DNA Today: A Genetics Podcast

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#179 Genetic Testing with Kira Dineen

by Kira Dineen
April 8th 2022

This week we’re bringing you a special episode of DNA Today! Our host, Kira Dineen, was recently a guest on The Science ... More

how is it that we find ourselves surrounded by such complexity, such elements we're all made of. Hi you're listening to DNA today a podcast and radio show where we discover new advances in the world of genetics from genetic technology like CRISPR to rare diseases to new research. We have you covered for a decade. DNA today has brought you the voices of leaders in genetics. I'm cured. I mean I'm a certified genetic counselor and your host. I was recently a guest on the Science of Everything podcast. The host, James and I had a fantastic discussion about genetic testing. This might be my favorite episode of a podcast I've ever been a guest on. Which is why James and I decided to also release the episode on the DNA today podcast feed. So to give you a teaser, we covered a range of genetic testing topics from the process and science behind the testing types of conditions that can be tested for And the difference between genotyping and sequencing.

We even discussed direct consumer genetic testing like 23 million ancestry including the potential and current uses for criminal justice. We speculated about social implications of the testing along with other futures that may be in store for genetic testing. So hope you enjoy this episode. If you do and you like James interview style and a school accent. Be sure to subscribe to the science of everything podcast. Welcome to the sides of everything podcast today we're doing a special episode. My guest today is Kira from DNA today and Kira, Welcome to the podcast. Well thank you so much James for having me on. So Karen tell us a bit about yourself and your podcast and sort of what you do over there. Sure. So my name is Chiara Deneen and I am a genetic counselor. Um So we'll get into kind of what a genetic counselor does, but in my role I meet with pregnant patients or patients that are looking to become pregnant in the near future. Um to talk about genetic testing and family history. So all kind of genetic conversations there. And then on DNA. Today, I'm the host and producer of the show. I've been doing that for 10 years. Um and it's it's been a blast. I talked to a lot of experts in genetics, talk to them about whatever they're researching or whatever they're an expert in.

So it's a really, really fun show and we've we've had a lot of episodes over the last 10 years. Um So it's it's a great way to just be active in the genetics community outside of direct patient care. Yeah, that's really cool. I um it's exciting to meet a fellow podcaster who's been going for so long. What motivated you originally to start the podcast and what sort of kept you going for so long in high school? I learned about genetics started to and I was like, well this seems like a cool area of biology and I was like, I want to do something in genetics but I don't know exactly what a career in genetics looks like. So I started by starting the podcast as a way to like explore different careers. Um and kind of get my feet wet with genetics and learn about genetic counseling through that and then was like, all right, I want to become a genetic counselor. And so the show really in some ways is kind of like for me advancing through my career of high school to college to graduate school. Um and now being, you know, actually full time employer employee um and genetic counseling and everything.

So it's a lot of interviews. When I started out, I truly did not know anything that the guest was going to set. It was like I was interviewing them for myself and there were some people that would listen. Um And now sometimes I have I have an idea of what the guest might say depending on what we're talking about. But yeah, it's it's just been really fun to be able to just network with so many people in the field. So I think that's what's kept me around and still producing episodes, but also just having a more engaging in larger audience as time goes on and becoming a business for myself too. So I think there's just a lot of ways that I just love podcasting and so I'm certainly kind of committed to the field at this point. Yeah, that's awesome. So today we're going to be talking about genetic testing sort of broadly and might branch out a little bit from there. This is sort of related to the area that you work in I guess. So tell us a bit about what is genetic testing. Yeah. So there's so many different types of genetic testing in general. When we're looking at genetic testing we want to see is there any genetic changes in a person that could increase their risk for a condition or that diagnosis them with a condition?

Um Or if there's a possibility that future Children biological Children of theirs could have a condition. Um So really being able to look at risk levels or give it a diagnosis. So with genetic testing we're looking directly at our D. N. A. So the code of life. And so we're looking at this code and saying okay is there anything that's different there? Um And if it's different does that mean that it's different and it makes something in the body not work or is it just the beautiful aspect of human diversity where everybody's a little bit different. So genetic testing is very interesting and it's it's come a long way in the last few years. So I think that's an interesting part just to look at it from a historical context of just how expensive it used to be in in how how you know inexpensive it is now. Yeah it's pretty crazy how much that technology has advanced and I want to talk a little bit more about that later. But I want to start with delving into some of the sides a little bit more. So we've talked about genetics a few times on the sides of everything podcast. I think it's been a while since I think it's been a little while since I did I did one.

And we haven't talked about genetic testing though, which is one of the reasons I thought this would be an interesting topic in addition to obviously that's that's what your background is. So one thing that we know is that, you know, D. N. A consists of a series of nucleic acids and we know that DNA codes for proteins which molecules that carry out many of the key functions in our body and that differences in in genes between different people can code for? Well, sometimes as you mentioned, just sort of fairly trivial or unimportant differences or sometimes they can code for disease traits or other other problem areas that there could be an issue for us. So one of the things that I wanted to ask about is sort of how genetic testing works. So it's obviously they take I assume it's a blood sample that they take. And I'm curious as to what sort of test exactly like so are they doing a full genetic genetic sequence or are they just looking for particular markers? Like tell us a bit about how that works. So it definitely depends on what the health care provider is ordering. And you said you know blood sample is usually a common way to collect a sample in order to actually perform the genetic testing. But a lot of testing can actually be done through saliva.

