like, share and rate us wherever you listen to your podcasts. Is there a guest you’d really like to hear on a future episode? Get in touch at [email protected]. So, I’m going to ask our fantastic guests to introduce themselves. Paul, would you like to go first? Paul: Hi, I’m Paul Arvidson. As well as my Genomics England hat, I’ve got a SWAN hat as well, I’m the dads’ rep for SWAN UK, and I’m on the poets from the EPPiGen Project. Natalie: Brilliant to have you hear today. Thanks, Paul. Rich? Rich: Hi, I’m Rich Gorman, I’m a Senior Research Fellow at Brighton and Sussex Medical School and I’ve been working on some of the research on the EPPiGen Project that looks at people’s social and ethical experiences of genomic medicine, and particularly families’ lived experiences of genomics. Natalie: Brilliant. Really looking forward to hearing from you. And Bobbie? Bobbie: Hello, I’m Bobbie Farsides, I’m Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School

As of February 2025, the Generation Study has recruited over 3,000 participants. In this episode of Behind the Genes, we explore what we have learnt so far from running the study and how it continues to evolve in response to emerging challenges. The conversation delves into key lessons from early recruitment, the challenges of ensuring diverse representation, and the ethical considerations surrounding the storage of genomic data. Our guests discuss how ongoing dialogue with communities is helping to refine recruitment strategies, improve equity in access, and enhance the diversity of genomic data. Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Alice Tuff-Lacey, Program Director for the Generation Study; Dalia Kasperaviciute, Scientific Director for Human Genomics at Genomics England; and Kerry Leeson Bevers, CEO of Alström Syndrome UK. For more information on the study, visit the Generation Study website, or see below for some of our top blogs and podcasts on the topic: Podcast: What do parents want to know about the Generation Study? Podcast: How has design research shaped the Generation Study? Blog: What is the Generation Study? "We always have to remember, don’t we, that if people say no to these things, it’s not a failure to on our part, or a failure on their part. It’s just something they’ve thought about and they don’t want to do, and for all sorts of different reasons. And the other reflection I have about different communities is the ‘different’ bit, is that what approach works for one community may not work for another, and I think that that’s something that’s going to have to evolve over length of the study, is finding the things that are the right way, the most helpful way to approach people." You can download the transcript, or read it below. Vivienne: Hello and welcome to Behind the Genes. Alice: “And this is quite an exciting shift in how we use whole genome sequencing, because what we are talking about is using it in a much more preventative way. Traditionally, where we’ve been using it is diagnostically where we know someone is sick and they’ve got symptoms of a rare condition, and we’re looking to see what they might have. What we’re actually talking about is screening babies from birth using their genome, to see if they are at risk of a particular condition, and what this means is this raising quite a lot of complex ethical, operational, and scientific and clinical questions.” Vivienne: My name’s Vivienne Parry, and I’m Head of Public Engagement here at Genomics England, and I’m your host on this episode of Behind the Genes. Now, if you are a fan of this podcast, and of course you’re a fan of this podcast, you may have already heard us talking about the Generation Study, the very exciting Genomics England research project which aims to screen 100,000 newborn babies for over 200 genetic conditions using whole genome sequencing. Well, we’ve got more on the study for you now. What we’re doing to make it both accessible and equitable for all parents-to-be, and our plans to ensure that we continue to listen to parents, and perhaps in future, the babies as they grow up. We’ll chat, too, about emerging challenges and how we might deal with them. I’m joined in our studio by Alice Tuff-Lacey, the Programme Director for the Generation Study, and Dalia Kasperaviciute, Scientific Director for Human Genomics, both from Genomics England, and we’re delighted to welcome Kerry Leeson-Bevers, Chief Executive of Alström Syndrome UK. And I’m just going to quickly ask Kerry, just tell us about Alström Syndrome and how you’re involved. Kerry: Yes, so Alström Syndrome is an ultra-rare genetic condition. My son has the condition and that’s how I got involved. So, the charity has been around now since 1998, so quite a well-established charity, but as part of our work we developed Breaking Down Barriers, which is a network of organisations working to improving engagement and involvement from diverse, marginalised and under-served communities as well. Vivienne: And you wear another hat as well? Kerry: I do. So, I’m also a member of the research team working on the process and impact evaluation for the Generation Study. So, I’m Chair of the Patient and Public Involvement and Engagement Advisory Group there. Vivienne: Well, the multiply hatted Kerry, we’re delighted to welcome you. Thank you so much for being with us. So, first of all, let’s just have a sense from Alice Tuff-Lacey about this project. In a nutshell, what’s it all about, Alice? Alice: Thanks Viv. So, I think in the last few years we’ve seen some really big advances in the diagnoses of rare diseases through things the Genomic Medicine Service. But we know it takes about 5 years often to diagnose most of these rare conditions. What we also know is that there are several hundred of them that are treatable, and actually there can be massive benefits to the child’s health from diagnosing and treating them earlier. I thin

Rare condition research is evolving, and patient communities are driving the breakthrough. In this special Rare Disease Day episode, we explore the challenges and opportunities shaping the future of rare condition therapies. From groundbreaking gene therapy trials to the power of patient-driven research, our guests discuss how collaboration between families, clinicians, researchers, and regulators is paving the way for faster diagnoses, equitable access to treatments, and innovative approaches like nucleic acid therapies and CRISPR gene editing. With insights from Myotubular Trust, we follow the journey of family-led patient communities and their impact on advancing gene therapy for myotubular myopathy - showcasing how lived experience is shaping the future of medicine. However, while patient-driven initiatives have led to incredible progress, not every family has the time, resources, or networks to lead these research efforts. Our guests discuss initiatives like the UK Platform for Nucleic Acid Therapies (UPNAT), which aims to streamline the development of innovative treatments and ensure equitable access for everyone impacted by rare conditions. Our host Dr Ana Lisa Tavares, Clinical lead for rare disease at Genomics England, is joined by Meriel McEntagart, Clinical lead for rare disease technologies at Genomics England, Anne Lennox, Founder and CEO of Myotubular Trust and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at University of Oxford. "My dream is in 5 to 10 years time, an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested. And at that exact time, the day of the diagnosis becomes also a day of hope, in a way, where immediately the researcher that sent the genetics lab flags that specific variant or specific mutations. We know exactly which is the best genetic therapy to go after." You can download the transcript, or read it below. Ana Lisa: Welcome to Behind the Genes. [Music plays] Anne: What we’ve understood is that the knowledge and experience of families and patients is even more vital than we’ve all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family, they would tell you, “Yes, my son has had the odd liver result.” There were some very serious liver complications but everybody thought that was a minor issue, but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing. [Music plays] Ana Lisa: My name is Ana Lisa Tavares, I’m Clinical Lead for Rare Disease research at Genomics England and your host for this episode of Behind the Genes. Today I’m joined by Anne Lennox, Founder and CEO of the Myotubular Trust, Dr Meriel McEntagart, an NHS consultant and Clinical Lead for Rare Disease Technologies at Genomics England, and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at the University of Oxford. Today we’ll be hearing about the importance of involving the patient community, particularly as new rare therapies are developed, and discussing the forward-facing work that’s happening that could have potential to unlock novel treatments for many rare conditions. If you enjoy today’s episode we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. Thank you so much for joining me today. Please could you introduce yourselves. Anne: I’m Anne Lennox, I’m one of the founders of the Myotubular Trust, a charity that raises research funds for and supports families affected by the rare genetic neuromuscular disorder myotubular myopathy. Meriel: I’m Meriel McEntagart, I’m a consultant in clinical genetics in the NHS and I have a special interest in neurogenic and neuromuscular conditions. Carlo: Hi, I’m Carlo Rinaldi, I’m Professor of Molecular and Translational Neuroscience at the University of Oxford. I’m a clinician scientist juggling my time between the clinic and the lab where we try to understand mechanisms of diseases to develop treatments for these conditions. And I’m also here as a representative of the UK Platform for Nucleic Acid Therapies, UPNAT. Thanks for your invitation, I’m very pleased to be here. Ana Lisa: Thank you. Meriel, I’d love you to tell us a bit about your work and how you met Anne, how did this story start? Meriel: Thank you. Well prior to being a consultant in clinical genetics, I spent 2 years as a clinical research fellow in neuromuscular conditions, and as part of that training I worked on a project where the gene for myotubular myopathy had just been identified, and so there was a big international effort to try and come up with sort of a registry of all the genetic variants that had been found as well as all the clinical symptoms that the affected patients had,

In this episode, our guests explore the impact of genetic discoveries on inherited retinal dystrophies, in particular retinitis pigmentosa (RP). The discussion highlights a recent study that identified two non-coding genetic variants linked to RP, predominantly in individuals of South Asian and African ancestry. The conversation highlights how advances in whole genome sequencing are uncovering previously hidden causes of genetic disease, improving diagnostic rates, and shaping the future of patient care. It also addresses the challenges faced by individuals from diverse backgrounds in accessing genetic testing, including cultural barriers, awareness gaps, and historical underrepresentation in genomic research. Our host Naimah Callachand is joined by researcher Dr Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, a patient representative diagnosed with retinitis pigmentosa and Founder and Chair of BAME Vision. We also hear from Martin Hills, an individual diagnosed with autosomal dominant retinitis pigmentosa. To access resources mentioned in this episode: Access the Unlock Genetics resource on the Retina UK website Visit the BAME vision website for more information and support Find out more about the groundbreaking discovery of the RNU4-2 genetic variant in the non-coding region which has been linked to neurodevelopmental conditions in our podcast episode "Discoveries like this lead to better clinical management. We understand better the progression of the disease when we can study this in many individuals from a wide spectrum of ages and different backgrounds. We can provide counselling as Bhavini was talking about. We can provide patients with a better idea of what the future may hold for their eye disease, and potentially, you know, we are all aiming towards being able to develop therapies for particular genes and particular diseases." You can download the transcript or read it below. Naimah: Welcome to Behind the Genes. Bhavini: The few common themes that always come out is that people don’t really understand what genetic testing and counselling is. They hear the word counselling, and they think it is the therapy that you receive counselling for your mental health or wellbeing. There is already a taboo around the terminology. Then it is lack of understanding and awareness or where to get that information from, and also sometimes in different cultures, if you have been diagnosed with sight loss, you know blindness is one of the worst sensory things that people can be diagnosed with. So, they try and hide it. They try and keep that individual at home because they think they are going to have an outcast in the community, in the wider family, and it would be frowned upon). Naimah: My name is Naimah Callachand and I am Head of Product Engagement and Growth at Genomics England. I am also one of the hosts of Behind the Genes. On today’s episode I am joined by Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, patient representative. Today we will be discussing findings from a recently published study in the American Society of Human Genetics Journal which identified two non-coding variants as a cause of retinal dystrophy in people commonly of South Asian and African ancestry. If you enjoy today’s episode, we’d love your support. Please like, share, and rate us on wherever you listen to your podcasts. Okay, so first of all I would like to ask each of the three of you to introduce yourselves. Bhavini, maybe we’ll start with you. Bhavini: Hi, I’m Bhavini Makwana, patient representative, and also Chair of BAME Vision. I have other roles where I volunteer for Retina UK, and I work for Thomas Pocklington Trust. Naimah: Thanks Bhavini. Gavin. Gavin: Hi, my name is Gavin Arno, I am Associate Director for Research at the Greenwood Genetic Centre in South Carolina, and I am Honorary Associate Professor at the UCL Institute of Ophthalmology in London. Naimah: Thanks Gavin. And Kate. Kate: Hi, I’m Kate Arkell, Research Development Manager at Retina UK. Naimah: Lovely to have you all today. So, let’s get into the conversation then. So Gavin, let’s come to you first. First of all, what is retinitis pigmentosa and what does it mean to have an inherited retinal dystrophy? Gavin: So, retinitis pigmentosa is a disorder that affects the retina at the back of the eye. It is a disease that starts in the rod photoreceptor cells. So, these cells are dysfunctional and then degenerate causing loss of peripheral and night vision initially, and that progresses to include central vision and often patients will go completely blind with this disease. So, retinal dystrophies are diseases that affect the retina. There are over 300 genes known to cause retail dystrophy so far, and these affect different cells at

In this episode, our guests discuss the potential of large-scale health datasets to transform research and improve patient outcomes and healthcare systems. Our guests also delve into the ethical, logistical, and technical challenges that come with these programmes. We hear how organisations such as UK Biobank, Our Future Health, and All of Us are collecting rich, diverse datasets, collaborating and actively working to ensure that these resources are accessible to researchers worldwide. Hosting this episode is Dr Natalie Banner, Director of Ethics at Genomics England. She is joined by Dr Raghib Ali, Chief Medical Officer and Chief Investigator at Our Future Health, Professor Naomi Allen, Professor of Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Chief Scientist for UK Biobank, and Dr Andrea Ramírez, Chief Data Officer at the All of Us Research Program in the United States. "There are areas where academia and the NHS are very strong, and areas where industry is very strong, and by working together as we saw very good examples during the pandemic with the vaccine and diagnostic tests etc, that collaboration between the NHS and academia industry leads to much more rapid and wider benefits for our patients and hopefully in the future for the population as a whole in terms of early detection and prevention of disease." You can download the transcript or read it below. Natalie: Welcome to Behind the Genes Naomi: So, we talked to each other quite regularly. We have tried to learn from each other about the efficiencies of what to do and what not to do in how to run these large-scale studies efficiently. When you are trying to recruit and engage hundreds of thousands of participants, you need to do things very cost effectively. How to send out web-based questionnaires to individuals, how to collect biological samples, how the make the data easily accessible to researchers so they know exactly what data they are using. All of that we are learning from each other. You know, it is a work in progress all the time. In particular you know, how can we standardise our data so that researchers who are using all of us can then try and replicate their findings in a different population in the UK by using UK Biobank or Our Future Health. Natalie: My name is Natalie Banner, and I am Director of Ethics at Genomics England. On today’s episode we will be discussing how we can unlock the potential of large health datasets. By that I mean bringing together data on a massive scale, including for example genomic, clinical, biometric, imaging, and other health information from hundreds and thousands of participants, and making it available in a secure way for a wide range of research purposes over a long time period. Through collaboration and industry partnerships, these programmes have the potential to transform research and deliver real world benefits for patients and health systems. But they also come with challenges ranging from issues in equity and ethics through to logistics, funding, and considerable technical complexities. If you enjoy today’s episode, we would love your support. Please like, share, and rate us on wherever you listen to your podcasts. I’m delighted to be joined today by 3 fantastic experts to explore this topic. Dr Raghib Ali, Chief Medical Officer and Chief Investigator at Our Future Health. Professor Naomi Allen, Professor of Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Chief Scientist for UK Biobank, and Dr Andrea Ramírez, Chief Data Officer at the All of Us Research Program in the United States. Andrea, if I could start with you. It would be really great to hear about All of Us, an incredibly ambitious programme in the US, and maybe some of the successes it has achieved so far. Andrea: Absolutely. Wonderful to be here with you and thank for you for the invitation. The All of Us Research Program started in 2016 from the Precision Medicine Initiative and was funded with the goal of recruiting 1 million or more participants into a health database. That includes information not only from things like biospecimens including their whole genome sequence, but also surveys that participants provide, and importantly linking electronic health record information and other public data that is available, to create a large database that researchers that access and use to study precision health. We have recruited over 830,000 participants to date and are currently sharing available data on over 600,000. So, we’re excited to be with your audience, and I hope we can learn more and contribute to educating people listening about precision medicine. Natalie: Thank you, Andrea. And not that this is competitive at all, but Raghib, as we are recording this, I understand the Our Future Health programme is marking quite a phenomenal milestone of 1 million participants. Would you mind telling us a little bit about the programme and something that you se

