The G Word

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 info@genomicsengland.co.uk. You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/005-What-is-genetic-or-genomic-testing.docx 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...

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 please visit the website. You can read more about Joey's story on our 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 read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Shining-a-light-on-rare-conditions.docx 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...

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 info@genomicsengland.co.uk. You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/004-What-is-the-difference-between-DNA-and-RNA.docx 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...

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." visit the websiteThe disequilibrium of hope: a grounded theory analysis of parents' experiences of receiving a "no primary finding" result from genome sequencing You can read the transcript below or down it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Hope-for-those-with-no-primary-findings.docx 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...

In this explainer episode, we’ve asked Helen Brittain, Clinical Lead for Rare Disease Diagnostics at Genomics England, to explain what a variant of uncertain significance is, 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 info@genomicsengland.co.uk. You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/What-is-a-variant-of-uncertain-significance.docx Naimah: What is a variant of uncertain significance? Today I’m joined by Helen Brittain, who’s the clinical lead for rare disease diagnostics at Genomics England, to find out more. So first of all, Helen, before we dive into the topic, I’d like to go one step further back and ask you to explain what is a gene? Helen: A gene is effectively a section of our DNA, which is our genetic code, and it contains an instruction, something important about how we grow, how we develop, how we function as a human. Humans in total have around 20,000 genes, which is our complete set of instructions, to tell us everything we need to know about ourselves. Naimah: So, what are gene variants then, and do they all have an effect? Helen: Variants are effectively differences within genes. So genes, like I said, are instructions, and they have a particular way that they’re spelled out and structured, so that the body can understand them and make sense of that instruction. A variant is where there’s something different about the way that that gene is spelled out or structured that could affect how it works, and basically a variant is a difference to what we expect to see. Naimah: And do all of these have an effect? Helen: So no, not all of them will have an effect. Some differences or variants within a gene may not affect the way it works at all, whereas others might alter that gene so significantly that it can’t do its job anymore, and could be very significant for that person’s health. Naimah: And how do we find these gene variants? Helen: Gene variants are exactly what we’re looking for when we’re trying to find a diagnosis for somebody. So, somebody with a rare condition is likely to have an underlying difference within their genes that would be the explanation for it. We’re finding these through doing genetic testing or genomic testing, so looking at an individual gene, a series of genes, or even across someone’s entire genetic code, through whole genome sequencing, and we find these variants through doing that testing. Naimah: And this might be a good opportunity to mention our other Genomics 101 episode on genetic testing, if you’d like to find out some more information on that as well. So, moving on with the next question, how is a variant’s significance determined? Helen: Variants, as we say, come from the genetic tests we undertake, and there are a team of people who look at and try to determine what effect that variant might have on that person. This is the majority of the time the work done within the laboratory teams, through the clinical scientists, who have expertise in understanding the impact of variants within a gene, and they work together with other clinical representatives, like the clinician looking after the patient, to understand that patient’s disease in as much detail as they can, to try to pull all of the information together and determine whether that variant is making a difference or not. They would look at a lot of different pieces of information to try to work out, could this be the reason behind that person’s genetic disorder? And that might be things like have we seen it before, can we predict the effect of that variant on the gene? And we have to understand how variants within that gene cause a condition to be able to match up against the variant that’s seen, as to...