So some people might be familiar with like you get a kit um and you spit into it and send it off to a laboratory. So there's testing that you could just do through saliva because your cells throughout your body except for a couple exceptions all have the same D. N. A. In it. So I can have blood from a patient or saliva and I can do a lot of the same testing. Um Sometimes you need blood for a certain reason but in general for a lot of genetic testing you can have either. Um And usually saliva is a little bit easier to get. You know you don't need a phlebotomist for that. But your other question in terms of you know are we looking at entire genes? Are we looking at hot spots? Um It also you know depends on what the provider is ordering. So you know sometimes the largest genetic test is going to be the whole genome sequencing. So this is a test that is actually reading through all of your genes in your body. Um So this is I mean imagine how much data that is that's a lot of data to sort through. But that would be like the Biggest about three billion nucleotides.

Is that right? Yeah so that's that's a lot of letters straight through. Right. Um and the next you know the tier below that would be whole exon sequencing. So this is just looking at a small percentage about 1% of your DNA. That is actually active. It's being actively transcribed into M. RNA. And then translated into proteins. So these are the genes that are actually made into proteins um And actually doing something in your body directly. So a lot of testing now is is whole exon sequencing because we're like well let's just look at the active genes. Is there any any difference in those that we need to be aware of? Okay. Yeah this is really great. So a few more questions here. One that I have. Okay so two to about the source one about blood and one about saliva. So one thing that I've kind of wondered and I guess I could have looked this up I just sort of have never got around to it. Um You know when they take a blood sample and if they do some genetic tests on that are using that for. Um So forensic genetics or whatever where do they actually get the DNA from because a rich red blood cells don't have D.

N. A. So obviously they're not getting them from that. Is it is it the white blood cells like where does it actually come from? Yeah. You got it. So um as I said, there's some exceptions that some of our cells don't have all of our D. N. A. And as you brought up red blood cells don't you know they're they're different type of cell I guess. So what we're able to do in the laboratory and I've done this and it's it's cool that you're able to basically separate out that blood sample into red blood cells and white blood cells. So in the white blood cells you're able to actually get D. N. A. And process that. So that's the actual cells that are being analyzed. You know for for a lot of the testing. Especially in the lab I used to do what's called the stereotype. So that's a different type of genetic tests where we're actually looking at chromosomes. So our D. N. A. Is like the like bottom level. So going up from that chromosomes are made out of DNA and we have 46 chromosomes, 23 from our dad or biological father um and 23 from our our biological mother. So when I would do stereotypes and looking at someone's chromosomes, seeing if there's anything different there um you know I was I would break apart and Sarah I just want the red the white blood cells that Buffy coat layer when you kind of have the different layers in the tube and that's what we would use to actually look at the cells and look at the chromosomes.

So the layers come from central location. Is that right? Exactly. Yeah. So you spin it down. Yeah. So you just you know obviously there's a few steps to it. So um but you're spinning it down so that you're using gravity to separate the different blood cells. Yeah I have done I don't think I've worked with any human tissue before but I have done a little bit of that in the lab. I think it's interesting to sort of think through how how this works in practice. Um Okay so that's that's the blood tissue now about that saliva samples. So what what actual cells are in our saliva? I actually have no idea there. I assume saliva is mostly water. Which obviously that's not gonna have genetic material in it. So. Yeah. So where does the DNA come from there? So I think it's mostly just from like cheek cells. So sometimes like I know I've done um uh like a parentage testing where we're seeing, okay um is this biological father or not? Um In those tests we take a cheek swab. So we're actually taking like basically like a really long Q tip um and then going on the inside of their cheek and then swabbing each side for I don't know whatever it was like 10 60 seconds or something um For each side so that we're like trying to directly get cheek cells.

Um But you know one of the things with the saliva samples is you can't eat your drink including water for a half hour. So the reason for that is because we want to have more of your cells in your spit than water. Um Because sometimes the test will come back and say there wasn't enough DNA in the sample. And I'm like I feel like maybe that patient ate something you know, in the waiting room before and they're like no no it's fine. I've had nothing. You know or I send them home with a kid and they have something there like oh I'm sure it will be fine. But yeah because some some people ask me like oh is accuracy any different? They say no if we're able to get the D. N. A. There's no difference in accuracy. But sometimes we just don't have enough DNA to actually run the sample. So that's annoying. Well I've heard reports of various operations that require no eating or drinking for some amount of time beforehand. And some some patients seem to think that that's just like I don't know advisory or something that the doctors do just for the fun of it for some reason because they're just like oh no I just have a huge meal before this massive operation. It's like what are you doing? Like why now we got to reschedule that everybody's got a way to the hospital, whatever it is.

Yeah. Strange. Anyway, okay so that's so we can get genetic materials for blood sample or through cheek swabs or saliva. Um And we sort of mix the material get the cells we need and extract the DNA from that. So I have a question about whole exon sequencing because as you mentioned basically all the cells in our body have the same D. N. A. Few that don't have any DNA. But genetic material that's expressed is different in different cells. So if you're taking a whole exon sequence does that not depend on the type of cell that you're looking at? And is that important for um for any of these applications? Yeah that's a good question. So that is a whole another area of testing. So like epigenetic testing, looking at what genes are turned on and which are turned off that's gonna be very tissue dependent cell dependent. Um When we're looking at whole axum sequencing we're just looking at any genes in the genome the human genome. So it doesn't matter if okay my eyes are gonna have different genes turned on than my lips do because they look different. Right? Um They have different pigments.

