Behind the Genes

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 podcast@genomicsengland.co.uk. 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,...

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 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...

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 podcast@genomicsengland.co.uk. 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...

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....

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: What do parents want to know about the Generation Study?How has design research shaped the Generation Study?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,...

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,...

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: Unlock GeneticsBAME visionpodcast 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...

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...

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 info@genomicsengland.co.uk. The episodes mentioned in the conversation are linked below. Hope for those with no primary findingsThe 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...

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 Hasting's 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...

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 GenomicsShining a light on rare conditionsHow 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...

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 info@genomicsengland.co.uk. 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....

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...

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 info@genomicsengland.co.uk. 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...

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 info@genomicsengland.co.uk. 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...

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...

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 info@genomicsengland.co.uk. 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...

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 info@genomicsengland.co.uk. 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...

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 info@genomicsengland.co.uk. 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...

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 info@genomicsengland.co.uk. 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.