29 February marks Rare Disease Day. This day is an opportunity for the rare community to come together to raise awareness of the common issues affecting those living with rare conditions. A rare condition is a condition that affects less than one in 2,000 in the population, and although rare conditions are individually rare they are collectively common. It is estimated that there are over 7,000 rare conditions. Around 80% of rare conditions have an identified genetic origin. In this episode of the G Word, our host Julia Vitarello, Founder and CEO of Mila’s Miracle Foundation, is joined by Rich Scott, Interim CEO for Genomics England, and Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England, as they discuss challenges for those living with a rare condition and the work being carried out across the genomics ecosystem to support them. Julia is the mother of Mila, a young girl who was diagnosed with a rare genetic condition called Batten Disease, and in this episode Julia takes us through Mila's story, and how she hopes to help many more families access treatments for their children. "So when parents, children, are diagnosed whether it’s a fatal or life-longing debilitating or difficult disease, if you know that what’s being learned from your child both from just the genomics to the potential treatments that’s helping the next child, that helps parents like me be able to continue living." You can find out more about Mila's story in our previous podcast episode with Rich Scott, Julia Vitarello and Dr Tim Yu. You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Rare-Disease-Day.docx Julia: Welcome to the G Word So my life at that point seemed to just disappear in that moment, all the things that had mattered to me were gone; I knew there was something wrong with my daughter but I had absolutely no idea that a typical child who was outgoing and active and verbal and had friends could suddenly lose all of her abilities and die. My name is Julia Vitarello, and I’m your host for today’s episode. Today joining me in conversation is Rich Scott, Interim CEO for Genomics England, and Ana Lisa Tavares, Clinical Lead for Rare Disease Research, also at Genomics England. Today we’ll be discussing challenges for those living with a rare condition and the work being carried out across the genomics ecosystem to support them. If you enjoy today’s episode, please like, share and rate the G Word on wherever you listen to your podcasts. The 29th of February marks rare disease day. This day is an opportunity for the rare community to come together to raise awareness of the common issues affecting those living with rare conditions. A rare condition is a condition that affects less than one in 2,000 in the population, and although rare conditions are individually rare they are collectively common. It is estimated that there are over 7,000 rare conditions. Around 80% of rare conditions have an identified genetic origin. Before I get into speaking with Rich and Ana Lisa, I wanted to share my story and my daughter, Mila’s, story. My life as a mother started really like anyone else’s, my daughter was perfectly healthy, her name is Mila. For the first three or four years of her life she was like any other kid. I live in Colorado in the United States, my daughter was a skier, she was a hiker, she was rock climbing, she was incredibly active and singing songs and swimming and riding bikes. But around four years’ old she started tripping and falling, she started pulling books and toys up closely to her face; she started being covered in bruises, getting stuck on words and repeating her sentences and I brought her to about 100 different doctors and therapists around the United States to try to figure out what was going on with her. Around four years’ old I started speaking with orthopaedic surgeons, with ophthalmologists, with neurologists, with speech...

In this explainer episode, we’ve asked David Bick, Principal Clinician for the Newborn Genomes Programme at Genomics England, to explain more about the Generation Study, in less than 10 minutes. For more information you can listen to our podcast episode where David discusses the conditions that we will initially look for in the 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 read the transcript below or download it here: What-is-the-generation-study.docx Naimah: What is the Generation Study? I'm Naimah Callachand, and today I'm joined by David Bick, the principal clinician for the Newborn Genomes Program at Genomics England, and he's going to explain more. Okay, so first of all, David, please, can you tell me what is the generation study? David: The Generation Study is a research study organised by Genomics England in partnership with the NHS. So what is the study exactly? We know that children are born every day with treatable genetic conditions. What we want to do in this study is we want to find those children and treat them before they become sick. We know that if we can find these children early in life, we can keep them healthy. Naimah: Can you tell me a bit about how the study was designed? David: Yes, this study was designed to look for genetic conditions that are treatable, and we went about looking for which conditions to include through an extensive evaluation that involves specialists, laboratory specialists, the NHS and patients from different support groups. And through this process, we identified more than 200 conditions that are treatable, and we are including those in the study. Naimah: And David, you mentioned the conditions list there. You can also find an additional podcast on our website where you go into more detail as to why the conditions on that list were chosen initially for the study. Can you tell me how this fits in with the current newborn screening program? David: The current newborn screening program looks for a smaller number of conditions, nine conditions. It has been extremely successful and is an extremely important program, and so we're looking to see how our program could be an adjunct to the current screening process. Naimah: How would people take part in this study? David: What we're going to do is we're going to ask couples in mid-trimester, in the middle of pregnancy to join in the study, we're going give them a number of opportunities to learn about the study and those that sign up. We plan to obtain cord blood from the placenta after birth. And as you may recall, the placenta is discarded and so this cord blood would normally simply be discarded, but we can take this umbilical cord blood and test it for genes. We expect it to expand to perhaps 40 trusts across the country. Naimah: And David, the NHS is already under quite a lot of pressure at the minute. What will this study mean for the NHS? What impact will it have? David: That has been one of the main concerns as we went forward with thinking about the study was to make sure that we did not add additional burden to the NHS. But it's important to realise that the children that we're looking for already have the condition, they're going to become ill. And our plan is, our hope is that if we can find them before they become ill, we will actually relieve stress on the NHS system. Let me give an example. There is a condition called biotinidase deficiency. Here is a condition where the child who has it, is unable to recycle a vitamin called biotin. Well, biotin is something you can pick up at the health food store, and so these children. Need to be given extra biotin every day. Very, very inexpensive, very, very safe. But if you don't find these children before they become ill,...