Um So for whole excellent sequencing we're just looking at any genes that are active. We used to call the other 99% of the genome junk DNA. Like when I was in high school back in 2012 2013 we would say that was junk DNA. And I always wondered like how can it be junk? Like how can 99% of our DNA be junk. That just seems crazy. Um And later we found out all right, we're not gonna call it junk DNA anymore because that part of the genome actually does have roles in important roles, but it's just not actively becoming proteins. Um So it's more like regulatory roles or it's controlling other genes. So, you know when we're looking at whole exon sequencing, we're just like, all right, let's look at the active genes. So it's not necessarily active to that tissue. But just in terms of like in our bodies is it active? Yeah. Yeah. So that's a topic that I want to do an episode on probably fairly soon is the so called junk DNA or I guess non coding DNA I think is the preferred term now and as well as ePA genetics and control of gene expression.

Something that is still not very well understood. But there's a lot of work into that recently. one. Well, I mean this is a little bit of tension but I'm interested in your view on this because when you read about this sort of stuff, you'll see, well, you know, what is it one or 2% or so of the DNA actually codes for protein and then some other percentages are involved in control of gene expression regulation some some percentage of it's probably structural like keeping it in the right shape. But there's definitely a lot of other stuff in there like remnants of old viruses for example that have been inserted into the genome and repeats of short sequences that vary between people. I guess. This is just sort of a general question how much of the how much of the sequence kind of matters and how much of it is sort of this sort of evolutionary leftover if you like. I mean I know that that's not very we don't really know but I'm just curious what's your thought on that? Yeah I think it's interesting because we look at a technology like CRISPR. I don't know if you're familiar with the genetic editing technology. Um Yeah so basically what CRISPR is we discovered this naturally in bacteria um you know a little over 10 years ago um It was discovered before that but you know a lot of development started happening in 2012 with CRISPR.

But so basically what we found was that bacteria have this natural immune system where if they come across a virus as you said and alluded to they chop it up and then they keep it in their memory by putting it in their own D. N. A. So that when they come across it again they're like oh hey we've seen this before this is an invader now we know to get rid of it. Um So I think that that's interesting when we look at like the evolutionary process and that um you know, even like our mitochondria, one of our organelles are, you know, organelles like little organs in ourselves. You know, those used to be not there that that used to just be bacteria and then at some point, you know um became in ourselves very long time ago. So I I wonder from like an evolutionary standpoint as you're bringing up like our some of what's in our non coding DNA. Like it's it's part of that like old old viruses that we like fought a long time ago and are keeping track of that. Um Certainly not an area of expertise for me but I'm kind of like you I'm like that's an interesting area to like look at. Um and I wonder with crisper if that's going to be become more relevant and we're going to learn more about the non coding DNA.

And like what are the other purposes to it? Because there's been a lot of, you know, realization in the last 10 years of like okay it's not junk DNA. Um So what what are all the roles to it? Yeah. I think that it's um well I guess I don't know exactly what the popular perception might be but that people know that we've sequenced the human genome and I think that there's maybe a lack of understanding of how little of it we actually understand as to what it's even for. We're mostly studying a few percentages of it and there's a lot of mystery about what the rest of it does and yeah, we can read it but we can't understand all of it. Yeah. Yeah. And I think there's even a small percentage that either we recently finished or we still need to finish and like part of that non coding DNA Um that you know, when we were done with the Human Genome Project and it was like a big deal that it was it was a draft, it wasn't like 100% complete. Yes. I'm still not sure exactly where we are now. I know there are some highly repetitive sections which are very hard to sequence because you can't figure out how many it's difficult to figure out how many repeats there are when it's just the same thing over again, I don't know exactly what the status of that is.

Um Right. I think that's a lot of in like the telomeres are the ends of the chromosomes. Next question I have is sort of related to this, that there's sort of two terms that one might hear in this space genotyping and gene sequencing. What's the difference between those? Yeah, that is a great question and one that I asked a lot of labs um when I'm looking at like what should I order from like some of my questions in terms of understanding like what are they actually doing in the lab. So genetic sequencing is what we were talking about earlier with, we're going to read through this entire gene and we're gonna see. Is there any differences in that gene now genotyping is we're just gonna look at little hot spots on the gene. So sometimes I think of it like a highway. And if we're doing genetic sequencing, we're driving down the entire highway now with genotyping, we're only going to pop in on the exits. So we're not gonna actually drive through, we're just popping in on the exits. Um like looking at hot spots. So a lot of genetic testing when we were starting with this and years ago, a lot of it was genotyping because we'd say, well, we know the most common mutations um which we also call pathogenic variants.

That's more of a scientific term now for a mutation. So we used to say, all right, well this is the most computations. Let's just look for that. Let's not just let's not take the time to look through the entire gene and there's advantages to that? Obviously it's gonna be cheaper if you're just looking at certain spots on the gene, but there's a lot of disadvantages because what if there's a mutation elsewhere on the gene and you're gonna miss that because you're not even gonna look for it. So I think that's something that's changing a lot. I still see some providers ordering genotyping, but that's not something that I do anymore because to me the technology is beyond that. Let's sequence the entire gene for the ones that we're ordering. So um just a point of clarification here, you're talking about sequencing an entire gene. So it is the way it works. You order a set of specific genes that are then sequenced. You don't sequence the whole genome or even the whole x. Um You're just looking at a set number of genes but you sequence that entire gene. Is that how it works? Right? So it depends what someone orders. So if if we were ordering a whole axum then we're just going to be sequencing all of the active genes as we talked about whole genome everything.