In this explainer episode, we’ve asked John Pullinger, Senior Bio Sample Operations Manager at Genomics England, to explain what it means to go on a diagnostic odyssey. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. The episodes mentioned in the conversation are linked below. Hope for those with no primary findings The impact of a genetic diagnosis on mental health You can download the transcript or read it below. Florence: What does it mean to go on a diagnostic odyssey? I'm joined by John Pullinger, Senior Bio Sample Operations Manager for Genomics England to find out more. So, John, first of all, can you explain what we mean by diagnostic odyssey? John: Yes, of course. The diagnostic odyssey is a term used to describe the journey that many people with rare conditions and their families undertake to receive an accurate diagnosis, a journey that takes on average over five and a half years. The rarity of the condition means that there are few, if any, other people affected by it, for doctors to draw their experience from. Some individuals might never receive a diagnosis. My job involves making sure that samples sent through the Genomics England processes can travel smoothly from the NHS hospitals to be sequenced and the results be reported back to the individual. We try and minimise the amount of time that samples and associated data is in our care. Florence: And for people listening who might not know, could you explain why it sometimes takes a long time for people to receive a diagnosis? John: There are estimated to be over 7,000 rare conditions. This means that healthcare professionals may not be familiar with all of them and so may not recognise them or know how to test for them. In addition to this, some conditions affect multiple parts of the body. For example, skin, the heart, and the lungs. In these cases, there will be a need to visit specialists from multiple departments, and each will be looking specifically at their own area. This could lead to referral loops where the patient needs to consult multiple healthcare professionals, all of which contributes to the time taken to receive a diagnosis. Since, for the majority of rare conditions, there is an underlying genetic cause. This means that most individuals who get a diagnosis will receive one through genomic testing, whether that be whole genome sequencing as offered here at Genomics England, or more targeted panel testing. Typically testing will identify a particular gene, which is known to be linked to a specific condition. For certain conditions, it requires a real expert in the condition to even think about testing for it. Sometimes a condition will present in a way that is different to most other people who have it. So they may have symptoms that others don't. This also adds to the buildup of time taken to receive the diagnosis. Florence: So, you mentioned earlier, John, that the diagnostic odyssey lasts an average of five and a half years. Can you explain what kind of effect this long waiting time has on individuals and their families? John: Absolutely. One aspect of the diagnostic odyssey that is important to recognise is the physical effect of the as yet undiagnosed condition that's present and affecting the individual and their family on a daily basis. Those with rare conditions may be affected by a range of emotions connected to the ongoing journey that they're on, including feelings of isolation. Also stress and anxiety. The fear of unknown can have a massive knock-on effect on the mental health of the individual and their family. And it's important to recognise the signs of this so that people can take steps to manage their mental health. Many rare conditions first present themselves in children and young adults, so considering the effects on their day-to-day lives is especially important. Florence: If you'd like to learn more about how the diagnostic odyssey can affect someone, listen to our previous podcast, “Hope for those with no primary findings”, where Participant Panel member Lisa Beaton, shares her experience of awaiting a diagnosis for her daughter. And so, John, can we talk now about what happens at the end of a diagnostic odyssey? John: A section of the odyssey that is essential to understand is potentially getting a diagnosis. It may come as a surprise to think that the diagnosis can sometimes be scary as well as a potential relief to the family and also the individual involved. But this reason the work of genetic counsellors is crucial to help those with rare conditions, understand and adapt to the medical, psychological, and potential reproductive implications of their new diagnosis. Florence: Our previous podcast, “The impact of a genetic diagnosis on mental health” covers this topic in much more

The Genetic Rare Syndromes Observational Cohort (GenROC) study aims to improve our understanding of how rare genetic conditions affect the way children grow, their physical health and their development. Through actively involving parents as experts in their child's condition, the study seeks to gather valuable insights and ensure that family experiences shape future research and care strategies. You can find out more about the study and eligibility criteria via the Bristol University website. In this episode, Jillian Hastings Ward, patient advocate and former Chair of the Participant Panel at Genomics England, is joined by Dr Karen Low, a clinical geneticist leading the study at the University of Bristol, who shares insights into its objectives, the importance of a co-production approach with families, and the vital data being collected in the study to improve support for these children and their families. We'll also hear from Lindsay Randall, a parent who discusses the journey of receiving a rare diagnosis for her child, highlighting the critical need for more comprehensive information and community support. "If you join GenROC, that data will be used to develop a growth chart for your child essentially and their genetic condition, so I’m really excited about it because I feel like that’s a very concrete definite given now for all the families in GenROC, which is just brilliant." You can download the transcript or read it below. Jillian: Welcome to Behind the Genes Lindsay: Historically, there’s been a significant absence of patient voice in rare disease research and development, and knowing that’s changing, I think that’s really empowering for families and to know that professionals and industry are actually listening to our stories and unmet needs and really trying to understand, and that offers much greater impact on the care and treatments of patients in the future. Jillian: My name is Jillian Hastings-Ward. On today’s episode I’m joined by Dr Karen Low, Consultant Clinical Geneticist and Chief Investigator for the General Cohort Study, and Lindsay Randall, Paediatric Practice Development Nurse and founder of Arthur’s Quest, which is a UK registered, non-profit, raising awareness for the ultra-rare condition: SLC6A1, developmental and epileptic encephalopathy. Welcome to you both. Today we’ll be discussing the GenROC study, which is aiming to understand more about the health, development and valuing the experiences of children with neurodevelopmental conditions. If you enjoy today’s episode we’d love your support. Please like, share, and rate us on wherever you listen to your podcasts. Thank you both very much for joining us today, Karen and Lindsay. There’s a lot we want to cover, but first of all it would be great just to put a little bit of context around the Gen-Roc study. Karen, can you tell us a bit about what the study is aiming to do, who is eligible and why do you want them? Karen: Thank you. And thank you so much for having me today, Jillian. So, the GenROC study, first to just explain to people what ‘GenROC’ stands for. GenROC stands for the Genetic Rare Syndromes Observational Cohort Study. Just to give you some context about the study, I’m a clinical geneticist and most of my clinical work focuses on paediatrics, so I see children in my clinics and the sort of children I see generally are children with rare genetic syndromes. The last five to ten years we’ve got much better at diagnosing children with these rare conditions and that’s because testing has got so much better. We can now do whole genome sequencing and we can do that on the NHS, which is amazing, children can get their tests as part of their clinical care, so it means that a lot more children are being diagnosed with rare conditions, about 2,000 per year in the UK. And the thing about that is, that I see these children in my clinics and I give their families that diagnosis. But the problem is for so many of these ultra-rare conditions, like Lindsay’s family has, we sit there and we say to the family, “Well, your child has got ‘X’ condition,” and we give them some information from maybe one or two publications and linked to a leaflet and a Facebook group. And then we say, “But really we don’t know that much about this condition.” And they say, “But what is it going to mean for them when they are growing up or when they are adults? Will they be able to finish school? Will they be able to work? What is it going to mean?” And I have to shrug my shoulders and go, “I’m not really sure.” And as a geneticist and as a doctor and as a mother really, I just felt that wasn’t good enough, and I found it really frustrating and I know that the families that I work with, that I look after, also find it frustrating and I wanted to do better. And I also found it frustrating that for many genes, researchers would publish two or maybe three publications about these conditions, and then they would move on to the next novel gene, and actually, the j

As 2024 comes to a close, we take a moment to reflect on what has been a busy year at Genomics England and in the wider genomics community. Throughout the year, guests have joined us to discuss groundbreaking research discoveries, important ethical considerations, and share their personal stories. It was also a year of transformation: we rebranded our podcast as Behind the Genes, welcomed Dr Rich Scott as our new Chief Executive Officer, and launched the Generation Study, in partnership with NHS England. The Participant Panel also saw changes, with Kirsty Irvine stepping into the role of Chair and Adam Clatworthy and Helen White becoming Vice Chairs. In this special end of year episode, Adam Clatworthy, Vice-Chair of the Participant Panel, sits down with Dr. Rich Scott, CEO of Genomics England, to look back on the highlights of 2024. Together, they revisit key podcast moments, reflect on research discoveries, and share insights into the evolving world of genomics. Below are the links to the podcasts mentioned in this episode, in order of appearance: Celebrating genomic breakthroughs - Insights from the Festival of Genomics Shining a light on rare conditions How has a groundbreaking genomic discovery impacted thousands worldwide? How can we work in partnership towards a new era of genomic medicine and research? How has design research shaped the Generation Study? How can we bridge the gap between diverse communities? Can Artificial Intelligence accelerate the impact of genomics? "It's really important that we just continue to bring that patient and participant community on that journey, just to ensure that they really understand the full benefits. And we've talked about that on the episode today. I know that the panel has always encouraged the Genomics England team to look at its boots while shooting for the moon. I really like that phrase just to make sure, look, we can't forget where we've come from to make sure we're taking people on that journey" You can download the transcript or read it below. Adam: Welcome to Behind the Genes. Rich: Our vision at Genomics England is a world where everyone can benefit from genomic healthcare, thinking about how we ensure the lessons we’ve learnt through our diverse data programme is embedded across all of our work. So that word “everyone” applies to people in lots of different ways, different communities people come from, different socioeconomic backgrounds, making sure that equity is baked into all of our work. And there’s real opportunity for genomics to play a broader role than in rare conditions and in cancer, we’re proud of the impact we’re already having there, and we should really look to the future. Adam: My name is Adam Clatworthy, and I’m the Vice-Chair for rare conditions on the Participant Panel at Genomics England. On today’s episode, I’m going to be joined by Rich Scott, CEO of Genomics England. We’re going to be taking a look back at the key milestones from 2024 for Genomics England, and really discussing our hopes and aspirations for the year ahead. During this episode we’ll also hear from some of our guests we’ve had on the show this year, who have helped shape our discussions and shared some of their most impactful moments and insights. And if you’d like to listen to more like this, then please subscribe to Behind the Genes on your favourite podcast app. So, with that, thanks for joining me, Rich, how are you doing? Rich: I’m great, thanks for hosting today, I’m really excited about it. Adam: So, Rich, it’s been a pretty exciting year for you, you’ve taken on the CEO role at Genomics England full-time, so why don’t you just start by telling us about how those first few months have been for you? Rich: It’s been a really exciting year, I think for us overall at Genomics England, and obviously personally taking on the CEO role, which is an enormous privilege. I’ve been at Genomics England nine years, and I think both a privilege and a real responsibility to take on the role. To think both about how we continue to honour the commitments we’ve given our participants and those we work with, and to think about the future, where we might go together, what evidence we need to generate, what our systems need to support. So it’s been great taking on the role, and thinking about that, both the present and the future, and there’s been lots, as we’ll talk about, there’s been lots going on. Adam: No, that’s great. And I must say for myself as well, I started the Vice-Chair role at a very similar time to you early in the year. When I started, we were in the process of looking for our next Chair. Obviously, we had Jillian and Rebecca, both standing down, after many years in the role. They’ve been there from the start, really guiding the Panel through this amazingly successful period. But for me, I’ve really enjoyed working in partnership with Helen, who is our Vice-Chair for cancer. It’s been a real partnership, in terms of filling in for that interim leadership role.