In January we saw experts from across the genomics ecosystem, including patients and those with an interest in genomics, gather at the Festival of Genomics - the UK's largest annual life sciences event. In this episode, our host, Vivienne Parry, Head of Engagement at Genomics England, speaks to Louise Fish, CEO of Genetic Alliance UK, and Professor Matt Brown, Chief Scientific Officer at Genomics England, to discuss the event and emerging future trends in genomics. In this episode you'll also hear some exciting future advances in genomics research from some eminent speakers at the Festival: "The scientific breakthroughs that are being made are absolutely incredible and they’re really exciting, but from the point of someone living with a genetic condition, what they want to see is those scientific breakthroughs making a real difference in the clinics...For some conditions, it’s about treatments, but it’s also about being able to get a diagnosis faster, to be able to understand what condition is impacting on you, how it might affect you over your lifetime and your wider family, and to be able to work with NHS services to understand and plan for the care and treatment that you’ll need throughout your lifetime." You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Insights-from-the-Festival-of-Genomics.docx Vivienne Parry: Hello and welcome to the G Word. Vivienne Parry: The Festival of Genomics is the UK’s biggest genomics event, and it’s become an essential part of our year. It’s free for 90% of its delegates, it’s in person, and with more than 5,000 people expected, it’s now so big that it’s had to move to ExCel’s cavernous Dockland Halls. It’s the place to hear top science and to spot new trends, but actually for me the joy of the festival is the people you meet. Of course, it’s great to catch up with old friends, but it’s the new collaborations sparked by random encounters at the festival which I think are the lifeblood of the genomics ecosystem, and everyone with an interest in genomics is here, patients, clinicians from the NHS, researchers, industry, policymakers, and the G Word. What we thought we’d do is bring you a flavour of this great event from the floor of the ExCel halls, and give you a quick soundbite from three of the speakers that we felt best exemplify the future of genomics. With me to discuss the event and future trends in genomics, Professor Matt Brown, Genomic England’s chief scientific officer, and Louise Fish, CEO of the Genetic Alliance UK, which as its name suggests, is an alliance of over 200 organisations reflecting the needs and concerns of those affected by genetic conditions. My name’s Vivienne Parry, I’m head of public engagement at Genomics England, and I’m delighted to be your host for today’s pod from the Festival of Genomics. Welcome to you both. So, let’s start with you, Matt. How important is the Festival of Genomics for genomics in the UK? Matt Brown: Well, the Festival of Genomics has become a really key meeting for the genomics community in the UK, and I think increasingly in Europe as well. It’s a really large, high quality event that brings together commercial and academic and biotech companies in the one forum, and I think it’s a really exciting programme. Vivienne Parry: And of course, Louise, it’s open to patients as well, which makes it an unusual event. Louise Fish: Absolutely, and it’s brilliant to have patients and families here. So, people living with genetic conditions clearly need to be part of the debate when we’re talking about developing new services, and developing new treatments and diagnostics, so it’s absolutely fantastic to be able to come together in one room with people from the NHS and the broader sector. Vivienne Parry: And it’s grown enormously, and I guess that reflects, as much as anything else, just how exciting genomics is. Matt, I’m going to pin you to the ground [laughter]...

In this explainer episode, we’ve asked Ana Lisa Tavares, Clinical Lead for rare disease research at Genomics England, to explain what a rare condition is, 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 info@genomicsengland.co.uk. You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/What-is-a-rare-condition.docx Naimah: What is a rare condition? Today I’m joined by Ana Lisa Tavares, Clinical Lead for rare disease research at Genomics England, and she’s going to explain more. Ana Lisa: There are thousands of rare conditions. I hesitate to say a number as we’re learning all the time, so this keeps changing. There are estimated to be perhaps around 10,000 different rare conditions, as an order of magnitude. Many rare conditions start in childhood, 75% or three quarters affect children. A little over 10% affect adults, only adults, and some, around 20% can start in children or adults. Naimah: So, what makes a condition rare? Ana Lisa: A rare condition can be defined as affecting less than one in 2,000 people in the general population. This is a definition that’s used in Europe. Different parts of the world use slightly different numbers and definitions, so for example, the number of people with a rare condition living in that country, there isn’t one single universal definition. The important part I think is that this is a practical way to help shine a spotlight on rare conditions, which collectively affect a lot of people, and the particular challenges in making diagnoses and finding treatments for rare conditions. So together, it’s estimated 7% of people are affected by a rare disease in their lifetime, or one in 17, so that means that there are 3 and a half million people in the UK affected by a rare disease, and in the world, probably somewhere between 250 to 450 million people, so perhaps 350 million people, a really huge number. When you look into these numbers, there are rare conditions that are much more common than others. So, 80% of people with a rare condition have one of the 150 most commonly occurring rare conditions. Cystic fibrosis would be an example that many people will have heard of, and if you look at those numbers from a different angle, 85% of rare conditions affect less than one in a million people, so are very rare, and it’s important to bring together these different voices to solve some of the common challenges. Naimah: Can you explain to me how these differ from more common conditions? Ana Lisa: The simplest answer is that they are defined by the frequency, so how often they happen in the general population, and one reason for grouping together thousands of rare conditions is to highlight some of the particular challenges. This includes delays in getting a correct diagnosis that can often take years, an increased chance of a misdiagnosis before getting to an accurate diagnosis, and treatment challenges, as 95% of rare conditions don’t have a specific treatment. This is a very good question, and I would like to note that it’s also an artificial distinction to some extent. So, human conditions have a range of underlying causes that can be broadly grouped together, including genetic and environmental, such as a viral infection. However, it gets complicated, for example, a proportion of common conditions that may have many different causes will have a genetic component, so for example causing an early onset familial form of a condition, such as diabetes. And in fact, genetic causes may give or can give the clue or the key that’s necessary to develop a new drug therapy that can then help many people with the condition, so those that may have a rare genetic cause and those that have a more common cause, such...