We're going to see what's everything. And then you know I haven't ordered any of those only as a student. You know, certainly looking at doctors and other genetic counselors doing that. But for me I've ordered genetic panels. So that's selecting specific genes that I'm gonna have. My patient be sequenced for for those certain genes. Um And that's because I work in prenatal. So when I'm doing carrier screening I'm looking at the parents to see okay, are there carryover condition like cystic fibrosis, sickle cell. Um I want to sequence those genes. I'm not gonna I don't care about the rest because I'm in a prenatal setting um that could change in the future. Um But yeah it definitely depends on like why you're ordering the test, what you're looking for. Did you know perkinelmer genomics was one of the first laboratories to offer whole genome sequencing on a clinical basis. Whole genome sequencing can maximize clinical diagnostic yield for patients. But the turnaround time of six weeks perkin Elmer's whole genome sequencing test is designed to provide access to additional valuable information compared to an ex um perkinelmer genomics provides one of the world's most comprehensive programs for detecting clinically significant genomic changes.

Perkinelmer genomics delivers knowledge that can empower health. Perkinelmer is a global leader committed to innovating for a healthier world during their mission at Perkinelmer genomics dot com. Also listen back to episode 1 76 with Perkin Elmer's dr Madhuri Hegde where we explored the power of whole genome sequencing, discover all that perkinelmer genomics has to offer at Perkinelmer genomics dot com. Do you know the power of apologetic risk or apologetic risk or or pr ess enables healthcare providers to more effectively help patients lower their risk of life threatening diseases. With the latest breakthrough in clinical genomics. Ally Luca has launched the first PRS test on the market to calculate ancestry specific PRS for breast cancer prostate cancer coronary artery disease. Type two diabetes and Alzheimer's disease and delivers the results in a clinical grade report the PRS test is a laboratory developed test that is performed in a clear certified C. I. P. Accredited genetics lab here's just one example of why this test is so important. If a patient with breast cancer test negative for BRC one BRC two genetic mutations Lillikas PRS test may be able to identify other key genetic mutations which played a role in the cancer development.

Learn more about PRS in our previous interview with Silica Ceo and co founder Gordon? Oh botha. On episode 1 68 of DNA today you can order the PRS test at order dot A L L E L I C A dot com for 25% off and free shipping. Use code DNA today to check out silica empowering the next generation of clinical genomics. Yeah. So just for some for some context here, well you might know the number better than I do. So the current estimate for the number of genes that humans have, the number I have in my head is 30,000. Is that it's Around like 20.30,000. Yeah, that sounds Right. I've seen scenes of different estimates. I recall that before the Human Genome Project. People scientists estimate it was much higher. Like 100,000. But then it was discovered that they were actually far fewer than they'd expected. Which is always interesting how we really thought highly of ourselves. Like we must have so many genes because they were comparing it off of other genomes too. And they were like, well if this animal has this many genes were way more complex, we must have way more.

And then we were like, oh we don't. So it was a bit of like a humbling moment I think for the human race. Yes, partly. Although I guess again this is a little speculative, my kind of take on that. Is that probably control of gene expression, genetic regulation is doing a lot more of the work than we thought, I guess naively it's like to do more things. You need more genes, but maybe it's actually just that you have more complex and intricate control of the Yeah, I think you're on the right track there because otherwise we would have that correlation between like alright, if if a um animal is more complex than they must have more genes, but it's like we even see with like fruit, like certain fruit have like crazy amount of chromosomes and we're like alright, so there's something that we're not quite understanding there and yeah, it's probably lies in epi genetics there. Yeah. Anyway, so just coming back to what we were talking about before, so yeah, if there's about three billion nucleotides then and if you do a whole genome sequence then obviously that's a lot um whole exon sequences, but that's about 1% of that. So that would be What's that? 30,000? I think. Sorry, 30 million.

Um And then um it's easy to get the orders of magnitudes wrong. And then if we've got about 30,000 genes, so you pick a few of those and sequence those. Gene is I don't know, 1000 few 100 long depending on obviously it varies by the genes. So that's just giving a bit of a framework for people to think about the numbers we're talking about here. So obviously it varies depending on exactly what you're ordering the test for and what the purpose of that is. And actually that makes a good move to the next question which is applications of genetic testing. So so far we've been talking about the science of it and how it's done. We've mentioned sort of vaguely that there's various health applications. But let's look at that a bit more specifically. So what are some of the reasons why medical practitioners would want to order genetic testing? And also there's the new field of direct to consumer genetic testing which I want to talk a bit about as well. So what are some of the, what are some of the applications there? Yeah. So there's so many areas of healthcare where we're ordering genetic testing um I can speak to my area first then kind of fan out from there. So as a prenatal genetic counselor I kind of mentioned before. Alright, a panel of genes. So if I was doing carrier screening for someone that's pregnant and their partner for that, I'd be looking to see, are there a carrier of the same condition?