In this explainer episode, we’ve asked Katrina Stone, Clinical Genetics Doctor, and Clinical Fellow at Genomics England, to explain what happens when you go for whole genome sequencing for a rare condition. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Florence: What happens when I go for whole genome sequencing? I'm joined by Katrina Stone, Clinical Genetics Doctor, to find out more. So, Katrina, first things first. What is the purpose of whole genome sequencing? Katrina: The purpose of whole genome sequencing is to try to make a precise genetic diagnosis for someone with a suspected or confirmed genetic condition. Florence: And why might someone get whole genome sequencing? Katrina: They might get whole genome sequencing because they are known to have a condition which is likely to be genetic, but the medical team wants to find out what the exact genetic cause is. In other cases, the diagnosis might not be known, and the reason for doing whole genome sequencing is to find out whether there is a genetic condition present. Some of the benefits of having the test is that. If a condition is identified, this can provide an explanation for the family about what's been going on, and it can also bring to an end further unnecessary investigations. Also, if a genetic diagnosis is confirmed, this can sometimes point towards other things which might need to be kept an eye on for the individual. In addition, once a diagnosis is confirmed, a doctor can advise the family on the likelihood of other members of the family or future children being affected with the same condition, and they can use this information to help with future family planning. Florence: So, then what happens when a person physically goes to get the test? Katrina: In most cases, an individual will see a specialist doctor. This might be a genetics doctor, but it could be a doctor specialising in another body system. They'll do a full assessment of the individual, including finding out lots of information about them and their family, and also examining them to look for any clues that might point towards a specific genetic diagnosis. Once the family have decided to go ahead with the test, their consent will be taken, where the test will be explained in more detail, including the pros and cons of going ahead with the test and after that samples can be taken. Usually this is a blood sample, but occasionally a saliva sample or cheek swab could be taken. The best way to perform whole genome sequencing is with a sample from the person being tested along with both of their parents. And the reason for this is that it makes it easier to separate out genetic changes that are more likely to be significant from those that just represent harmless genetic variation what makes us all unique. Florence: What happens to this sample after the test has taken place? Katrina: So, the blood samples will go to a genetics lab where the genetic material known as DNA is extracted. The DNA is then sequenced, so we get an electronic file of all their genetic information. This is then analysed firstly by a computer which picks out changes or variants in their DNA, which are more likely to be significant. After this, a trained clinical scientist analyses the data in detail. Sometimes there isn't a clear-cut result, and the scientists might need help from others and interpreting the result, but if there is, they can create a report which details the likely diagnosis. Florence: And finally, how will the patient get the result from their whole genome sequencing test? Katrina: Usually, the result is fed back to the patient and their family by the clinician who arranged their testing or one of their close colleagues. It's important to note that not everyone will get a genetic diagnosis from the test. This doesn't necessarily mean there isn't a genetic diagnosis present. There are several reasons why tests might be negative. One is that no test is perfect and something important might have been missed because of the way the test works. Or it may be that the person being tested has a change in a gene that hasn't been described as causing a disease before, so we wouldn't even know to look for it. There's also a possibility that there isn't a single genetic cause for their symptoms. Rather, lots of minor genetic factors are causing their condition. We're not very good at testing for these yet. Finally, there could be a non-genetic cause that just hasn't been identified yet. One of the benefits of having a whole genome sequencing test is that the data can be stored and looked at again in the future, either in light of new evidence or once our knowledge of genetics has improved. Florence: That was Katrina Stone explaining

In this episode, we explore the importance of patient involvement in shaping rare condition research initiatives. Our guests discuss why it’s crucial to involve individuals with lived experiences, including patients and caregivers, in setting research agendas. In doing so, this approach ensures research can be more inclusive, efficient, and impactful, addressing the issues that matter most to those affected. Mel Dixon, Founder Cure DHDDS and member of Genomics England Participant Panel is joined by Jo Balfour, Founder of CamRARE and Dr Rona Smith, Senior Research Associate at the University of Cambridge and Honorary Consultant in Nephrology and Vasculitis. Find out more about the Cambridge Rare Disease Research Network, discussed in the episode, which aims to support the rare condition community in building an online network of partnerships and resources to facilitate new patient-centred research opportunities. "We’re really turning research on its head, moving away from it being a researcher-led activity where they decide on the idea and the research concept and bring patients in at different points along that research journey and instead starting with the patient’s idea in the first place. It can only be a better system for all because it improves efficiency, it improves potentially the long term outputs and, most importantly, outcomes for patients." You can download the transcript or read it below. Mel: Welcome to Behind the Genes. Rona: I think it really means that we measure what matters to patients and individuals that are affected. Often, it’s really difficult to capture kind of the real impact of disease and there’s a tendency for researchers to measure things that are easy to measure and are reproducible, which of course is important but what’s most important is actually being able to truly capture the impact of an intervention on an individual’s condition. So, I think that’s another key aspect of having people with lived experience involved right from the start. Mel: My name is Mel Dixon and I’m a member of the Participant Panel at Genomics England and founder of Cure DHDDS, a charity set up to raise awareness, support families and help drive research into the ultra-rare DHDDS gene variant. On today’s episode I’m joined by Jo Balfour, Managing Director of CamRARE, which is the Cambridge Rare Disease Network. This network unites patients, advocates, experts and leaders to address the challenges faced by people affected by rare conditions. I’m also joined by Rona Smith, Associate Professor at the University of Cambridge and honorary consultant in nephrology and vasculitis. Today we’ll be discussing the role of patients in setting research agendas and how their involvement can lead to more impactful and patient-centred research. If you enjoy today’s episode we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. Before we begin the interview I’d like to share a little bit of my story. In November 2022, following whole genome sequencing, we received the news that two of our three children carried a neurodevelopmental and neurodegenerative DHDDS genetic variant. At the time of our children’s diagnosis there was very little information on our gene, minimal research happening into it and no treatment pathway. Through our charity, Cure DHDDS, we have worked tirelessly to instigate research and create a collaborative scientific research community. I am a huge advocate for patient-led research and have witnessed first-hand the positive impact it can have on patient lives. Thanks to the work of the many scientists that we have had the honour of collaborating with, within two years of our children’s diagnosis we have a disease-modifying therapy in our sight and an ASO (Antisense oligonucleotides) therapy in development. We are incredibly grateful for the opportunities genetic testing has given us but I also appreciate how overwhelming a genetic diagnosis can be and how challenging it can be for families to initiate research projects with little to no resources, and that’s why initiatives such as CamRARE that we’ll be discussing today are so important. On that note, let’s get back to our podcast guests. I wonder before we dive into today’s topic if you could both give a brief introduction, and, Rona, if you could also give the less scientifically-minded of us an explanation about what nephrology is. Rona: Thank you for inviting me today. So I’m Rona Smith, I work in Cambridge and I’m a nephrologist and that means somebody that looks after individuals who have diseases that affect their kidneys. My specialist interest is in something called vasculitis which is a rare autoimmune disease that affects all organs in the body but kidneys as well. Mel: Thank you. And Jo? Jo: Hi Mel. I’m Jo Balfour, the Managing Director and one of the founding members of Cambridge Rare Disease Network, or CamRARE for short. I think we’re often described as the ‘Chief Everything Officers’. I man

In this explainer episode, we’ve asked Meriel McEntagart, Clinical Geneticist in the NHS and Clinical Lead for Rare Disease Technologies at Genomics England, to explain how genetic conditions can be inherited, and other ways they may arise. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. To learn more about X-linked inheritance, as mentioned in the episode, tune in to our explainer episode, how does X-linked inheritance work? You can download the transcript or read it below. Florence: Are genetic conditions always inherited from parents? I'm joined by Meriel McEntagart, clinical geneticist for the NHS to find out more. So, Meriel, first things first. How can a genetic change cause a condition? Meriel: We have about 20,000 genes. That's the estimate and they are the code or blueprint for how to grow and develop a human being. And, if you think about a code, you can have a mistake in a code or a variant in a code. And if that happens, such as one genetic letter being changed for another, the result can be that the code doesn't give the correct instructions about how to grow and develop that human being. There are lots of different ways in which those changes can happen. Florence: And how can we inherit conditions from our parents? Meriel: Well, for the most part, like I mentioned, we've got 20,000 pairs of genes and we get one of each pair from our mother and our father. And so, for lots of genetic conditions, they follow a pattern of inheritance where one copy of that pair of genes has got the variant or spelling mistake in it, which causes the condition. So just having a single mistake in that pair of genes is enough to cause you to develop the symptoms of the condition. Other conditions show where you only develop the condition if both copies of the pair, the one you get from your mother and the one you get from your father have got a variant or a spelling mistake in the gene. So, you actually don't have a working copy of that gene. There are other patterns of inheritance as well. And so, we talk about X-linked inheritance. That can arise because women have what we call two X chromosomes; men only have one X chromosome. Florence: If you want to learn more about X-linked Inheritance, you can check out our previous podcast. How does X-linked inheritance work? So then do parents who have a condition always pass it on to their children? Meriel: So, this is again, where we think about some of those patterns of inheritance that I've just mentioned. If somebody has a condition, for example, a dominant condition, they will have that variant or genetic change that's causing their condition in one of their pair of genes. So then it's 50:50 when they have a child, whether they pass on the gene that's carrying that variant or not, because the child will be getting the other copy of that pair from their partner. If they do inherit that copy with the variant in it, then they will develop the symptoms of the condition in most cases. In some situations, however, a parent can have a genetic condition. So, they develop symptoms of the condition, and as I've mentioned, it's 50:50, whether it gets passed onto the child, so the child could actually inherit that genetic variant, but potentially not show signs of the condition. And this is what we call ‘reduced penetrance’. This means you can carry a genetic variant and probably some other event has to take place to cause you to develop symptoms. So that might be that there's other genetic factors that you inherit that trigger you to develop symptoms or there might be an illness or something that you experience that brings out the expression of that gene. So that's quite an important, consideration when we're looking at genetic variants and whether somebody will develop symptoms. Florence: And finally, how do we develop conditions that don't come from our parents? Meriel: Well, I suppose the main explanation for that is what we call a de novo genetic event. So that can arise when we are conceived. So for example, genes get copied to be put into the sperm or our genes get copied to be put into the egg. And in that process of making the sperm and the egg, a spelling mistake or mutation can arise in the DNA and then that sperm or that egg, whichever one has it, takes that forward into making the baby. And then the baby from that point will have that genetic variant in every single cell in their body. So it hasn’t come from the parents, so it’s not inherited but it still is a genetic condition. This is something that now that we're able to do whole genome sequencing, we are finding is a more common explanation for developmental disorders or conditions in children than we previously appreciated. And quite a lot of conditions where the child has congenital abnorma

In this episode, we explore findings from a groundbreaking study recently published in Nature which revealed potential targets for bowel cancer prevention and treatment. The study provides the most detailed understanding yet of bowel cancer’s genetic makeup. The research, which used data from the 100,000 Genomes Project identified over 250 genes that play a crucial role in the condition, driver genes and potential drug targets. Our guests discuss the potential impact of these findings on patient outcomes, screening for bowel cancer, and future prevention strategies. Helen White, Participant Panel Vice-Chair for Cancer at Genomics England is joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University. "The people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldn’t benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what we’re seeking to realise now. But, you know, it’s not a given when we treat people in the clinic so we’re very, very grateful to those individuals." You can read more about the study in our colorectal cancer blog and our study findings news story. You can download the transcript or read it below. Helen: Welcome to Behind the Genes. Ian: One of the great hopes is that some of these new genes that we’ve found could be useful in preventing cancer and it doesn’t necessarily matter that they’re rare, even if they’re only 1% of cancers, by using those and changing those in the normal individual before they have had cancer then we may be able to reduce that risk. So, there are lots of potential new targets for prevention that are coming through. My name is Helen White and I’m the Participant Panel Vice-Chair for Cancer at Genomics England. Today I’m delighted to be joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University. Today we will be discussing a pioneering colorectal cancer study which using data from the 100,000 Genomes Project has uncovered new insights that could transform diagnosis and treatment for patients with bowel cancer. If you enjoyed today’s episode we would love your support, please like, share and rate us on wherever you listen to your podcast. Thank you for joining me today. We’re going to be discussing the findings from a landmark study that has been published in nature. This study used data generously donated by people with bowel cancer who took part in the 100,000 Genomes Project giving us the most detailed look yet at the genetic makeup of colorectal cancer better known as bowel cancer. But before we get into that let’s start by hearing from my guests. Could each of you please introduce yourselves. Ian: I’m Ian Tomlinson, I work at the University of Oxford and most of my work is research into bowel cancer, it’s genetic causes, the genes that are involved in actually causing the cancer to grow which may be different from genetic causes and also the use of that data to help patients whether guiding future treatments or potentially helping to prevent bowel cancer which would obviously be our optimum strategy to have the biggest impact on the disease and its incidents. Claire: So, I’m Claire Coughlan, I’m the clinical lead for Bowel Cancer UK and my remit at the charity is to ensure that everything we do is clinically relevant and that we’re providing services that meet the needs of those affected by bowel cancer and the educational needs of those health professionals that work with people affected by bowel cancer. I’m also a nurse consultant in colorectal cancer at Lewisham and Greenwich NHS Trust and I lead an urgent referral service there and also work with patients with late effects of bowel cancer. David: I’m David Church, I’m a medical oncologist and Cancer Research UK advanced clinician scientist at the University of Oxford. I treat bowel cancer clinically and do research on bowel cancer and womb cancer including a lot of research using samples and data from Genomics England data service we’re discussing today of course. Helen: Great, thank you. Now let’s turn to Claire to learn more about bowel cancer. Claire, can you share with us how common it is, how treatable it is and if there are any trends in terms of which groups of people are affected? Claire: Of course, bowel cancer is a relatively common cancer, there are about 46,000 people each year in the UK diagnosed with bowel cancer so that is quite a large number. The thin

In this explainer episode, we’ve asked Adrianto Wirawan, Director of Bioinformatics Engineering at Genomics England, to explain what the term 'no primary findings' means. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Florence: What does ‘no primary findings’ mean? I'm joined by Adrianto Wirawan, Director of Bioinformatics Engineering for Genomics England, to find out more. So firstly, Adrianto, when we speak about findings from genomic tests, what does this mean? What are we looking for when we do a genomic test? Adrianto: Our DNA is made up of a long sequence of letters that act like instructions for your body. Genomic testing analyses these letters to see if there are any unusual patterns or changes that might change your health. You can imagine your DNA as a book full of recipes for your body. Every recipe tells your body how to make proteins that keep you healthy, and sometimes there might be a typo in the recipe, like missing an ingredient or mixing up the steps. This could result in a health problem, just like how a changed recipe can lead to a bad dish. On average, we would expect about 5 million out of our 3 billion DNA letters to be different. And each of these, we call them a genetic variant. Genomic testing is designed to examine some of these variants to help inform our healthcare. So, for example, in understanding why certain health problems happen and in choosing the best treatment based on our unique genetic makeup. Florence: And what do we mean by primary findings? Adrianto: Primary findings mean that in a patient's genomic testing, we identified a set of variants that is linked to the patient's condition. The variants that we have makes us who we are. However, not all of them cause a disease or contribute to a health problem. our bioinformatics pipelines will automatically prioritise variants of potential relevance to the patient's conditions. Using this data, the NHS clinical scientists will then determine whether any of these prioritised variants are linked to the patient's condition and whether a genetic diagnosis has been identified, which would explain why certain health problems happen. Florence: So, then what happens when there are no primary findings? Adrianto: When no primary findings are found, that means that no genetic diagnosis has been identified. As developments are made and our knowledge of the variance improves over time, additional findings might be identified in the future. The clinical team responsible for a patient's care may request reanalysis of data according to the national guidance, following a change in the patient's clinical status to inform reproductive decisions, or after significant new disease gene associations have emerged. In addition, Genomics England also provides the diagnostic discovery pathway where we focus on uncovering new diagnosis, where the participants of the 100,000 Genomes Project, as well as the patient's sequenced through the NHS Genomic Medicine Service This is meant to be more equitable as we don't rely on the clinical teams to raise individual separate requests. Florence: And finally, what do we mean by secondary findings? Adrianto: Secondary findings are additional findings not related to the conditions in which the patient was recruited for. For example, if a patient was recruited for one type of cancer, but perhaps we found variants linked to a different condition. We explored secondary findings for the 100,000 Genomes Project but we do not do secondary findings for the Genomic Medicine Service. Florence: That was Adrianto Wirawan explaining what we mean by ‘no primary findings’. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.