On this episode of the G Word, we delve into the promising advances that artificial intelligence (AI) brings to the world of genomics, exploring its potential to revolutionise patient care. Our guests discuss public perspectives on AI in genomics and address the ethical complexities that arise in this rapidly evolving field. Gain valuable insights into the future landscape of genomics and AI, as our experts discuss what to expect on the horizon. Our host Natalie Banner, Director of Ethics at Genomics England, is joined by Ismael Kherroubi García, member of the Participant Panel and Ethics Advisory Committee at Genomics England, and Francisco Azuaje, Director of Bioinformatics at Genomics England. “So, AI is already driving the development of personalised medicine for both research and healthcare purposes. [...] In the context of healthcare, we are talking about AI tools that can support the prioritisation, the ranking of genomic variants. To allow clinicians to make more accurate and faster diagnosis.” You can read the transcript below or download it here: Can-Artificial-Intelligence-accelerate-the-impact-of-genomics.docx Natalie Banner: Hello, and welcome to the G Word. In the past few years, artificial intelligence, or AI as a shorthand, has taken centre stage in the headlines. Sometimes for really exciting, positive reasons about the potential to drive improvements for society, and sometimes because of its potential risks and harms. These discussions and stories can sometimes seem like they're straight out of science fiction. There are a lot of questions, excitement, concerns about the societal impact of AI, so not just looking at individual patients, but that broader what does this mean for society? Ismael Kherroubi García: My somewhat hot take is that AI only accelerates societal impacts that genomics research and healthcare can have. So the impacts, of course, will be diverse and complex and quite widespread, especially given the quite nuance and sometimes difficult to understand areas of genomics and artificial intelligence. But the key takeaway from what I want to say is that it only accelerates the impacts of genomics and healthcare. So if we take genomics research to promote human flourishing, ideally, artificial intelligence will also only help further human flourishing. Conversely, applying artificial intelligence tools to genomics research can help perpetuate certain stereotypes and related harms. Natalie Banner: My name is Natalie Banner, and I'm the Director of Ethics at Genomics England. On today's episode I'm joined by Ismael Kherroubi García, member of the Participant Panel, and Ethics Advisory Committee at Genomics England. And Francisco Azuaje, Director of Bioinformatics at Genomics England. In today's episode we aim to cut through the hype and hyperbole and explore the real possibilities for AI within the domain of genomics and healthcare. We'll look at how AI tools and techniques have been used to date, and what the future holds, considering both the benefits and challenges faced in the genomics ecosystem. If you enjoy today's episode, we'd love your support. Please like, share, and rate us on wherever you listen to your podcasts. AI is in the news an awful lot, and not always for good reasons. There are many big and small tech companies that are exploring the use of AI in all walks of life, from finance to retail, to healthcare. And it's not always clear what AI means in these contexts, where it actually has the potential to really help people, drive improvements to healthcare and society, for example. But there are some exciting stories, so recently, Genomics England undertook a collaboration with DeepMind on their AlphaMissense tool, and that sought to classify the effects of 71 million missense mutations in the human genome. So it could process data at a scale and a speed far faster than any human has ever been able to before. So there's an awful lot of exciting work going on in AI, but...