Um So these are awesome. A recessive conditions for the most part and I'm looking to see uh for those conditions and for most we have two copies of each gene. So if one copy doesn't work, then that person is a carrier of that condition, they have a backup copy. So there for the most part healthy, they probably don't have symptoms from it. If both a patient and their partner um or the sperm donor, egg donor. Whatever the situation is, if they are also a carrier for that same condition, they have a chance for passing that down um to a baby um where a baby could inherit both of those non working copies that have a mutation and then baby has no working copies and has the condition. So with carrier screening, I'm looking to see is that are they carrier for anything? And you know, are the couple matching for a condition? Um So that's a case where we're not nobody has a disease, nobody has a condition. But we're, you know, more doing on the preventative side. So again, that's like more of the gene panel. Yeah, just just to clarify with that.

So the well the way I think about is the key issue there is that parents can be a carrier for a condition that they don't themselves exhibit. So that that's that we talked about between genotype, which is their genes in the phenotype, which is the characteristics that they express. And so they may have no idea that their carriers for a particular condition. But potentially if say they're both carriers and it's a recessive condition. Then if they both pass that copy of the gene on to their child then the child could exhibit the trade. So that's the sort of thing that we can test for genetically that there's not really any other way to check for. Right. And and as you said, most people don't realize they're a carrier for a condition because most times carriers don't have any symptoms. Um So some people might say like oh well I'm healthy. Like I don't I don't see the point of doing carrier screening. They say well most people if we if we look at enough conditions, most people are a carrier for something because we're you know we're testing for hundreds of conditions for only testing for a couple. Alright you're probably not a carrier for those. Um But the more conditions we're looking at the more likely you're a carrier for something. Usually it's different from your partner but sometimes it's not which is why we do the testing.

Sorry go ahead. You were then going to talk about other. Yeah so um another application that I order is um for people that are pregnant um There's a test called noninvasive prenatal screening and this is really cool because we found out that coming off the placenta ourselves that flow in the pregnant person's bloodstream and those cells tend to pop open and release the D. N. A. So by taking a blood sample we can isolate that D. N. A. And then screen for genetic conditions and these are random conditions not inherited. Like I have been talking about carrier screening. So these are random conditions most commonly down syndrome where we have an extra chromosome 21. So it's a really interesting technology that you know we discovered like wow there's actually cells from the placenta in the pregnant person. What if what if we can use that to screen for conditions? So that's a test that um has become much more popular. It was clinically available about 10 years ago but the last few years has become much more popular. Yes.

So for these, so we talked about inherited genetically inherited traits which you can check the mother and the father to see whether that was likely to be an issue. But unfortunately that it doesn't stop there because there's also the possibility of genetic mutation where basically random events can happen which can then lead to uh characteristics, disease states in the offspring. And so what you're saying is that there are they're actually um there's genetic material which enters the bloodstream of the mother during pregnancy which we can then test for and see if there are any of these conditions in the offspring. One question I have is if there are I think this is actually a broader issue which I confess. I don't fully understand. How does that work with respect to the mother's immune system? If there's foreign material, would that be attacked by the mother's immune response or is that suppressed during pregnancy? I'm not quite sure how all that works. Yeah that's a good question. So during pregnancy um the body does have a lower immune response because otherwise we'd probably fight the pregnancy because our body would be like what are all these cells growing? Like thinking like is it cancer? Right. So in general your immune system is lower during pregnancy.

Um But yeah I'm also a little curious because I don't I don't fully understand like how we can have cells in us that are not ours. I mean 50% of it is our genetics if it's our biological child. Um And our genetic child. Um But what's interesting is that the cell free DNA. So when a cell pops open and releases the D. N. A. That is after um a person gives birth. That clears from their system very quickly. I've heard like ours like that quickly but the cells that are still intact that can stay in a person's body for for years. Um Yeah so I remember I was reading a book by carl Zimmer and she has her mother's laugh and I ended up interviewing him on my show. And I just remember being amazed talk it was talking about some case where they were able to find in people that they had for people that are 46 X. X. So like a traditional female stereotype that they were able to find some why cells some cells that had the Y.

Chromosome and they're like well what is this? And they're finding the origin was um those people's uh sons from previous pregnancies um that their cells were still there and I was like that still amazes me to this day. And I read this book like four years ago. I've never heard of that before. Yeah. Isn't that wild? But the technology takes advantage of the self free D. N. A. That's how it works. So if we were looking at cells that are intact it wouldn't it would fall through it. We wouldn't be able to test it. Yeah. That's really interesting. Um Okay so so far we've got testing for recessive conditions and parents and also testing residual DNA from pregnancy. What other applications are there for the next screening? Yeah. So going outside of my practice in the cancer realm we can look at genes that are known to protect us from cancer. If there's a pathogenic variant or mutation in one of those genes, it lowers our protection for cancer. So then in turn it increases our risk to develop cancer.

So far protection for cancer is lower. We're naturally going to be more likely to develop cancer. So there are certain genes that we can look for. The most common is B. R. C. A. One and two. So these are genes that people may know because of Angelina Jolie a few years ago was in the news because she shared that she has a pathogenic variant in A. B. R. C. A. Gene and ended up having preventative surgery so that she was reducing her risk to develop cancer. Um So I think that's one that some people might have heard of before. And so yeah cancer is an interesting area because that's another area where You can either be doing it preventatively. So say your mom had breast cancer at 35. You're like okay well I that to me that that's high risk. Let me see if I have a genetic change in me that also increases my risk for breast cancer. And then you can also be doing it after you're diagnosed with cancer so that we understand okay what what led to the cancer to happen. So that's that's a test where we can do it both ways. Yeah. Right. I want to talk a little bit more about that before.