In this explainer episode, we’ve asked Mathilde Leblond, Senior Design Researcher for the Generation Study at Genomics England, to answer some frequently asked questions that we received from parents who we engaged with for the design of the study. You can hear more information about Generation Study via the study's official website and in our previous podcast episodes: How has design research shaped the Generation Study? Which conditions will we look for initially in the Generation Study? You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Naimah: You may have heard about the Generation Study. This research study led by Genomics England in partnership with NHS England will sequence the whole genomes of a hundred thousand newborn babies and will look for more than 200 rare conditions that could be treated in the NHS in early childhood. The study seeks to improve how we diagnose and treat rare genetic conditions to enable babies and families to have better outcomes. Today I'm joined by Mathilde Leblond, who leads design research for the Generation Study, and will be answering some of the frequently asked questions that we receive from parents who we engaged with for the design of the study — the same questions that expectant parents at participating hospitals might have before deciding if they want to take part. So first of all, Mathilde, can you tell me a little bit more about your role? Mathilde: Hello. So, I'm a design researcher. My role is to support my colleagues, understand our users deeply so that we can create experiences that are as positive and seamless as possible. So today we'll talk about the parents who are the ones invited to take part in the Generation Study, but our users also include the midwives who are approaching them and taking blood samples. The clinical scientists who are interpreting the results and the specialist paediatricians will be contacting the parents if a condition is suspected, and even many more users actually. So, we did a lot of research prior to launching to shape the Generation Study, and now that we're live, we continue doing more to keep improving the experience. Naimah: Okay, so can you give us a bit of background? How did you engage with parents in this study? Mathilde: Yeah, so today we've involved over 150 pregnant and recent parents in our co-design sessions. And these sessions were slightly different each time with different topics and exercises, but generally we spend around 90 minutes with one parent. And we asked them to bring someone who helped them make decisions about their baby during their pregnancy. So that meant that we had their mums, their sisters, their husbands, their wives and friends as well, taking part and discussing the Generation Study with us. During that time with them, we would test our materials. We listened out to what's important to them and what they asked about, and we got them to show us what would work better for them so that we could then shape the materials around that. Naimah: So you can find out a bit more about why it's important to involve users in co-design in our podcast ‘How has design research helped shape the Generation Study?’, which is available on our website. So, we have a list of frequently asked questions from some of the parents, and I wanted to post some of them to you today, Mathilde. So first of all, one of the questions was, why should my baby take part in this study? Mathilde: Yeah, I mean, that's really the key questions that all parents are asking themselves before they even spend any time finding out more about the Generation Study. And our materials do reflect that. So what tends to matter most to the parents we spoke to, is that there's a small chance that their baby may benefit directly from taking part because if a condition is suspected, they'll be invited for further specialised tests within the NHS, and they could receive treatment much sooner than if we had waited for the symptoms to develop and for a diagnosis to come, which can sometimes take years for some rare conditions. But for a large majority of the babies, 99%, they will have no condition suspected and so their involvement really is more altruistic. Taking part means that their parents agree to share the baby's healthcare records on an ongoing basis and their genome with researchers who can then look at this together with information from thousands of other babies and patients to help improve our understanding of genes and health. So taking part in the Generation Study also means that you might help uncover some life-changing early treatments for babies in the future. And finally, something that's super important to us is that people from Black, Asian and other minority et

In this explainer episode, we’ve asked Callum Morris, Pharmaceutical Research and Development Insights Manager at Genomics England, to explain what happens in a clinical trial. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Florence: What happens in a clinical trial? I'm joined with Callum Morris, Pharmaceutical Research and Development Insights Manager for Genomics England, to find out more. So, Callum, first things first. What is a clinical trial? Callum: So, a clinical trial is a study that looks to people to answer a specific medical research question. So, this involves gathering a group of participants that are willing to participate in providing evidence on how to improve clinical care. And so, the main purpose for a clinical trial is to evaluate health related outcomes between different groups of participants. If it's an interventional clinical trial, you change clinical care for one group and not another. And evaluate whether the change you made improved health outcomes for that group, or if it's an observational clinical trial, you might focus on different groups but not change anything about their clinical care and collect real world data to understand how outcomes differ across the groups. Florence: Can you briefly explain what we mean by real world data? Callum: Sure. So real world data relates to data collected routinely as part of standard clinical care. So, it could be collected from your electronic health records, data from product or disease registries, or data gathered from other sources such as digital health technologies. And all of this can inform on particular groups from the population you're interested in. Florence: And are there different types of clinical trials? Callum: Yes. Clinical trials can take many forms depending on the medical research question you're trying to answer. They could be related to understanding the risk of disease. So, evaluating a potential risk factor that you may be concerned with. They might evaluate preventing disease. So, what different approaches can you take to people who have never had the disease, and does this prevent its occurrence? You can have a clinical trial that looks at screening for disease. For cancer, that's really important. Does a new screening approach mean more people with cancer can be identified earlier? And importantly, does this lead to an improvement in survival? You can have clinical trials that evaluate the different approaches to diagnosing a disease and can you diagnose a patient earlier and better? And then the classical clinical trial is revolving therapeutics or different treatments, and you can have treatments that are addressing the disease itself. Or you'd have treatments that are controlling the symptoms of side effects you might get from another treatment you might be taking. So even within a specific medical research question, you can have different clinical trials depending on how much evidence you already have regarding that question. For clinical trials involving the assessment of new treatments and therapies, these are broken down into three stages and we call these phases. So, you have phase one, phase 2, and phase 3. Florence: Can you explain a bit more about these phases? Callum: Sure. So, the overarching medical research question might be, what is the safety profile of this new therapy, and does it work improving on the current standard of care? So, you'll break this down depending on the phase, and with each phase you expand your clinical trial to a larger population. Phase ones are typically on a small group of people around, let's say 20 to 50, and are designed to check the safety of a new drug that's being entered into humans for the first time. Sometimes, especially in early phase cancer trials, you're trying to find the right dose for your patients. So, you might take a small group, test them on a low dose, and if there are no severe reactions to the new drug, you start incrementally increasing your dose a little bit more. And this gives you a really good idea of the safety profile of your drug as you try it for the first time in a human population. Next, you'll move on to a phase 2. And these are typically larger than your phase one, around 50 to 200 people. And, usually you use the dose recommended by the phase one. So instead of slowly adjusting your dose and just focusing on the drug safety profile, the phase 2 will evaluate the safety of the medicine in a large population, but also have an additional focus on health-related outcomes. Is the medicine causing the effect you want? Whether that's relief of symptoms or for cancer reduction in the size of your cancer. If the data is really promising from your phase two, it will move t

In this explainer episode, we’ve asked Nicole Chai, Research and Development Bioinformatician at Genomics England, to explain what X-linked inheritance is. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Florence: How does X-linked inheritance work? I'm joined by Nicole Chai, Research and Development Bioinformatician for Genomics England, to find out more. So firstly, Nicole, can you explain a bit about the X and Y chromosomes? Nicole: Sure. So, the X and Y chromosomes are what we call sex chromosomes. And chromosomes are packages of DNA in our cells that are inherited from our parents, and they contain information about our physical and biological traits. Some examples of traits that are determined by our chromosomes include what colour our hair is and what colour our eyes are. And each of these individual traits are determined by smaller sections on the chromosome called genes. Genes can also determine what medical conditions we may inherit from our parents. As humans, we all typically have 23 pairs of chromosomes in each of our cells. One of these pairs consists of the sex chromosomes, and as their name suggests, sex chromosomes determine sex of an individual. And typically, females will have two X chromosomes and males will have one X and one Y chromosome. Florence: So then, what do we mean by the term X-linked condition? Nicole: So, an X-linked condition means that the condition is associated with genetic changes on the X chromosome. And what we mean when we say genetic changes are changes to the normal sequence of DNA on the gene. And this can sometimes lead to medical disorders. Florence: Do you have a specific example of an X-linked condition? Nicole: Sure. So, an example of an X-linked condition is Duchenne muscular dystrophy. And with this condition you get a progressive loss of muscle due to the lack of a protein known as dystrophin. Another example of an X-linked condition is red-green colour blindness. And this is where people affected with the condition can't see shades of red and green the way most people see them. Florence: Could you explain how X-linked conditions are inherited? Nicole: Sure. So, for many conditions, there are two ways they can be inherited, either dominantly or recessively. Dominant inheritance is usually when you just need one copy of the gene to be affected by the condition, whereas recessive inheritance is when you need two copies of the gene to be affected by the condition. However, this works slightly differently with X-linked conditions, and most X-linked conditions are inherited recessively. Florence: So why does inheritance work differently for X-linked conditions? Nicole: So the reason that inheritance works differently for X-linked conditions is down to the differences between sex chromosomes, between females and males. As females have two X chromosomes and males have X and Y, this means that for recessive excellent conditions, males only need one altered gene to have the condition. So, because males only have one X chromosome, if they inherit a faulty copy of a recessive gene, they don't have another healthy copy to compensate. On the other hand, as females have two X chromosomes, if they inherit just one faulty copy, they do have a healthy one that can compensate for that one. So as a result, what we tend to see is that males are more commonly affected by X-linked recessive conditions. Florence: That was Nicole Chai explaining the term X-linked inheritance. If you'd like to hear more explainer episodes like this, you can find them on our website www.genomicsengland.co.uk. Thank you for listening.

In this explainer episode, we’ve asked Arina Puzriakova, Scientific Curator at Genomics England, to explain what a polygenic disorder is. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Florence: What is a polygenic disorder? I'm joined by Arina Puzriakova, Scientific Curator for Genomics England to find out more. So, Arina, first things first. How can our genes affect our health? Arina: So, genes are short sections of DNA that contain information that the cells in your body need in order to make proteins. Each gene carries the instructions for making a specific protein, and each protein performs a different task that allows the body to develop and function properly, depending on the genes that we inherit from our parents. Also determines our unique physical features such as our eye colour, hair colour, and height. When a gene contains a change that disrupts the gene's instructions, also known as a gene variant, in some cases, this can lead to the production of a defective protein or prevents a protein from being made altogether. A missing protein or one that is not working properly can have a knock-on effect on how the body functions and this can result in health issues or the development of a genetic disorder. Florence: So then how can a gene variant lead to a disorder? Arina: So the genetics of each disorder are unique. In some cases, a change in a single gene is enough to cause a genetic disorder, and these are known as monogenic disorders. These conditions often occur in childhood and tend to cause severe illness. individually, they are more rare affecting a smaller number of people in the population, and usually they run in families as parents pass the damaging variance onto their children. But these changes can also happen spontaneously without a known cause. An example of a monogenic disorder, which some may be familiar with, is cystic fibrosis. Cystic fibrosis affects one in every 2,500 babies born in the UK, meaning that there's about 11,000 people living with cystic fibrosis. Florence: So, we've just talked through monogenic disorders. What do we mean by polygenic disorder? Arina: So polygenic disorders are on the other end of the spectrum for disorders. They are caused by the combined effects of multiple different genes. Individually, each gene has a very small effect on causing the disease, but many variations in different genes can act together to have a great impact on individual's susceptibility to that condition. Environmental and behavioural factors such as your lifestyle and diet also often have an effect. Polygenic disorders are much more common, typically affecting millions of people in the population, and they're usually diagnosed in adulthood. Florence: Could you give me an example of a polygenic disorder? Arina: A common example of a polygenic disorder is type two diabetes. It affects almost 4 million people in the UK. So this means that we know there are many genetic variants that could have made these individuals more susceptible to diabetes, but there are also other factors such as age or being overweight that could have increased their risk. Florence: Are there specific challenges when it comes to diagnosing or treating polygenic disorders? Arina: So, if I start with monogenic disorders, these are much easier to test for because we simply need to look for the presence or the absence of a faulty gene in order to determine whether someone is a carrier of a genetic disorder. On the other hand, testing for a polygenic disorder is a lot more complex as they are influenced by the combined effects of many genes. Meaning there is no single genetic test or treatment that will work for all patients with the same condition. We need large and diverse groups of patients to study in order to accurately determine which genes are important and which ones are not. And this can be challenging to obtain. Also accurately measuring and comparing lifetime environmental factors and exposures further complicates the assessment. Another challenge with polygenic disorders is that even though they can cluster in families, the inheritance is not as clear cut or predictable as it is with monogenic disorders. Carrying a specific combination of genetic variants that are already known to be associated with polygenic disorder does not necessarily mean that you will definitely develop that disorder. However, this information can be used to calculate something known as a polygenic risk score, and this provides an estimate for the risk of developing polygenic disease at some point in life based on individual's unique genetic profile. Florence: And why can knowing apologetic risk score be helpful? Arina: So, by being informed about the probabilit