In this instalment of The G Word, our guests engage in a compelling discussion centred around a recently published paper that supports the integration of whole genome sequencing into standard cancer care. Our guests shed light on the transformative potential of combining health data with whole genome data. Discover how this innovative approach empowers doctors to deliver more personalised and effective care. Our guests delve into the findings of a landmark national study, unravelling the significance of identifying inherited cancers for patients and their families. The episode explores not only the scientific advancements but also the real-world impact on individuals facing a cancer diagnosis. Our host Naimah Callachand is joined by Dr Nirupa Murugaesu, a Consultant in medical oncology at Guy's and St Thomas' NHS Foundation Trust, and the Principal Clinician for Cancer Genomics and Clinical Studies at Genomics England. And by Professor Sir Mark Caulfield, a Professor of Clinical Pharmacology at Queen Mary University of London, and who previously served as Chief Scientist for Genomics England and was instrumental in the delivery of the 100,000 Genomes Project. "In cancer we were sequencing sections of the tumour and comparing them to DNA inherited from your mum and dad, and that comparison allows us to work out what is driving the cancer, what may be affecting its potential for treatment and how we might choose treatments for patients. So this is a real opportunity to create precision cancer care." You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Whole-genome-sequencing-in-cancer-care.docx Naimah: Welcome to the G Word. What does it mean if we can test for inherited genes? Nirupa: It can influence how their cancer is treated. So it means that there may be certain types of therapy that are available if they have a specific inherited cancer gene, number one. It also can impact in terms of preventing further or other cancers related to those genes, and it may impact the type of surgery they have, and also the type of overall cancer treatment. And then finally, if they have got an inherited cancer, then, as I mentioned before, it may impact in terms of testing and screening for their family members. Naimah: I'm your host Naimah: Callachand. Today, I'm delighted to be joined by Dr Nirupa Murugaesu, who's a consultant in medical oncology at Guy's and St Thomas' NHS Foundation Trust, and the principal clinician for cancer genomics and clinical studies here at Genomics England. And Professor Sir Mark Caufield, who's a Professor of Clinical Pharmacology at Queen Mary University of London, and who previously served as chief scientist for Genomics England and was instrumental in the delivery of the 100,000 genomes project. Today, Mark and Nirupa are going to discuss key findings from a recent paper that's just been published in Nature. If you enjoy today's podcast, we'd really love your support. Please like, share and rate us on wherever you listen to your podcasts. Now, let's get into the interview. So first of all, Mark, I wondered if you could give me a bit of background on the 100,000 genomes project? Mark: So the 100,000 genomes project started in July 2013 following an announcement by the then prime minister, David Cameron, that the UK would be the first health system in the world to sequence 100,000 whole genomes, which is as much as you and I can read of the genetic code. In the case of cancer, which we focused on here, in cancer we were sequencing sections of the tumour and comparing them to DNA inherited from your mum and dad, and that comparison allows us to work out what is driving the cancer, what may be affecting its potential for treatment and how we might choose treatments for patients. So this is a real opportunity to create precision cancer care. Naimah: And Nirupa, can you tell me what the 100,000 genomes project meant for these...

As we approach the conclusion of 2023, we reflect on a year that not only signifies our 10-year anniversary but also marks another chapter of The G Word. Throughout the year, guests have joined us fortnightly to share their research, stories, and aspirations for the future of genomic healthcare. In this special end-of-year episode, Naimah Callachand sits down with Dr Rich Scott, Interim Chief Executive Officer at Genomics England, to look back on the last decade of Genomics England. Tune in as we revisit memorable moments from the 2023 podcast episodes through key quotes, reflecting on the transformative journey of Genomics England. Join us for this insightful recap and a glimpse into the exciting future ahead! Below are the links to the podcasts mentioned in this episode, in order of appearance: Public views on genetics - what have we learnt?Can genomics improve our understanding of childhood cancers?How can advances in genome sequencing support patients through their sarcoma journey?Which conditions will we look for initially in the Generation Study? What are the challenges of data governance in the digital age?The journey to the Human Genome Project and beyond with Dr Francis Collins “We’re also looking to the future where, as I say, we’re proud of the impact that there already has been, and the NHS Genomic Medicine Service is the first national healthcare system to offer whole genome sequencing and that is extraordinary. Thinking about how we can broaden our impact is a really important part of that, and that’s thinking about how we can be supportive of genomic technologies broader than just whole genome.” You can read the transcript below or download it here: Reflecting-on-2023-transcript.docx Naimah: Welcome to the G Word. Rich: We’re in an extraordinary time. The power to analyse genomic data has changed enormously. These are big changes in terms of the, sort of, analytics that AI could bring and the potential to work not just within the UK but with other countries and other big initiatives to make sure that we’re answering the questions as best we can. Naimah: I’m your host Naimah Callachand and today we’ll be hearing from Rich Scott, Interim CEO for Genomics England. He’ll be sharing insights with us from the last year, and we’ll be revisiting key moments from earlier podcasts in the year featuring some of the voices that have shaped our discussions. If you enjoyed today’s episode we would love your support, please like, share and rate us on wherever you listen to your podcasts. Now let’s get into the interview. So, this year we celebrated our ten-year anniversary and as 2023 comes to a close we want to reflect on our achievements not just in the last year but over the last ten. So, Rich first of all can you talk us through where we started in 2013 and where we are now? Rich: It’s amazing really to think about how much things have changed in terms of genomics in clinic and in hospitals and then for us as Genomics England over the last ten years. So, actually thinking back ten years ago was only ten years after the Human Genome Project was completed, and when one thinks about what one could do in clinic and those questions you could answer using genomics in clinic. We could see what was coming, we could see these new technologies, next generation sequence in coming, but it was much more dependent on very targeted testing. And now with, you know, our founding project, the 100,000 Genomes Project that Genomics England was founded to deliver in partnership with the NHS we asked the first big question if you like which was how can whole genome sequencing play a role in routine clinical care. And that’s now played out where evidence from the project, what we’ve learnt, the infrastructure we’ve built, and also evidence from around the world that through the NHS Genomics Medicine Service has now put that into practice and we’re working in partnership to help them deliver it. So, it has gone from an idea where...