Maybe moving on. There are a couple of other issues that I just wanted to mention. So people listeners are probably also familiar with other uses of genetic testing. I guess it still counts as genetic testing. It's not diagnostic testing though. So this would include for forensic use like in terms of for solving criminal cases. Um as well as for genealogical tests which are increasingly popular for people find out about their ancestry and for paternity testing which is obviously when people will be familiar with and and for those usage for those usages at least for forensic and paternity. My understanding is that we only need a relatively small number of markers which vary between persons and that that doesn't need. I think those aren't even genetic markers in the sense that well, in the sense that they're from genes, I think that they're just from non coding DNA. Um, but just sufficient to basically identify persons. So it's rather different from the diagnostic testing. I know that that's not what you work on. I thought I just mentioned that because listeners may also be thinking about that. But yeah, all of these applications have increased dramatically in recent years because of the development of technology. So now I wanted to ask you a question about direct to consumer genetic testing which has expanded very rapidly in recent years.

So this is when consumers directly order various genetic tests from various private companies, not not like directly or necessarily through a medical practitioner. So, certain companies have come under criticism for making claims about the medical benefits or applications of these sorts of tests. And it's it's a tricky area partly because in many cases it's sort of not known whether or not there's any medical medically actionable benefit from knowing whether you're predisposed to a particular condition or because often we're talking about probabilities in these cases that having this variant slightly increases your risk of this type of cancer and so forth. And that sort of information is is sort of quite abstract and often difficult for people to, well it's often difficult for enough for medical practitioners to understand, let alone people who don't have that sort of training. So I'm just interested, what are your sort of thoughts about this sort of direct to consumer health focused genetic testing And some of the issues surrounding that it's difficult because a lot of people don't fully understand what the testing can tell you and what it can't tell you. I think if people understood that, I'd have a lot less issues with the direct consumer testing.

And there's even a testing that is like in between medical grade and direct consumer where people can order themselves, but there's a health care provider directly involved with them. So it's kind of like a middle ground too. But for these direct consumer where you buy the kit, it either gets shipped to your house, you're picking it up at target walmart wherever. Um and you're just sending it off and then you get results in your email or through a portal and there's no person telling you results. So all those direct consumer, um I think it's it's important to know that it's it's not gonna be as extensive as testing you're gonna get with a health care provider. So using the breast cancer genes that I was talking about before B. R. C. A. One and two. I think that's a good example because you know, and I'll be frank at 23 me does a test will test for these jeans. Um And a lot of people know this company is one of the biggest direct consumer companies. Press coverage. Yeah. Yeah, definitely. And and and so with the B R. C. A jeans, they do genotyping like we talked about. So they look at the three most common mutations in B.

R. C. A jeans. Now. These are mutations that are common in the Ashkenazi jewish population. And the problem I have with it is if a person does the testing and it comes back negative, like, okay, didn't find any mutations, they may not understand that. It's just that they don't have those three mutations. It didn't look at the rest, they could have a different mutation that B. R. C. A gene and think now, oh I'm negative. So I think if people understood that and said, okay, well I'm only negative for these three mutations maybe now I want to go and see a healthcare provider to see do I have a mutation elsewhere in these jeans or a different genes related to breast, ovarian cancer, prostate cancer, all of that. Um So I think it's there's a time and a place for it. Um you know, I think the ancestry is very interesting as well, but it's also something that there's a there's a big discrepancy between people of european descent and people of non european descent. We have a lot more in databases for people of european descent because that's how genetics started. We started with a lot of european genomes.

So we understand those variants better. We understand the spelling of those genes better. But if someone is of non european descent, the ancestor results, they'll get back is going to be much more general. So I'm of european ancestry and and one of, you know, branches my family's from Ireland, my testing gets so specific to say I'm from east cork Ireland. So it's very specific. Right? And lucky for me that lines up with family stories, I don't have to tell anyone, oh, we're actually not from there. Which is a whole another thing. Right. But, you know, people have more recent african ancestry, it's probably gonna give them more of a general you're from this area and not necessarily pinpointing, you know, to a certain county or something. So, you know, and this is an area that is, you know, we have huge, huge diversity issues in all genetic testing because of that ancestry people are more familiar with. But this is a problem where we have these genetic changes and we don't understand, okay, is this making the gene not work or is it human diversity because our research pools are lacking diversity.

Yeah, and it's quite difficult because there are many genes and many variations on those genes and many possible conditions. And also as we sort of mentioned for a lot of, especially things like cancer and heart disease and and so forth. It's not like one. And I think people don't understand this. It's generally not the case that a particular variant is definitely going to give you a particular disease. There are some diseases like that. But for the most part it doesn't work that way. And it's it's an issue of, well, it increases the risk or possibly decreases risk by a certain amount. Um, and and the thing is that it gets even more complicated in that because it could be an environmental interaction. So it may be for instance that if you're just making this example, but if you're a smoker, it increases your risk of certain types of cancers, but not if you're not a smoker or if you have a poor diet, it increases risk. But for people with a good diet, maybe it doesn't. And so this sort of information is very difficult. As I said, even for medical practitioners to understand, let alone non sort of lay person. So I guess I have a concern about how actionable some of this medical information is. So, you know, if I found out that I was at a bit of a higher risk to develop certain types of cancer or heart disease, it's sort of not clear to me what I would do other than, you know, eat healthy exercise.