The Generation Study is a research initiative aiming to explore the use of whole genome sequencing in newborns, to screen for more than 200 rare genetic conditions. This study will recruit 100,000 babies across England, and you can learn more about the Generation Study via the study's official website. Design research has played a vital role in shaping the Generation Study. Parents, NHS staff, and the public have been involved from the start, providing input through public dialogues and usability testing to guide the development of the study. In this episode, our guests discuss the use of design research in the Generation Study, and the importance of designing a robust and inclusive consent process, focusing on building trust and engaging diverse communities. They also discuss how the design of study materials such as posters, videos, and written content was shaped by community feedback. Our host, Öznur Özkurt, Director of design and research at Genomics England is joined by Mathilde Leblond, Senior Design Researcher at Genomics England, Rebecca Middleton, a rare condition patient, and Chair of the recruitment working group of the Generation Study and Sandra Igwe, CEO/founder of The Motherhood Group. "It’s not enough to just ask people afterwards. It’s also not enough to engage just at the beginning and then stop listening once we’re live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn’t considered before we launched, and just continue to learn." You can hear more information about Generation Study in our previous podcast episodes too: Genomics 101 with David Bick - What is the Generation Study? Which conditions will we look for initially in the Generation Study? With Vivienne Parry and David Bick You can download the transcript or read it below. Öznur: Welcome to Behind the Genes. Sandra: Every community’s different and every patient is different as well, and so that may require different focuses or different formats, or different messages for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so it’s really important to have representation because the lack of it in research can overlook communities’ specific concerns and needs. Öznur: My name’s Öznur Özkurt and I’m the director of design and research at Genomics England. On today’s episode, I’m joined by Mathilde Leblonde, senior design researcher at Genomics England, Rebecca Middleton, and Sandra Igwe, CEO and founder of the Motherhood Group. Today we’ll be discussing how design research was used in the Generation Study by involving participant and users’ voices to address ethical considerations, implementation and consent. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. So, before we dive into our questions, would our guests like to briefly introduce yourselves to our listeners? Sandra, let’s start with you. Sandra: Hi everyone, I’m Sandra Igwe and I’m the founder and chief exec at the Motherhood Group. The Motherhood Group is a social enterprise that supports black mothers, birthing people in their pregnancy and beyond. Öznur: Great to have you on the podcast, Sandra. Rebecca? Rebecca: Hi everyone, I’m Rebecca, I’m a rare condition patient, and I also have the pleasure of chairing the recruitment working group of the Generation Study. Öznur: Fantastic, thank you, Rebecca. And over to you, Mathilde. Mathilde: Hi, I’m Mathilde. I’m leading design research on the Generation Study, and I have had the pleasure of working with Sandra and Rebecca and many others, trying to shape the processes and materials of recruitment and consent in the Generation Study. Öznur: Fantastic, thank you. Mathilde, let’s start with our first question. What is the Generation Study? Mathilde: Sure. So, whole genome sequencing is a technology that’s improving. We’re finding new ways of using that, and there’s interest globally to explore the use of this technology to screen for rare genetic conditions in babies, so that we can treat them earlier on, so they’re not having two different departments trying to figure out what’s wrong with them. And because we can look for hundreds of conditions with whole genome sequencing, it’s really much more efficient, and we’re able to look at these rare conditions, so it’s really exciting. There’s still a lot of questions about implementing this operationally within the NHS, and so the Generation Study is aiming to explore this. We’re going to be aiming to recruit 100,000 babies across England to take part in this, and they will be staying on the Generation Study for 16 years, or until they withdraw, so that we can see how their health develops, and really understand how genes affect their health. Öznur: Thanks Math

In this explainer episode, we’ve asked Amanda Pichini, Clinical Director at Genomics England and Genetic Counsellor, to explain which healthcare professionals you may come into contact with in your genomic healthcare journey. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Florence: Which healthcare professionals are involved in my genomic healthcare journey? I'm joined with Amanda Pichini, Clinical Director for Genomics England, and genetic counsellor to find out more. So firstly, when someone has a genetic or genomic test, what kind of healthcare professionals might they come into contact with? Amanda: Well, everyone has a different journey, and it can depend on the type of test you have and the reason for having it. Some tests might only look for a single gene. Some might look at many genes, and some look for a very specific gene change that's already known to be in someone's family. Some genomic tests are there to find the cause of a person's diagnosis, understand more about their cancer, or maybe to predict a future health problem that they may have or that's in their family. So usually people start with their GP, who they go to with a question about their health or their child's health, and this could lead to them being referred to a clinical genetic service or perhaps another specialist team. Florence: So, then what is the purpose of a clinical genetics team? Amanda: Well, a clinical genetics team, in brief, aims to provide people that have a genetic condition or are at risk of one with health information, including information about prevention, counselling support, and genomic testing, and they focus on the whole family. Adults and children can both be seen in a genetic service. Clinical genetics teams tend to focus on rare conditions and rare predispositions to certain types of cancers, so really anything that might have a strong genetic basis and could impact someone at any stage of their life. A clinical genetics team is made up of a range of roles, and that could include clinical genetics, doctors, genetic counsellors, clinical scientists, and administrative staff. Florence: Could you tell me a little bit more about each of those roles? Amanda: Sure. I am a genetic counsellor, so I'll start with that. Genetic counsellors are specially trained healthcare professionals that help patients and families understand information about their genomic health, as well as provide guidance and emotional support. So, this could be about understanding their family history, making informed choices about having a genetic or genomic test, or helping them to come to terms with a result or a new diagnosis and the impact that could have on them or their family. Clinical geneticists are medically trained doctors that specialise in genetic conditions. They understand the underlying ways that genetics can affect health, and they use that to help make diagnoses for patients. How about genomic scientists? These are often not seen directly by patients, but they're vital to someone's genomic healthcare journey. So clinical genomic scientists and genetic technologists work in labs, and they're involved in processing patient samples, working with those other healthcare professionals to select the most appropriate genomic tests to perform and interpreting those results based on the variance or genetic changes that are seen in patients, which are usually summarised in a lab report. There's lots of other healthcare professionals that can also, um, be in a clinical genetics team. That could include administrative staff, family history coordinators, genomic practitioners or genomic associates. They might help arrange appointments, gather medical and family history details after a referral to help the clinical team know what might be done next. Some genetic services also have psychologists, nurses, or other allied health professionals embedded in their team or in specialty clinics that they work with, and it's really important that everyone is working together as a multidisciplinary team to help those patients and families in their healthcare journey. Florence: So, we know there are lots of different healthcare professionals within the clinical genetics team. Are there any other professionals involved in genomic healthcare as well? Amanda: Absolutely. As genomics becomes part of routine healthcare, that means there's lots of other healthcare professionals involved in arranging genomic tests and giving back results, or at least having initial discussions about genomic tests before referring on to another specialist. So, some examples might be midwives, arranging screening tests for women in pregnancy, a number of those screening tests have a genetic or genomic ba

Digital consent models, language barriers, and cultural differences are just a few factors that can exclude people from participating in genomic research. In this episode, our guests discuss these issues, and explore alternative methods such as in-person discussions and the use of trusted community figures to engage with their communities to increase awareness of genomic research. They also highlight the importance of communicating consent in ways that respect cultural dynamics, such as family involvement in decision-making. Our host, Naimah Callachand is joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager at Southall Community Alliance and Trupti Patel, Policy Manager at Genomics England. "I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community" You can download the transcript or read it below. Niharika: People are usually comfortable giving their data when they feel that there is transparency from the data collector, they’re being completely transparent, they come with you with clear benefits, how it’s going to benefit the community. And you are equally sort of agent of your own data and you feel involved in the research and you feel that you have power to give out your data and have control over the journey of that research. Naimah: My name is Naimah Callachand, and I’m the Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager for Southall Community Alliance, and Trupti Patel, Policy Manager at Genomics England. Today, we’re going to be discussing some of the ethical, legal and social implications of genomics research for diverse communities, and how we might overcome them to address the challenge of diverse communities health needs. If you enjoy today’s episode, we’d love your support, please like, share and rate us on wherever you listen to your podcasts. First of all, I’m going to ask each of our guests to briefly introduce themselves. Maili: I’m Maili Raven-Adams, I lead on work at the Nuffield Council on Bioethics to do with genomics. This has predominantly been looking at how to develop a best practice approach for genomics, and looking at the ethical implications of AI and genomics when they’re used together in healthcare. Before here, I worked at the Global Alliance for Genomics and Health, where I developed policies related to diversity in datasets and genomic discrimination, so I have a particular interest in this area. Naimah: Niharika, can we come to you? Niharika: Hello, everyone, I’m Niharika Batra, I’m the Community Projects Manager at Southall Community Alliance. We are a charity based in Southall. Prior to joining the charity, I was working as a Youth Community Engagement Assistant in United Nations Development Programme in India, and I have a background in gender and development. I also bring with me lived experience of being a South Asian immigrant woman, and I’m really passionate about working with the immigrant communities in the UK. Naimah: It’s lovely to have you. And Trupti, can we come to you? Trupti: Hi, I’m Trupti Patel, I’m a Policy Manager at Genomics England. I work primarily within the diverse data initiative and I lead the equity in health research workstream. My background is in responsible research and innovation, as well as co-production, and more ethical ways in which members of the public can shape the direction of scientific advancements. Naimah: So, first of all, Trupti, can we talk about the challenges around equity in data, and what this means for diverse groups in the context of genomics? Trupti: Yes, as I mentioned, I lead the equity in health research workstream. Now we talk very specifically about equity in health data. As Genomics England, we are a biobank, and we hold health data on individuals who have consented to be a part of genomic research. When we talk about equity, primarily we’re talking about those of non-European ancestry, and there are very specific reasons as to why that is. So firstly, there’s a wider issue about representativeness within health datasets more widely. We know that across all health data sets that are located within Global North countries, the data held within them tends to not be representative of their populations. And what I mean by that is that they tend to overrepresent those of European ancestry, and underrepresent anyone who is not of European ancestry. The consequences of this is that healthcare innovation might stand to leave these population groups behind. One of the other reasons that we talk about equity specifically, as opposed to things like equality, is that we’re also aware that if we look at research on a global level, the majority of research funding is given out thr

For Sickle Cell Awareness Month, our sickle cell Patient Voice Group discuss their lived experiences with sickle cell, shedding light on how organisations need to be considerate when engaging with patients. They emphasise the need for genuine engagement and transparency from researchers, while highlighting the importance of building trust within communities that have historically been overlooked. The discussion looks to the future, advocating for more personalised support, better treatment options and a stronger focus on the diverse experiences of those affected by sickle cell. Marie Nugent, Community Manager for the Genomics England Diverse Data Initiative co-hosts this episode with Natasha Gordon-Douglas, sickle cell patient advocate for the Genomics England Diverse Data Initiative and Lead Mentor at the Sickle Cell Society. They are joined by Oleander Agbetu, who cares for her son with sickle cell, and is also a member of the Solace sickle cell and thalassaemia support group board, and Jayson Kupoluyi, sickle cell advocate and volunteer for the Sickle Cell Society. The episode also features insights from some of the other members of the Patient Voice Group; Hazel Attua, Samuel Chuku and Zainab Garba-Sani. The Patient Voice Group are a group of people affected by sickle cell who share with Genomics England their expertise, based on their lived experience, to inform our sickle cell programme within the Diverse Data Initiative. "If we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone’s care, that’s what I want to do. That’s why I’m here." You can download the transcript or read it below. Marie: Welcome to Behind the Genes. Natasha: I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient’s voice in order to make things better, and not just be in a room where you’ve got all board members that think, “Okay, this is what is good for the patient.” No, actually, they’ve got the patients there to help support that voice, and saying, “Well actually, this is the reality,” rather than what you think might be the reality. Marie: My name is Marie Nugent and I’m the community manager for diverse data at Genomics England. I’ll be co-hosting today’s special patient takeover episode of Behind the Genes with Natasha Gordon-Douglas, who is a member of our sickle cell patient voice group. On this episode, we’re going to be speaking to two people who are also part of our patient voice group, Oleander Agbetu and Jayson Kupoluyi. Today we’ll be discussing what it’s like to live with sickle cell, and how organisations who wish to engage with patients need to be considerate of what is going on in people’s lives, and what good advocacy and support for patients who want to be involved in research looks like. If you enjoy today’s episode, we would love your support. Please like and share, and rate us on wherever you listen to your podcasts. Welcome everyone, thank you very much for your time today to talk about the patient involvement and engagement work we’ve been doing as part of our sickle cell and genomics programme at Genomics England. My name’s Marie, I’m the community manager for the diverse data initiative, and I am really involved in doing the sickle cell engagement work. I’m going to pass straight to Natasha now, who’s going to be my lovely co-host for this podcast. So, over to you, Natasha. Natasha: Thank you, Marie. I’m Natasha. I would say my background is nothing to do with the medical side. My background is in marketing and the corporate world. That’s how actually I got introduced by John James, because I actually got him into our workplace to do a podcast about sickle cell. So, you know, just – I’m working in an environment, which obviously – it’s about people understanding about my illness, so I actually got him in speaking, and then he mentioned about a project, “Oh, you might be interested in this.” So, that was kind of the introduction I got from John James. But as I said, doing patient work and engagement stuff was completely new to me, so this is my – I’m a rookie, I should say. But I feel like now after the two years, I know now, I understand [laughter]. But yeah, that’s kind of a quick background. And how I got introduced to Marie is from John James at the Sickle Cell Society. Marie: Great, thank you, Natasha. So, coming straight to you now, Oleander, I think it’s a bit different for you. So, you joined this particular group not too long ago, but from what I know, you’ve been doing this kind of advocacy work and engagement work for quite a while. So, tell us a bit about yourself. Oleander: Well, I’m a parent/carer of a teenager, young man with sickle cell, and I think I’ve been part of the Solace sickle cell and thalassaemia support group board for more than ten years now. And what we do is we support patients through our WhatsApp group, as well as through inviting different people to come a

In this episode of Behind the Genes, we explore the challenges diverse communities face in accessing genomic medicine. The discussion focuses on issues including language barriers, cultural differences, and socioeconomic disparities that hinder marginalised communities from accessing and benefitting from genomic medicine. Our guests delve into successful strategies for engaging these communities in healthcare research and decision-making, highlighting the importance of building trust with groups that have historically been underserved or mistreated. The episode also emphasises the need for culturally sensitive communication from healthcare professionals and how meaningful community engagement can foster collaboration and trust within genomic research. Our host, Naimah Callachand is joined by Aman Ali, a Community Ambassador at Genomics England and Community Engagement Manager at Our Future Health, Anna Smith, Child and Adolescent Integrative Psychotherapist at Rareminds, and Moestak Hussein who works for Bristol City Council in Public Health & Communities, working directly to build and imbed cohesion, inclusion and social justice approaches in her role. "If we talk about co-production, true co-production is really creating a power balance where there’s no hierarchy. It’s an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve." You can download the transcript or read it below. Naimah: Welcome to Behind the Genes. Aman: It’s really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with. Naimah: My name is Naimah Callachand and I’m Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m going to be joined by Anna Smith, child and adolescent integrative psychotherapist for Rare Minds, Aman Ali, a community ambassador for Genomics England, and Moestak Hussein, community coordinator at Bristol City Council. Today, we’ll be discussing the disparities in access to genomic medicine amongst diverse communities. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. Aman: Hi, my name’s Aman Ali, I am an ambassador at Genomics England, a person very passionate about health research and ensuring that diverse communities are involved in health research, and I work as a community engagement manager at Our Future Health. Anna: My name’s Anna Smith, I’m a psychotherapist. I work in private practice and also with Rare Minds, who are a company who provide therapy to people with rare and genetic conditions. Moestak: Hi, my name is Moestak Hussein and I have a background in community development, and I’m passionate about tackling health inequalities, and building social justice and inclusive approaches to address health inequalities. I work at Bristol City Council in the public health team, and I’ve participated in the Bristol workshops around equity in research in genomics. Naimah: So, let’s jump in and first of all I want to talk about barriers to access for diverse communities. I want to talk about how there are language barriers, cultural differences and socioeconomic factors that impact access to genomic medicine for marginalised communities. Anna, I wonder if you maybe could talk to me a bit about this. Anna: Yeah. So, I’m talking about the traveller community, and we refer to this community as a GRT community, which is Gypsy, Romany and Traveller, so it encompasses people in the UK, people living in Ireland as well. And some of the barriers to accessing healthcare are a lack of understanding of culture. There’s been studies done where it says that people from GRT communities show up lower on all markers for poor healthcare and poor mental healthcare, and part of the reason for that is things like illiteracy. You know, you’re dealing with people who can’t read or write. They can’t read appointment times. They don’t have access to public transport. A lot of women don’t drive in this community, and also women are not very well supported within the community by the people who can drive and who can get them places, because it’s not seen as something that they need access to. Because the community is so closed, everything sort of takes place within the community. In terms of genomic healthcare, access right from the start of life, if people are not accessing healthcare right from birth, they’re not getting the genetic testing that’s needed, so then a lot of these things don’t even show up until the illness presents itself, and then accessing healthcare from there is really d