On today's episode of the G Word, our guests will be discussing the CanGene-CanVar programme. Funded by Cancer Research UK, the 5-year programme aims to create an interface between NHS clinical care and research that will expand genetic testing access for those with inherited cancers. Our host Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England, is joined by Dr Helen Hanson, Consultant in cancer genetics at the Peninsular Regional Genetic Service, Kelly Kohut, Lead Genetic Counsellor at the South West Thames Centre for Genomics, and Rochelle Gold, Patient Representative on the CanGene-Canvar research programme and co-founder of BRCA Journey. "There is also the possibility of finding out genetic information that’s familial or inherited, which could mean that the information is not only important for the person who is being treated for cancer at the current time but also as a next step informing relatives that they might have a higher chance of getting cancers in the future due to a genetic variant..." You can read the transcript below or download it here: How-are-genetic-tests-transforming-cancer-prevention.docx Amanda: Hello and welcome to The G Word. My name is Amanda Pichini and I’m the Clinical Lead for Genetic Counselling at Genomics England. We know that cancer is a very common disease. About one in two people will develop cancer at some point in their lifetime. Cancer is a disease of the genome involving many changes to a person’s genome over time as well as other factors. Only a small proportion of all cancers are inherited, but this can have a significant impact for those families who have a much higher risk of cancer and options to reduce their risk. Today I’m delighted to be joined by Dr Helen Hanson, Consultant Clinical Geneticist; Kelly Kohut, Consultant Genetic Counsellor; and Rochelle Gold, Patient Representative and co-founder of BRCA Journey. We’ll be discussing the CanGene-CanVar programme which aims to link NHS clinical care and research to expand access to genetic testing and care for people with inherited cancers. Welcome, Rochelle, Helen and Kelly to The G Word. Thank you for joining me today. Let’s start with some introductions. Rochelle, over to you? Rochelle: Hi, everyone. I’m Rochelle and I’m one of the Patient Reps on the CanGene-CanVar research programme. I also co-founded an organisation called BRCA Journey that helps to raise awareness of the BRCA genetic mutation amongst both clinicians and the community, and also supports people who might be at risk of the mutation or who are thinking about testing, all the way through to maybe having preventative treatment or preventative surgery. We support those with that decisions. We’re not genetic counsellors but we do basically talk to people about our experience and knowledge that we have of what it’s like as a patient to be someone living with the mutation. Amanda: Thank you. Could you briefly tell us what BRCA is and how you came to be a patient? Rochelle: BRCA is a genetic mutation that puts people at greater risk of breast and ovarian cancer. My mum had the mutation, in fact she had two of the mutations which is apparently quite rare. She passed away from breast cancer and just before she passed away I found out that I had the genetic mutation as well. I personally have had preventative surgery and reconstruction to prevent myself from getting breast and ovarian cancer. I got involved in being a patient rep so that I can advocate for people who may have the mutation, but also make sure that as many people as possible can be tested and be aware that they have the mutation and have that power to have the knowledge to be able to do something about it should they so wish. Amanda: Thank you so much for sharing that with us. Kelly, over to you? Kelly: Hello, everyone. I’m Kelly Kohut, I’m the Lead Consultant Genetic Counsellor at the South West Thames Centre for Genomics, which is based at St George’s Hospital in...