And the usual advice anyway. So I mean I gather that probably for some conditions, there are, There is actionable medical advice I know that there's a list of about 60 variants that I forget the organization in the in the us. They've recommended that the AMG AMG and in the US at least I'm less familiar with Australia. I don't know that the case is probably similar but that they just to give a bit of background. So there's a further complication here in terms of we've been talking about whether someone seeks out this genetic information but there's a there's a further issue that if a diagnostic test has been conducted for some other reason and they sequenced a bunch of genes or the whole genome or whatever and they find other variations. Should they tell the patient the issue? Is there? Well if if it's important you should tell them. But How do you quantify important? Like is it medically actionable? What's the risk and things like that? And we often don't have very good data. So so there's this list of around 60 particular variations that as I understand it's recommended. I don't know that they're legally they have to but I think it's a recommendation that they be reported. I don't know a lot about though what medical actions sort of can be taken on those.

So what's your knowledge on that or just general thoughts. Yeah. So usually that's coming up and it's the if I'm remembering right a CMG 59 genes. It could have been updated since the last time I looked at it because I haven't been in that area for a bit. But so if someone's doing that whole axum sequencing that we talked about our whole genome and they find a pathogenic variant mutation in one of these 59 or so genes. Then hopefully ahead of time the patient has sat with the health care provider and decided if something comes up in one of those jeans, they either want to know about it or don't want to know about it. So hopefully they had informed consent before they even got results if they decided they wanted to know about it. Some of these genes might be as we talked about like a B. R. C. A. Gene mutation where, okay they have an increased risk for breast cancer or ovarian cancer prostate cancer. Um So it's it's different cancer risk there. And so in those situations people can have the option of doing more screening. So for breast cancer um they might be doing breast MRI's ultrasounds, possibly mammograms definitely.

Um So that they're screened more regularly than someone that has an average risk for breast cancer. There's also options to have as I mentioned with Angelina Jolie of having preventative surgeries so to remove breast tissue before you even possibly develop cancer just to reduce your risk and you might never have developed breast cancer in your life. But some people look at it. Well I have an 85% chance. Alright that's pretty high. Some people decide to to do um the preventative surgery. So that's called a prophylactic bilateral mastectomy. Um So very long games. It it took me years, I have to say to get all the lingo down and pronounce it right and everything. But um so there's certainly for some, some conditions and some some genes that we find a mutation, there are actions we can do to either reduce our risk or to know like you have this diagnosis, you may want to plan something in your life of if you know that you're at higher risk of developing a condition. Yeah, I think I guess each patient is going to be different there.

I think that the difficulty is in getting informed consent because it's hard to give the relevant information to people. To understand all of these sorts of risk. For me personally, and again, this is just sort of my view. I probably wouldn't want to know about any condition unless it was something that I could do something about. I mean, I suppose there's always a question like, well, if you knew you were going to die on this particular day, would you want to know that that's an issue? But more generally, I feel like probably this is gonna be true for a lot of people that there's a question about increased worry and stress, if if they think that they have a risk for something, especially if the increased risk is maybe marginal compared to lifestyle choices, which I think is the factor that people, I think overestimate the effect of genetics. I don't actually know if there's no data on this but choices. And I think that that's something that the medical field is sort of trying to be more cognizant obviously is doing more about sort of encouraging positive lifestyle changes instead of just focusing on the genetics. Obviously though that that plays a role and they can interact as as we mentioned before. But yeah, so, but there are some cases where action can be taken and in that case then this is useful.

I think that there's also people have a perception many patients always they have a perception that information is always good and it's good to know it's good to screen and things like that. But increasingly I think the medical community is coming to realize that often that's actually not the case. For example, if conditions have a very high if if the condition has a high, relatively high baseline relative to the sensitivity and specificity of the test, then you can get a large number of false negatives and then you can end up spending large amounts of money and time and stress getting tests and biopsies and scans and whatever for conditions that you don't actually have or for which the risk is relatively small and and all of these things have costs associated with them. So there's there's a balancing act there about how medically useful information is and what the risk is balanced against the costs and and this stress. And I guess I would add as well just sort of attention taken away from things that might be more helpful like, like lifestyle improvements. Right. Yes. Yeah, definitely. And I think another aspect of that is like looking at an informed consent, like in our health care systems, we don't necessarily have time to sit with a patient.

I mean back when I was a student and I was observing genetic counselors, um, consenting patients into doing this whole genome, whole X. Um, I mean it would take a long time to say, okay, do you want to know this? Do you want to know that? Like this is how the testing works. This is what could come up. Are you sure you want to do this? Um, and I think it is really important to have informed consent because when I sit down and talk with patients about as we talked about in the prenatal setting, carrier screening and the noninvasive prenatal screening. You know, I talk it through and I say, this is what we could find out, patients will say, all right, what do I do with this information? We talk that through. And sometimes at the end of our conversation, patients say, well, thanks for going through all that. I'm glad we did because I don't want this testing. And I'm like got it too because other places might just draw their blood and say we'll let you know and they don't even know what they're getting. So I think it's so important that we take the time we make sure a patient understands what the testing is and that they actually want to do it. Because the last thing I want to do is make a decision for a patient.