Pharmacogenomics plays a critical role in personalised medicine, as some adverse drug reactions are genetically determined. Adverse drugs reactions (ADRs) account for 6.5% of hospital admissions in the UK, and the application of pharmacogenomics to look at an individuals response to drugs can significantly enhance patient outcomes and safety. In this episode, our guests discuss how genomic testing can identify patients who will respond to medications and those who may have adverse reactions. We hear more about Genomics England's collaboration with the Medicines and Healthcare products Regulatory Agency in the Yellow Card Biobank and our guests discuss the challenges of implementing pharmacogenomics into the healthcare system. Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Anita Hanson, Research Matron and the Lead Research Nurse for clinical pharmacology at Liverpool University Hospitals NHS Foundation Trust, and Professor Bill Newman, Professor of translational genomic medicine at the Manchester Center for Genomic Medicine, and Professor Matt Brown, Chief Scientific Officer at Genomics England. "I think we’re moving to a place where, rather than just doing that one test that might be relevant to one drug, we’d be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it’s required, so that they’re not waiting for the results of a genetic test, it’s immediately within their healthcare record." You can watch this video learn more about Jane's lived experience with Stevens-Johnson syndrome, on The Academy of Medical Sciences' (AMS) YouTube channel. The story, co-produced by Areeba Hanif from AMS, provides an in-depth look at Jane's journey. Want to learn more about personalised medicine? Listen to our Genomics 101 episode where Professor Matt Brown explains what it is in less than 5 minutes: Genomics 101: What is personalised medicine? You can download the transcript or read it below. Vivienne: Hello and welcome to Behind the Genes. Bill: What we’ve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They’ve been easier to identify and there’s a clear relationship between some drugs and some genetic changes where that information is useful. So, a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you’re given that treatment, then you can end up on intensive care and die, so it’s a really significant side effect. But as you say, the most common side effects aren’t necessarily fatal, but they can have a huge impact upon people and on their wellbeing. Vivienne: My name’s Vivienne Parry and I’m head of public engagement at Genomics England, and today we’ll be discussing the critical role of pharmacogenomics in personalised medicine, highlighting its impact on how well medicines work, their safety, and on patient care. I’m joined today by Professor Bill Newman, professor of translational genomic medicine at the Manchester Centre for Genomic Medicine, Anita Hanson, research matron, a fabulous title, and lead research nurse for clinical pharmacology at the Liverpool University Hospital’s NHS Foundation Trust, and Professor Matt Brown, chief scientific officer for Genomics England. And just remember, if you enjoy today’s episode, we’d love your support, so please like, share and rate us on wherever you listen to your podcasts. So, first question to you, Bill, what is pharmacogenomics? Bill: Thanks Viv. I think there are lots of different definitions, but how I think of pharmacogenetics is by using genetic information to inform how we prescribe drugs, so that they can be safer and more effective. And we’re talking about genetic changes that are passed down through families, so these are changes that are found in lots of individuals. We all carry changes in our genes that are important in how we transform and metabolise medicines, and how our bodies respond to them. Vivienne: Now, you said pharmacogenetics. Is it one of those medicine things like tomato, tomato, or is there a real difference between pharmacogenetics and pharmacogenomics? Bill: So, people, as you can imagine, do get quite irate about this sort of thing, and there are lots of people that would contest that there is a really big important difference. I suppose that pharmacogenetics is more when you’re looking at single changes in a relatively small number o

In this episode, we delve into the impact of the new groundbreaking research uncovering the RNU4-2 genetic variant linked to neurodevelopmental conditions. The discovery, made possible through whole genome sequencing, highlights a genetic change in the RNU4-2 gene that affects about 1 in 200 undiagnosed children with neurodevelopmental conditions, making it more prevalent than previously thought. This discovery represents one of the most common single-gene genetic causes of such conditions. Our host, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Lindsay Pearse who shares her journey through the diagnosis of her son Lars. They are also joined by Sarah Wynn, CEO of Unique, and Emma Baple, Clinical Genetics Doctor and Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub. We also hear from the 2 research groups who independently discovered the findings: Dr Andrew Mumford, Professor of Haematology at the University of Bristol Link to the research paper: Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders Assistant Professor Nicky Whiffin, Big Data Institute and Centre for Human Genetics at the University of Oxford Link to the research paper: De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome To access resources mentioned in this podcast: Unique provides support, information and networking to families affected by rare chromosome and gene disorders - for more information and support visit Unique's website. Connect with other parents of children carrying a variation in RNU4-2 on the RNU4-2 Facebook group. "I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future." You can download the transcript or read it below. Naimah: Welcome to Behind the Genes. Lindsay: So, this feeling that like we’ve been on this deserted island for eight years and now all of a sudden, you’re sort of looking around through the branches of the trees. It’s like, wait a minute, there are other people on this island and in this case actually there's a lot more people on this island. Yeah, it’s very exciting, it’s validating. It gives us a lot of hope and, you know, it has been quite emotional too and also a bit of an identity shift. Being undiagnosed had become quite a big part of our identity, and so now that’s kind of shifting a little bit that we have this new diagnosis and are part of a new community. Naimah: My name is Naimah Callachand and I’m Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m joined by Lindsay Pearse whose son Lars recently received a genetic diagnosis, made possible by research using data from the National Genomic Research Library, Sarah Wynn CEO of Unique, and Emma Baple, a clinical genetics doctor. Today we’ll be discussing the impact of recent research findings which have found a genetic change in the non-coding RNU4-2 gene, to be linked to neurodevelopmental conditions. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. Naimah: And first of all, I would like everyone to introduce themselves. So, Lindsay, maybe if we could come to you first. Lindsay: Great, thank you. So, thank you for having me. I’m Lindsay Pearse, I live outside of Washington DC and I’m a mum to 3 boys. My oldest son Lars who is 8, he was recently diagnosed with the de novo variant in the RNU4-2 gene. Naimah: Thank you. And Emma? Emma: My name is Emma Baple. I’m a Clinical Genetics Doctor which means I look after children and adults with genetic conditions. I’m also a Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub. Naimah: And Sarah? Sarah: Hi, thank you for having me. I’m Sarah Wynn, I’m the CEO of a patient organisation called Unique, and we provide support and information to all those affected by rare genetic conditions. Naimah: Great, thank you. It’s so great to have you all here today. So, first of all Lindsay, I wonder if we could come to you. So, you mentioned in your introduction your son Lars has recently been diagnosed with the de novo variant. I wondered if you could tell us a bit about your story, and what it’s been like up until the diagnosis. Lindsay: Sure, yeah. So, Lars is, he’s a wonderful 8 year-old boy. With his condition, his main symptoms he experiences global developmental delays, he’s non-verbal. He’s had hypertonia pretty much since birth and wears AFO’s to support his walking. He has a feeding disorder and is fed by a G-Tube. Cortical vision impairments, a history of seizures and slow growth,

Genomics has changed considerably over the past 10 years, and we are now exploring how to integrate it into routine healthcare. In this episode, our guests reflect on this evolution and discuss how the key learnings from the past 10 years can shape the genomics ecosystem of the future. They highlight the importance of partnership across teams, organisations and participants, emphasising the importance of keeping participant and patient benefit at the heart of research, whilst also addressing the ethical and safe storage of patient data. In this episode, our host, Helen White, who is the Participant Panel Vice-Chair for cancer at Genomics England, speaks with Dr Rich Scott, CEO of Genomics England. "There’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care." You can download the transcript or read it below. Helen: Welcome to Behind the Genes. Rich: There’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care. Helen: My name is Helen White and I am the Participant Panel Vice Chair for Cancer, at Genomics England. On today’s episode I’m joined by Dr Richard Scott, Chief Executive Officer for Genomics England. And today we’ll be discussing Richard’s recent appointment as CEO, lessons learnt from the last ten years in the evolution of genomics in healthcare, and how these learnings will be taken forward in the next ten years. And we’ll also visit the importance of keeping participant and patient benefit at the heart of research, as well as the ethical and safe storage of patient data. If you enjoy today’s episode we would love your support: please like, share and rate us on wherever you listen to your podcast. Before we dive into the interview with Rich, I wanted to take a moment to share my story and tell you a little bit about myself. I have been a member of the Participant Panel at Genomics England since 2018. It was the year before that when I was diagnosed with endometrial, or womb cancer, and was offered the chance to join the 100,000 Genomes Project, which felt like something positive at what was otherwise quite a scary time. It turns out that I have something called Lynch syndrome, that’s a genetic condition that increases my chance of developing certain cancers, particularly womb and bowel cancer, which is actually a really useful thing to know as there are things I can do to reduce my chance of getting cancer; things like having regular colonoscopies and taking daily aspirin. I have now been on the participant panel for six years and one year ago I was appointed as Vice Chair for cancer. This is a new and developing role and I am excited to have so far helped recruit more people with lived experience of cancer to the panel and to be assisting Genomics England with connecting to organisations that advocate for people whose lives have been touched by cancer. So that’s enough about me. I am delighted to be joined today by Richard Scott, and I am very much looking forward to our conversation. Welcome, Rich. Thank you. So Rich, you’ve recently been appointed CEO of Genomics England. Can you tell me a bit about your background and what brought you to this role? Rich: It’s a really good question and it’s one that doesn’t have a really very simple answer. I guess what it boils down to is I guess I’ve always had an interest, even as a child, for whatever reason, in genetics and genomics. I have also then always been drawn to things where I can have an impact and particularly the impact in healthcare and that’s what took me to being a medical student. And I guess it’s that combination of that particular interest in genetics and being able to see, even when I was at medical school I qualified in 2000 that this was an area of medicine that was going to be really important in the future. And then as I trained, as I did a PhD and as I saw the technology develop and change and then when I saw the UK government and the NHS investing in genomics in a really foresighted way, I found myself eight or nine years sitting at Great Ormond Street as a consultant in clinical genetics where I still practice, I still do one clinic a month there as a clinical genetics consultant seeing families with rare conditions. But I could see when Genomics England was established that this was something, as I said, really foresightful where we could really collectively across the country make more of a difference t

In this explainer episode, we’ve asked James Duboff, Strategic Partnerships Director at Genomics England, to explain how genomic data can be used in drug discovery. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Naimah: How do pharmaceutical companies use genomic data for drug discovery? Today, I’m joined by James Duboff, a Strategic Partnerships Director here at Genomics England, to find out more. So James, first of all, what is genomic data, and how does this relate to our genes? James: Let’s start with a simple explanation of what we mean by genomic data and our genes. So, every cell in our body contains a complete copy of our genome. Now, genome is kind of a mini instruction manual that describes exactly how to make you. Now, those instructions are written in a language called DNA, which is over 99 percent identical in every single human on the planet, so you and I are actually genomically very, very similar. The differences, however, are called variants, and they’re what make us unique. Now, some of those variants can actually be very dangerous, and they can code for things like rare genetic diseases or even cancer. So, we need to read in detail exactly what’s going on in your DNA and in your genome to see where changes are and where those variants really are, and we do this by sequencing the genome. So, if you get a DNA sequence, that’s effectively an electronic readout of your genomic data, which is your genome in computational form. Now, understanding that and working with that is still a relatively new field, so what we try and do is connect the genomic data, your genome, with health information, such as hospital records and what you’re presenting with in clinic, if you’re in a patient setting, and look at those together to give context to those variants in the genome. So, genomic research is actually where we look at how genes and physical outcomes could be linked. So thinking of, you know, biology and physiology term, what does a variant exactly do and how might it cause a disease. Naimah: You mentioned both the genome and whole genome sequencing, and if our listeners aren’t too sure exactly what they are, they can listen to some of our other explainer episodes with Greg Elgar, who explains these concepts. So James, next could you tell me why are pharma and biotech companies interested in genomic data? James: Ultimately, pharma and biotech companies are interested in genomic data because that really tells them what’s going on within the blueprint or that mini instruction manual of an individual. So, pharma and biotech have dedicated research teams that focus on genomic research, and they look through genetic databases across the world, such as Genomics England and others, to really understand the role of the genome in their target disease areas. By looking at those, that helps them develop new drugs and tools to specifically diagnose, treat and also even cure these diseases. Naimah: So, how exactly do they do that? Can you explain it in some simple steps? James: I think there are four key areas that they need to focus on. So, starting with the first, where, whereabouts on a genome should they focus? Now, the way that a pharma company would do this, or any researcher really, is by taking two populations of people. So, you’d take a population who have a known disease, and you’d compare that to people without. Now if you’re looking at the genomes of people with the disease and those without the disease, you can kind of play spot the difference between those two, and understand whereabouts on the genome variants appear for the disease population and not for the healthy or undiseased control group. Now, when you do that, you can kind of pinpoint exactly whereabouts you see variants only in that patient population. That helps you identify your target, and that’s known as target identification, which is essentially pinpointing that spot on the genome that’s linked only to the disease. Once you know that, you can use that as a potential target for a new drug. So, once you’ve found that variant, the next step was, what does that variant do? Is it potentially overproducing something? Is it activating a promoter and therefore making more and more and more of a gene product that, you know, might be toxic inside a person if you have too much? Even too much of a good thing could be a bad thing. So, is that the case? Or does that variant cause an underproduction or something to just be not actually made by your body at all? So, if that variant kind of interferes with a piece of genetic code, it could stop that gene from producing anything, and therefore you might be effectively detrimented and deprived of that particular gene product. And b