This year as we celebrated our 10-year annivesary, the NHS celebrated a significant milestone of 75 years. In this episode we reflect on our journey over the last 10 years, including the impact of embedding genomic testing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today. Host Rebecca Middleton, Vice Chair of The Participant Panel at Genomics England is joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England in this special episode of the G Word. "To date, we’ve had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they’ve been given or make treatments available. That is a real positive benefit from that pipeline to individual patients." Listen to the other episodes in our 10-year series: patient journey has changed over the last 10 years for those living with rare conditions last decade of genomic research at Genomics England Transcript You can read the transcript below or download it here: Transforming-the-NHS-with-genomic-testing.docx Rebecca: Hello and welcome to the G Word. My name is Rebecca Middleton and I’m the Vice Chair of The Participant Panel at Genomics England. On today’s episode, I’m joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England. Today we’ll be reflecting on the last ten years of genomics, including the impact of embedding whole genome sequencing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today. If you’ve enjoyed today’s episode, we would love your support. Please like, share and rate us on wherever you listen to your podcasts. Thank you, Sue and Rich, for joining me today as we look back at how genomics has developed in the NHS over the past decade and impacted tens of thousands of lives. It all started with the creation of Genomics England and it’s first groundbreaking initiative, the 100,000 Genomes Project, which sequenced around 85,000 NHS patients affected by rare conditions or cancers and led to groundbreaking insights and discoveries for so many families. I’m one of those rare condition patients and my genome sits in the National Genomics Research Library besides thousands of others. Along with the project, I’ve been on a journey over the past ten years and I’m still hopeful that through time and further scientific discovery, my family and many others will get the answers they need for the future. Today is a chance to reflect back over the progress of the past ten years and to look forward about what’s next for genomics, for genomic science, the genomic service, and for the patients and families it impacts. Sue, welcome. If we can come to you first, and it’s a very big ask coming up, but can you briefly sum up your critical role in genomics over the past ten years and talk us through how you’ve shaped the service in the NHS to date? Sue: My role in genomics in the NHS has actually been much longer than ten years, because particularly genetic services have been part of the NHS journey since it was formed in 1948. As Chief Scientific Officer for England, part of my responsibility since I was first in that post in the Department of Health at that time and now subsequently in NHS England, but still with a crosscutting health and social care role, genetics and genomic services actually sit under the remit of the Chief Scientific Officer for England. Shortly after the...

Genetic Counsellors play an important part in healthcare and research. This Genetic Counsellor Awareness Day we focus on the role genetic counsellors have in research, to help improve care for patients and families. On this episode of the G Word, Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England, is joined by Emma Walters, member of the Participant Panel at Genomics England, and Jonathan Roberts, NHS Genetic Counsellor and Clinical Content Developer at Genomics England. Emma shares her personal story and our guests delve into the impact of not having access to genetic counselling. They explore how research priorities can be defined by bringing together both the genetic counsellors and what they're doing in their healthcare roles and the patients themselves and their experiences together. Johnathan will also be talking to genetic counsellors throughout this episode from the recent World Congress on Genetic Counselling. You can read the transcript here: Genetic-Counsellor-Awareness-Day.docx "I think another way in which research can really push that agenda forward is understanding who isn't accessing that [genetic] counselling. So when people get through the door and they experience genetic counselling, often that can be really valuable and they can suddenly start to make sense of all this testing, this family history. They can have a chance to talk about how they feel about it." With special thanks and acknowledgements to World Congress on Genetic Counselling and Wellcome Connecting Science for their contribution to this podcast including Genetic Counsellors, Manisha Chauhan, Alison McEwen, Jared Warde-Jospeh, Nour Chanouha, Jehannine Austin and Kennedy Borle.

Unfortunately, please note you may be able to hear some background noise or static during some parts of the recording. In this episode of the G Word, Candice King, Patient and Public Engagement Manager and Will Townley, Cohorts Manager who both work at the Diverse Data initiative at Genomics England, are joined by Dr Mie Rizig and Sir John Hardy, who both work at University College London (UCL). This podcast delves into a new paper published by Mie and John in the Lancet Neurology. The paper describes a novel African ancestry Parkinson's disease genetic risk factor. Our guests discuss the need for diversity in genetic research, the key findings from their study, and opportunities for future research in Parkinson's disease. You can read the full transcript here: Diversity-in-Parkinsons-research.docx “The number of people [in genomic research studies] from a white background, Northern Europeans, is about 95%. The number of people from an African background is only 0.2%. This is a significant disparity. When [clinicians] want to translate this into clinical practice, [they] think about: How will be able to test those people sufficiently enough?” The study was conducted by scientists from the UCL Queen Square Institute of Neurology, London, the National Institutes of Health, and the University of Lagos, Nigeria as part of the Global Parkinson's Genomic Program (GP2). GP2 is supported by the Aligning Science Across Parkinson's (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson's Research (MJFF). The paper mainly included cohorts from: International Parkinson's Disease Genomics Consortium (IPDGC) Africa