Ethical considerations are essential in genomic medicine and clinical practice. In this episode, our guests dive into the details of ethical principles, highlighting how they can be brought into practice in the clinic, whilst considering the experiences and feelings of patients and participants. Our host, Dr Natalie Banner, Director of Ethics at Genomics England, speaks to Professor Sir Jonathan Montgomery and Dr Latha Chandramouli. Jonathan is the Chair of the Genomics England Ethics Advisory Committee, and a Professor of Health Care Law at University College London. Latha is a member of the Ethics Advisory Committee and the Participant Panel at Genomics England, and is a Consultant Community Paediatrician working with children with complex needs. "You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don’t want to have separate discussions of things." You can download the transcript or read it below. Natalie: Welcome to Behind the Genes. Jonathan: The first difference is that the model we’ve traditionally had around clinical ethics, which sort of assumes all focus is around the patient individually, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions. Families differ enormously, some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approaches to genomic issues must respect everybody in that. Natalie: My name is Natalie Banner and I’m the Director of Ethics here at Genomics England. On today’s episode, I’m joined by Chair of our Ethics Advisory Committee, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli, member of the Ethics Advisory Committee and the Participant Panel, who’s also a community paediatrician working with children with complex needs. Today we’ll be discussing why ethical considerations are crucial in genomics research and clinical practice and what consent means in the context of genomics. If you enjoy today’s episode, we’d love your support. Please like, share and rate us wherever you listen to your podcasts. At Genomics England, we have an Ethics Advisory Committee, which exists to promote a strong ethical foundation for all of our programmes, our processes, and our partnerships. This can mean things like acting as a critical friend, an external group of experts to consult. It can mean ensuring Genomics England is being reflective and responsive to emerging ethical questions, especially those that arise as we work with this really complex technology of genomics that sits right at the intersection of clinical care and advancing research. And it can also ensure that we are bringing participant voices to the fore in all of the work that we’re doing. I’m really delighted today to welcome two of our esteemed members of the ethics advisory committee to the podcast. Professor Sir Jonathan Montgomery, our Chair, and Dr Latha Chandramouli, member of our Participant Panel. So, Jonathan, if I could start with you, could you tell us a little bit about your background and what you see as the role of the ethics advisory committee for us at Genomics England? Jonathan: Thanks very much, Natalie. My background professionally is I’m an academic, I’m a professor at University College London, and I profess healthcare law the subject that I’ve sort of had technical skills in. But I’ve also spent many years involved in the governance of the National Health Service, so I currently chair the board of the Oxford University Hospital’s NHS Foundation Trust. I’ve spent quite a lot of time on bodies trying to take sensible decisions on behalf of the public around difficult ethical issues. The most relevant one to Genomics England is I chaired the Human Genetics Commission for three years which was a really interesting group of people from many backgrounds. The commission itself primarily combined academics in ethics, law and in clinical areas, and there was a separate panel of citizens think grappling with things that are really important. Genomics England has a bit of that pattern, but it’s really important that the ethics advisory committee brings people together to do that. You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don’t want to have separate discussions of things. My aim as Chair of the advisory committee is essentially to try and reassure myself that we’ve heard all the things that we need to hear and we’ve had a chance to discuss with each other as equals what it is that that leads us to think, and then to think about how to advise within Genomics England or other people on

In this explainer episode, we’ve asked Professor Matt Brown, Chief Scientific Officer at Genomics England, to explain what personalised medicine is and how it could change the way we treat genetic conditions and cancer. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Naimah: What is personalised medicine? I’m joined by Matt Brown, chief scientific officer for Genomics England, to find out more. So, first of all, Matt, can you tell me, what is personalised medicine? Matt: So, personalised medicine is about giving the right dose of a medicine and the right medicine to the right person. So, it’s exactly the opposite of one size fits all. It’s what doctors have been trying to do ever since we had effective medicines, that is generally looking at the patient, what disease have they got, what factors are there about the patient that can help judge what dose they should give and for how long, of which medicine. Naimah: So, people often refer to this as precision medicine. Is this the same thing? Matt: Generally, the two terms are used interchangeably. I think precision medicine is more specifically about the dose perhaps, but effectively they both mean the right medicine at the right dose for the right person. Naimah: And how can we predict what treatment will suit each individual patient best? Matt: Well, to some extent, of course, this depends on the disease the patient actually has. We also know from a patient’s history how they’ve reacted to similar medications in the past. So for example, some patients have lots of problems with anti-inflammatories, other patients don’t, so if you give an anti-inflammatory to somebody who’s had problems with them before, you’re likely to cause the same problems all over again. So nowadays, we have much, much better ways, other than trial and error, to predict what treatment will suit a patient best, and in particular, development of genetic markers to look at how their condition is going to respond best, and how the patient is going to tolerate the medicine you give them, and what dose you should be giving them. Naimah: How could personalised medicine change the way we treat genetic conditions and cancer? Matt: So, I’ll talk about cancer first up. In the past, we used to treat cancers based on the organ from which the cancer actually arose, and the more we’ve learnt about what the genetic mutations are that cause cancers, the more cancer treatments are being decided based on the genetic mutation which is driving the cancer, and this has proven to be more effective than just looking at the organ from which the cancer arose. It turns out then that some medications which were only being used for specific cancers, are actually useful across multiple cancers that are driven by the same genetic mutations. In lots of other common diseases though, we now know a lot about genetic variants which predispose people to adverse drug reactions, and so we can use genetic tests to predict who’s going to get those adverse drug reactions and avoid them. And similarly, we also know about genetic determinants of how people metabolise and, in many cases, activate medications, and that helps us a lot learning about what dose to give people. Naimah: And how far away are we from seeing this routinely in clinical care? Matt: We are seeing it in routine clinical care in some pretty narrow settings. So, there are genetic tests available for enzymes which are involved in activation of particular chemotherapy 5 agents. So, DPYD testing, for example, is widely used to predict people’s likely response to a class of chemotherapy agent called fluoropyrimidines, or 5-Fluorouracil is a common one, and the genetic test basically picks out a group of people, a small number of people who are likely to have severe adverse drug reactions to that class of medication, and that’s been a really big success. We also use it for picking some other severe adverse drug reactions to medications like gout medications, HIV medications and so on, but generally it’s pretty narrow. What we want to get to the point is where we have people tested in advance of them needing medications, so that when they go to the doctor to be seen about a particular condition, the doctor already has the genetic test available to them, so the doctor can say if the medication is safe and what dose to use. This is what we call pre-emptive testing. Naimah: That was Matt Brown explaining what is personalised medicine. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.

In this explainer episode, we’ve asked Will Navaie, Head of Ethics Operations at Genomics England, to explain what ethics is and why it's important, in the context of genomics. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. Want to find out more? Check out the blog 'Genomics 101: What is ethics?'. You can download the transcript or read it below. Naimah: What is ethics? Today I’m joined by Will Navaie, who’s Head of Ethics Operations at Genomics England, to find out more. Will: Ethics is part of philosophy, and it’s part of philosophy that talks through a set of moral principles that govern our behaviour and our conduct. So, it might be thinking about whether something is good or bad. It might be thinking about whether something is good or better, or whether something is bad and worse. So, it’s about values and how we demonstrate those values kind of in a moral framework. So, I like to think of ethics as, just because you can do something, it doesn’t mean that you should do something. So, the law dictates to us what we can do, but ethics then talks about actually you need to look at the context around a law and to see whether something is reasonable, and so ethics to me is the should. So, should we do something? Just because we can do something, it doesn’t mean that we necessarily should do that thing. So, in medical ethics, we have four pillars or four areas that we concentrate on. One is justice, and that’s making sure that something is fair and equitable and inclusive. And equity being the key here, so equity recognises that individuals have different circumstances, and equity allocates opportunities based on the needs of the individual. So, it’s not about giving everybody the same, but it’s recognising that to get an equal outcome for something, that some people will require more of something because of their set of circumstances. We also have autonomy, and autonomy in medical ethics is a bit of a focus sometimes, and what that is, is giving choices and respecting people’s decisions around that choice. Consent, we talk about a lot in medical ethics, but it is not the be all and end all. It’s really important, but actually it’s one principle among many that kind of make up ethics. Another one of those four is beneficence, and that’s talking about everything we do must create benefit for people, and that benefit might be at an individual level, it might be at a societal level, so there’s lots of different ways of realising benefit. And the other, which is the flipside of that, is non-maleficence, and that’s making sure that everything we do doesn’t cause any harm to people. Naimah: Okay, and then so if we’re thinking about ethics in the context of genomics, what does that mean? Will: So, those four principles that we just talked about are applied to genomics as much as anything else, so there’s no exceptionalism to those, so we live by those four pillars, if you like. But what does make things complicated in genomics is that genomic data is not just about you. It’s not just about an individual. It’s about your family, it’s about your future family, and what that means is that we need to take those four pillars, those four areas, and look at them through a lens of a group rather than an individual. Where it becomes more complicated is the kind of interface between the law and ethics, and the way that the laws are written in this country and in healthcare are very much around individual rights, and that becomes really tricky when the decision making of an individual can affect other people in their family. And so, what we try to do is to think about how we can influence behaviour that we want to see. So, the law says an individual has to give their consent for a thing to happen. What we do is we take a step back and we say, “okay, but because there’s other people involved, we need to respect that.” And so, we’re constantly thinking about how can we influence the behaviour that we want to see. So, we might say, “when you are thinking about whether you want to take part in medical research, or genomic medical research, you might want to speak to your family about this. You might want to speak to your children about this, because it does have implications on them.” And so again we’re using the sort of vehicle of consent to try and nudge those behaviours that we want to see. So again, it’s this kind of ethics complementing the law. So, the law’s not really working – it’s working to protect an individual, but it’s not necessarily respecting everybody, and so we just try to kind of affect those behaviours as much as we can. Naimah: Okay, and then what’s the best way to demonstrate ethics? Will: I think that’s a really interesting question, and I think it’s really important because ethics bei

In this explainer episode, we’ve asked Marie Nugent, Community Manager for the Diverse Data Initiative at Genomics England, to explain what diversity is and why it's important, in the context of genomics. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Naimah: Why is diversity important in genomics? Today, I’m joined by Marie Nugent, who’s an engagement manager for the Diverse Data Initiative at Genomics England, and she’s going to explain more. So first of all, Marie, let’s start at the beginning. What is diversity? Marie: I think it’s sort of a fiendishly seeming simple question, isn’t it, what is diversity, and I think you’ll get just as broad a range of answers as the people you might ask that question to. But for me, you know, it’s really got to be about how we do things. So to me, diversity is about recognising that there’s maybe a limited way in which certain things work, or the way in which we might go about doing certain things, and it’s also limited in terms of who’s involved in that and who might benefit from that. So, in the broadest sense, I think diversity means recognising the limitations of maybe what you currently do, and really looking for how can we open that up a lot more to provide the space and opportunity for a broader range of people and voices and experiences to really be brought into that and shape it. Naimah: And can you tell me a bit more about what diversity means in the context of genomics? Marie: I find this absolutely fascinating in the context of genomics, because genomics is really about how do we understand, you know, how our DNA, as an entire piece of information, is building us and shaping us as people, and having an impact on our lives, and, you know, for us predominantly our health. And the way in which we currently think about grouping people in genomics is unfortunately still very, very heavily influenced by social understandings of how people group together, not necessarily anything that’s really about your genetic ancestry, for example, which is very different. So at the moment, you know, it’s an interesting thing to play with and think about because in genomics it’s absolutely crucial that we understand the broadest sense of human diversity in terms of genetics and genomics, and only by doing that can we start to really fully understand what it means to be distinct, and therefore how small changes in DNA can have a massive impact on people’s health. So, diversity in the context of genomics has to actually completely change the very fundamental ways in which we currently understand how people group together, so it’s really getting at the heart of that academic thinking about the topic. But it’s more than that, of course, as well, because as I’ve sort of already mentioned about what diversity means more broadly, it’s got to be about how we do things and who’s involved in that, and who benefits from it. So, in the context of genomics, it’s playing at the ideas of how we even understand how people relate to each other and how they’re different from each other, as well as how we do things. It’s a really complex but fascinating topic, to be honest, to be able to look at and study in some way. Naimah: How does the inclusion of diverse populations contribute to improving genomic research? Marie: Yeah, so following on from what I’ve just said, we fundamentally need to include everyone, you know. In order for us to really understand what genetic ancestry means and what difference looks like across different groups, and how that impacts health, we have to be able to capture, as best as we possibly can, you know, what true genetic diversity looks like in people. So, including as many people as possible who are different from what we currently understand is absolutely crucial. It’s the only way in which we can progress this area. And as I say, that’s in terms of how we think about it maybe academically and what we can do in terms of research, and what we understand, but it’s got to also be about the practice and how we do things. So, there’s involving people and having good representation of people in, say, data, but we have to think about how we’re involving people in how we do things and how we understand things, and how we make decisions about these things too. Naimah: So, for these large groups of people, what are the challenges and barriers for including everyone? Marie: So, I think there are a lot of challenges and barriers that hinder the inclusion of a broader range of groups of people in studies. I suppose the main one that I’m going to focus on is it’s actually the way in which we do research. It’s actually our culture, if you like, of work in this area. That’s one of the biggest barriers, and tha