The Newborn Genomes Programme is delivering the Generation Study in partnership with the NHS. The study will explore the possibilities of whole genome sequencing in newborn babies, including to identify a wider range of rare genetic conditions current NHS newborn blood spot test. To do this, we have undertaken significant engagement work to identify the genetic conditions that should be looked for and fed back to families. In this episode of the G Word, Vivienne Parry, Head of Public Engagement at Genomics England, speaks to David Bick, Principal Clinician for Newborn Genomes Programme at Genomics England. They discuss the process behind determining the provisional list of over 200 conditions caused by genetic changes in more than 500 different genes and how this list may change during the course of the study as new evidence emerges. You can read the transcript here: Conditions-list-for-the-Generation-Study.docx You can also find a short explainer video explaining the conditions list on our YouTube channel.

In this episode of the G Word, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Dr Jack Bartram, consultant paediatric haematologist at Great Ormond Street Hospital (GOSH) for Children. Dr Bartram leads on molecular diagnostics within the haematology department at GOSH and has expertise in minimal residual disease in acute lymphoblastic leukaemia. He is currently the clinical lead for haematological malignancy genomics in the NHSE North London genomic laboratory hub and has been responsible for the implementation of advanced genomics and whole genome sequencing into clinical practice at GOSH. Approximately 2,000 children in the UK receive a childhood cancer diagnosis each year. However, childhood cancers account for a relatively small percentage (less than 1%) of all cancer diagnoses in the UK. This rarity has posed challenges in fully understanding the associated risk factors and underlying causes. In this podcast Dr Bartram discusses how genomics has emerged as a pivotal tool in enhancing our understanding, offering opportunities for precise diagnosis, personalised treatment, and improved screening methods for childhood cancer. You can read the transcript here: Childhood-cancer-awareness.docx "If I look back on and if I reflect on the last three years, we can probably accurately say for at least a quarter of patients it's [genomics] given us additional information, which has either aided in diagnosis or like I'd say to help re-stratify a patient or potentially reveal a target for a therapy that we didn't know of before."

This week on the G Word, our host Will Macken, is joined by a panel of Early Career Researcher (ECR) representatives to discuss how ECRs can navigate and position themselves within the ever-changing field of genomic research. Will is a clinician and researcher at the University College London Queen Square Institute of Neurology and Great Ormond Street Hospital. Will is also an ECR representative on the Genomics England Clinical Interpretation Partnership board. In this week's episode he's joined by: Medical Research Council "There can be people that just pick up basic skills to analyse the dataset that's in front of them that they've spent months in the wet lab trying to generate. Through to people who are proper software engineers and will be writing unit tests to test every single line of that code. I don't think it really matters where you sit on that continuum as long as it works for you, and it aligns with your future career progressions and what you want to be in the future, essentially." You can read the transcript here: Early-Career-Researchers.docx You can find the information on resources, events and support for ECRs mentioned on this podcast on our website. We've got free-to-attend monthly research seminars, and Research environment training sessions for those who have joined the Genomics England research community - find out more and register for our next sessions here. Email us if you have any questions: gecip-help@genomicengland.co.uk.

In this episode of the G Word, Lois Gulliford, Legal Counsel at Genomics England, is joined by Sarah Justine Kerruish, Chief Strategy Officer at Kheiron Medical, Hélène Guillaume Pabis, Founder and CEO of Wild.AI and Emilia Molimpakis, CEO and Founder of thymia, to discuss how to tackle bias in healthtech. With growing concerns about the safety of AI prompted by rapid technological advancements, a crucial question arises: how can we guarantee the equitable and unbiased utilisation of AI? Our guests delve into this issue and examine the importance of integrating diverse data sources. You can read the transcript here: How-can-we-overcome-bias-in-healthtech.docx "I think multimodal is the future, but we have a very special responsibility to be inclusive - to make sure that we are completely rigorous and robust in making sure that women and people from ethnic minorities are represented from the beginning and not as an afterthought."