In this explainer episode, we’ve asked Ellen Thomas, Interim Chief Medical Officer at Genomics England, to explain what genetic and genomic tests are, why someone might do a test, and how they are performed, in less than 10 minutes. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. You can download the transcript or read it below. Naimah: What is genetic or genomic testing? Today, I’m joined by Ellen Thomas, interim chief medical officer for Genomics England, who’s going to explain more. So, first of all Ellen, what is a genetic test? Ellen: Well, genetic tests examine a person’s genes to see if they have any changes in their DNA which might explain their symptoms. We all have DNA in most of the cells of our bodies, we inherit it from our parents and pass it on to our children. DNA provides the blueprint for our genes, and the proteins which build and run our bodies. Nearly all of our DNA is exactly the same across all of us, but around 5 million out of our 3 billion DNA letters are different, and each of these we call a genetic variant. The pattern of genetic variants that we all carry helps to make us who we are, and genetic testing is designed to examine some of these variants to help inform our healthcare. Naimah: So, why are they sometimes called genetic tests and sometimes called genomic tests? Ellen: Well, the words genetic and genomic are often used in exactly the same way, but broadly, genetic tests are usually used to look at just one or a small number of a patient’s genes, while a genomic test will look at hundreds or even thousands of genes at the same time. In general, it’s fine to use either. Naimah: If you want to hear more about the difference between genetics and genomics, you can find another explainer episode with Rich Scott on our website, which goes into more detail. Okay, so coming back to you, Ellen, what are the reasons we might do a genomic test? Ellen: Some rare health conditions are caused by DNA variants in our genes, conditions such as cystic fibrosis, Huntington’s disease or sickle cell disease. In these 3 conditions, there is usually just one gene that is responsible, the same gene for all patients. That means that you can often find the DNA variant which has caused a patient’s symptoms by doing a test which looks just at that gene, or even sometimes just at a part of the gene. But for other genetic conditions, a variant could be found in any of dozens or even hundreds of genes, which could cause the same condition or a group of conditions, and examples of that include familial forms of epilepsy or developmental disorders in children. For these conditions, to find an answer you often need to do a broader genomic test, looking at many genes at the same time, and also sometimes in between the genes. Finding the variant in a patient’s DNA which has caused the condition is useful, because it helps understand how the condition is passing down in the family, and whether it could affect anyone else in the family in the future. It is also increasingly used to work out which treatment an individual patient might respond to best. Genomic tests are also used to help diagnose and treat cancer. A tumour develops and spreads because new variants in the DNA build up inside the tumour, which are not present in the patient’s healthy cells. By testing the DNA of the tumour, you can sometimes understand more about why it happened and what treatment might be most effective. Naimah: So, can you tell me a bit about what sort of questions you can and can’t address with genomic testing, and how has this changed over time? Ellen: Well, at the most basic level, if a condition is not caused by DNA variants, then a genomic test will not provide any useful information. So, doctors use genomic tests when they suspect that a patient might have an explanation of their symptoms in their genes, but we don’t always find an answer. Sometimes patients with a genomic cause and those with a different cause may have very similar symptoms. We do constantly learn more about the ways in which genetic variants cause disease through research. Patients may have a gene variant causing their condition, but it’s so rare that it hasn’t yet been discovered, or so complex that it can’t be seen in the test analysis, so the test won’t identify the cause. Sometimes new understanding through research can then find the answer, which can be many years after the patient first developed symptoms. Naimah: And how are these tests performed? For example, are they a blood sample? Ellen: Yes, for most rare conditions, the tests use a blood sample. In cancers, a sample of the tumour needs to be tested after it’s removed by surgery or biopsy. The blood or the tumour is then processed to extract the DNA, and then there’s a r

Joey was diagnosed with DYRK1A syndrome at the age of 13, through the 100,000 Genomes Project. DYRK1A syndrome is a rare chromosomal disorder, caused by changes in the DYRK1A gene which causes a degree of developmental delay or learning difficulty. In today's episode, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, speaks to Joey's parents, Shaun Pye and Sarah Crawford, and Sarah Wynn, CEO of Unique, as they discuss Joey's story and how her diagnosis enabled them to connect with other parents of children with similar conditions through the charity Unique. Shaun and Sarah also discuss their role in writing the BBC television comedy drama series 'There She Goes' and how this has helped to shine a light on the rare condition community. Unique provides support, information and networking to families affected by rare chromosome and gene disorders. For more information and support visit Unique's website. You can read more about Joey's story on Genomics England's website. "Although we’re a group supporting families and patients, actually a big part of what we’re doing is around translating those complicated genetics terms, and trying to explain them to families, so they can understand the testing they’ve been offered, the results of testing, and really what the benefits and limitations of testing are...just knowing why it’s happened, being able to connect with others, being able to meet others, but actually often it doesn’t necessarily change treatment." You can download the transcript or read it below. Naimah: Welcome to the G Word. [Music] Sarah Crawford: But I would also say it’s okay to grieve the child that you didn’t have that you thought you were going to have. I just think that’s so important. And I think for me, the most difficult thing in the early couple of years was feeling like I couldn’t do that because nobody appreciated that I’d actually lost anything. [Music] Naimah: My name is Naimah Callachand and I’m head of product engagement and growth at Genomics England. On today’s episode, I’m joined by Shaun Pye and Sarah Crawford, who are parents of Joey, who was diagnosed with DYRK1A syndrome at the age of 13, and Sarah Wynn, CEO of Unique, a charity which provides support, information and networking to families affected by rare chromosome and gene disorders. Today, Shaun and Sarah are going to share Joey’s story, and discuss how their role in writing the BBC comedy drama There She Goes has helped to raise awareness of people with rare conditions in mainstream culture. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. So first of all, Shaun and Sarah, I wonder if you could tell us a bit about Joey and what she’s like. Shaun Pye: Yes. So, the medical stuff is that she’s got DYRK1A syndrome, which was diagnosed a few years ago, which means that she’s extremely learning disabled, nonverbal. Sarah Crawford: Yeah, autistic traits. Shaun Pye: Eating disorder, very challenging behaviour. She can be quite violent. She can be quite unpredictable. Doubly incontinent, let’s throw that in. She’s 17 but she obviously has a sort of childlike persona, I would say, you know. She sort of likes things that toddlers like, like toys and that sort of thing. But that’s the medical thing. What’s she like, she’s a vast mixture of different things. She can be infuriating, she can be obsessive, but she can be adorable. Occasionally, she can be very loving, especially to her mum. Sarah Crawford: She’s very strong willed, you know. Once she knows she wants something, it’s impossible to shift her, isn’t it? So, she’s got a lot of self-determination [laughter]. Shaun Pye: So, her obsession at the minute, or it’s fading slightly, which is quite funny, is that she’s become obsessed by – there’s a toy called a Whoozit that she loves, but she became obsessed by the idea of – she was typing buggy baby Whoozit into her iPad, so that’s how she communicates. She’s got quite good literacy skills. Sarah Crawford: Yeah. Shaun Pye: And we figured out eventually that what she wanted was she wanted her mum to take her to the park to find a buggy with a baby in it that also had a Whoozit in it that she could steal, and when Sarah explained to her at some length that it was not yours, she would say, “It’s not yours,” that drove her insane with excitement, at the idea that she could steal another child’s toy. So, it’s a good example of her because it’s funny, and, you know, it is funny, and she’s so cheeky about it and she flaps her hands, she’s very hand flappy, and she sort of giggles and she gets really excited, but, you know, the 2,000 time she asked to do that, and we have to walk to Mortlake Green near our house, and to the point where – again, it’s funny when it happens, but you get to the green and she doesn’t even look for the buggies anymore. So, that’s an example. But she’s a lot of different things, you know, and I suppose the thing

In this explainer episode, we’ve asked Clare Kennedy, Clinical Bioinformatician at Genomics England, to explain what the difference is between DNA and RNA, in less than 10 minutes. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on [email protected]. Want to find out more? Check out the blog 'Genomics 101: RNA vs DNA, what's the difference?' You can download the transcript or read it below. Naimah: What is the difference between DNA and RNA? Today, I’m joined by Clare Kennedy, who’s a Clinical Bioinformatician here at Genomics England, who’s going to tell us more. So first of all, Clare, what is DNA? Clare: So, DNA stands for deoxyribonucleic acid, and although this is quite a mouthful, DNA is essentially an instruction manual for our body on how to function, and a copy of this manual is stored within almost every cell of the body in a structure called the nucleus. So, our DNA essentially comprises all of the genetic information we inherit from our parents, and this information is contained within two long strands of code, and we inherit one strand of code from our mother and one from our father, and both strands combine and they form a twisted ladder like structure that we call the DNA double helix. So, each strand is made up of small units called nucleotides, and these nucleotides, they differ based on their chemical composition. They can either contain a molecule of adenine, guanine, cytosine or thiamine, and this is why we often see our DNA sequence represented by the letters A, G, C or T. And in total, our entire DNA sequence consists of three billion of these nucleotides. So, as this DNA instruction manual is quite long, it needs to be broken up into smaller sections that the body can read, and that’s where genes come in. So, a gene is a segment of the DNA and it contains a particular set of instructions, normally on how to make a protein. So, proteins are essential for life and they’re involved in almost every process within our body, and that is why we have around 20,000 protein coding genes in our DNA. Naimah: So then can you tell me, what is RNA and how does this differ from DNA? Clare: So, like DNA, RNA, which stands for ribonucleic acid, is an incredibly important molecule that encodes genetic information, and it’s found in all cells of the body. So, RNA consists of only a single strand of nucleotide units, and just like DNA, RNA can be represented by four letters that reflect the chemical composition of each nucleotide. These four letters do differ slightly though, because RNA contains uracil instead of thiamine, so you can distinguish a DNA sequence from an RNA sequence by the presence of the letter U and the absence of the letter T. So, while we think of the DNA as the instruction manual for the body that contains all of our genetic code, RNA is the reader of this instruction manual, and it helps the cell to carry out these instructions, so the proteins can be made. Naimah: So, can you tell me a bit more about this protein production, and how are DNA and RNA involved? Clare: So, protein production all starts in the nucleus with the DNA. So, if we want to make protein, we must first read the portion of the DNA or the gene that contains the instructions to make this protein. So, because DNA is so long, it’s really tightly packed into our nucleus, and the region we’re interested in might not be accessible, so we first need to open this region out. So, molecules and enzymes help us open this region of the DNA, and once the gene is accessible, they start to read it, and they start to transcribe the instructions that are encoded within the gene into a type of RNA called messenger RNA. So, as the name suggests, messenger RNA is the communicator of the instructions contained within our DNA, and this process is called transcription. So, the messenger RNA then leaves the nucleus and enters the main body of our cell, which is called the cytoplasm, and messenger RNA is transported to the ribosome. Now, the ribosome is a piece of machinery which will build the protein, and it’ll use the instructions that are encoded by the messenger RNA. But we need materials to build the protein, and that’s where a type of RNA called transfer RNA comes in. So, transfer RNA is instructed to hunt down the building blocks or the amino acids that we need to build the protein, and it brings these back to the ribosome. And then we have a third type of RNA that gets involved called ribosomal RNA. So, ribosomal RNA helps the ribosome assemble these amino acids into proteins in a process known as translation. So, it really is a group effort between the messenger RNA, the transfer RNA and the ribosomal RNA. And once the protein has been assembled, it might go through some more processing steps, and it’s eventually exported by the c

There are a range of outcomes from a genomic test. The results might provide a diagnosis, there may be a variant of uncertain significance, where a genetic variant is likely the cause of the condition, or there might be no particular gene found that is linked to the phenotype or clinical condition - also known as a "no primary finding" result. In this episode, our guests explore the impact of a "no primary finding" result on families, discussing the common experiences and expectations of parents and patients who undergo that genetic testing, and the role that hope plays in the experiences of children with rare and undiagnosed conditions. Today's host, Lisa Beaton, member of the Participant Panel at Genomics England is joined by Dr Celine Lewis, Principal Research Fellow in Genomics at UCL, Great Ormond Street Institute of Child Health, Jana Gurasashvili, a Genetic Counsellor, and Louise Fish, CEO of Genetic Alliance. "I think it’s also really important to add that hope isn’t necessarily lost when you don’t get a diagnostic result. And in a sense, what can be really helpful is for genetic counsellors to reframe that hope...sort of giving it a different context." For more information on the SWAN UK project which supports families with children that have been through genetic testing but have not found a result following that genetic testing, visit SWAN's website. Read more about the study by Jana Gurasashvili and Dr Celine Lewis: The disequilibrium of hope: a grounded theory analysis of parents' experiences of receiving a "no primary finding" result from genome sequencing. You can download the transcript or read it below. Lisa: Hello, welcome to the G Word. Lisa: I think in the back of my mind, subconsciously, I had hoped that when we eventually got a diagnosis, it would – I don’t know, bells and whistles, balloons going off, fireworks, etc. And then the experience of a letter thumping on the doormat, and I recognised the postmark quite quickly, and it was at that moment I suddenly thought, “Oh gosh, I haven’t buried all these feelings of hope.” Because I opened that letter with quite trembly hands, and then this diagnosis or lack of diagnosis, you know, nothing had been found, and it was a bit… I don’t know if it’s been described as like a nail in the coffin experience, because I really hadn’t realised I was still clinging to this hope all that time, and then again it was, you know, another, “No, nothing’s there. Lisa: My name is Lisa Beaton and I’m a member of the participant panel at Genomics England. On today’s episode, I’m joined by Dr Celine Lewis, the principal research fellow in Genomics at UCL, Great Ormond Street Institute of Child Health, Jana Gurasashvili, a genetic counsellor, and Louise Fish, the CEO of Genetic Alliance. Today we’ll be discussing the impact on parents with children with rare conditions, who received a no primary findings result after diagnostic whole genome sequencing. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. Can I ask all of us here present to introduce themselves, please? Celine: Hi everyone, I’m Celine, I’m a behavioural scientist in genomics at UCL Institute of Child Health, and I currently hold an NAHR advanced fellowship to look at the implementation of WGS, or whole genome sequencing, in the NHS. Jana: I’m Jana Gurasashvili and I’m a genetic counsellor at Northwest Thames Regional Genetic Service, and prior to that I was at Great Ormond Street, involved with consenting families to the 100,000 Genomes Project, and I also have an ongoing interest in the lived experience of patients and parents of genetic counselling and rare disease. Louise: Hi, I’m Louise Fish, I’m the chief executive of Genetic Alliance UK, and we are an alliance of around 230 charities and support groups that work with patients and families who have particular rare conditions. We also run a really longstanding project called SWAN UK, and SWAN stands for syndromes without a name. And the SWAN UK project supports families with children that have been through genetic testing but have not found a result following that genetic testing. So, it’s clear they have a genetic condition, but science hasn’t quite advanced far enough yet to tell us what that means and what that will mean for their child, and what that will mean for their family over the coming years. Lisa: And I personally can attest to the wonderful support that SWAN UK can offer because, as the parent of a still undiagnosed child, I have been involved myself with SWAN UK since my daughter was around the age of three to four years old. It’s brilliant being a part of my big SWAN UK family. We first realised that there were some – I suppose something wrong with our daughter when she was around two weeks of age, but it wasn’t something I could specifically put my finger on. I couldn’t at that point have taken her to a doctor and said, “I don’t know what’s wrong but there