That's not my job. My job is to educate the patient and help them make a decision that's best for them and their family. Yeah. One of the things that we talked about on the sides of everything before is different cognitive psychological biases. And I think that it's interesting how those potentially interact in the health space about people's estimates of risk and the value of information and things like that. So I think going forward we're going to need a lot better research that sort of looks at things from this disappointing point of view about how people respond to information and how they, you know, what sort of medical information they seek out and what sort of motivating to people and actually is sort of helpful for them and what isn't. So I think that there's I guess broadly the genetic age is only, well I don't know if you data from the beginning of the from the sequencing of the human genome by 20 years years old, we're still sort of learning how to do an information rich genetics agent. I think that going forward will hopefully develop, develop better systems and get sort of used to having this information. But until then I think we're just sort of were groping around a bit and trying to work out how to how to do it well. Yeah I think so, palla genic risk scores or PRS are a powerful way to identify an individual's risk of common disease.

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New episodes drop every Wednesday. So before we finish up, well I guess that actually leads well into the last question. What do you think about the future of genetic testing techniques and genetic screening And also future applications as technology changes and develops? It's obviously changed a lot even over the last 10 years. So what do you think is going to happen in the future. Right. I think in terms of how we're changing with genetic testing. I do think that a lot more people are going to get either whole XOM sequencing or whole genome sequencing because a lot of the testing is okay we'll do a gene panel, we'll look at these certain genes but over time isn't it going to be more cost effective as we were mentioning earlier to just look at everything and then keep referring back to that over that person's life. So you know, if someone's young say, alright let's sequence their genome, let's sequence their ex. Um And then we can keep referring back to that instead of throughout their life. Keep ordering different genetic tests. I think we're going to get to a point where genetic testing has that cost efficient nous to be able to say, alright, it actually is cheap enough to do this now and it's gonna start by people deciding to spend the money to do it and then eventually hopefully will be a lot more patients will have access to it.

But just like anything in life, you know, as technology develops, people that have money are going to be able to do this and then slowly it will trickle down the more people that order it that cost and demand. Well keep lowering the price for their genetic sequencing. And and so I think that's that's where we're headed in the future. Um But it's going to end up bringing up more questions because the more people that have sequencing we're gonna say well what about all these genetic changes? So we need a lot more research in terms of figuring out, as we said, just because we have sequence the human genome doesn't mean we understand all of it. But really at the beginning of the understanding and I think that's why it's such an exciting field and one to keep your eye on for in genetics because there's just so much that developed so quickly. So hopefully we see that you know, as well as affecting people and just being able to get more genetic testing and to have that information to help them with decision making and health care. Yeah, I'm looking forward to seeing how this develops as well I guess. Um one possible outcome which to me seems almost inevitable in the long term.

Although maybe that's too strong. And I'd be interested to hear your thoughts is that basically, you know, at least in developed countries, whenever a child is born, the whole genome is just sequenced and that information is stored somewhere hopefully securely and then can be used as a reference point for all sorts of medical conditions later in life? Obviously we're not at that point yet. But if it becomes cheap enough and accepted enough, I could see that happening. I mean do you think that that's likely, would that be a good thing? Is there too many privacy issues like what do you think? Yeah, I think it's interesting. I there's something called newborn screening where in the us all babies have newborn screening unless the parent opts out and that's quite a process. I've never heard of a parent opting out. Um So where through a heel prick test with the baby they're tested for certain conditions that if we diagnosed very early can change a baby's life possibly saved their life. So obviously this is important. So I've asked a lot of guests myself like do you see whole axum or whole genome sequencing replacing newborn screening? Like what if we just learned this when someone is just born And as you said have that follow then.

And I think there's a couple hurdles we have to get through with that. Some of which are what about these adult onset conditions? Like we both said we don't really want to know about a condition that we can't do anything about. Right So that that's our own personal choices. You know we can't make a decision for a baby. What if they don't want to know any of this? So I think we'd have to come up with a way to Be able to unlock information as that child gets older. So at first only no conditions that are going to affect them in childhood teenage hood and then once they turn 18 then they could learn about adult onset conditions. But the problem is like all right, who's going to hold this data. How are we going to make it secure? Who's gonna let them know about these new conditions and 18 years. You know, those those people that would call you with the results are not gonna be in that same job 18 years later and have that set up. So I think in in this ideal world theoretically it's really great and interesting. But there's a lot of issues we have to work out. But I think we will get there at some point. You know, it may not be for our generation, but you know, maybe a generation below us or the next one or something where we we have this for as like a standard in developed countries.

Yeah. One thing I just listened to an audiobook recently about the Bay Area rapist. I think it was called the Golden state killer. Sorry. Yeah, I think they're the same. But yeah. Anyway, so I listened to an audiobook about this which was written by a woman who was basically just investigated it as a hobby and she actually died tragically just a couple of years before he was actually caught using genetic technology. And what was interesting to me is that his um this might sound like a tangent, but linking this back in the original crimes committed during the 70s and 80s where gene technology just didn't really exist. But material was collected which then later was subject to genotyping which allows you to basically if you have another sample from that person match. So you can, you can tell with high probability who it is. But you need, the point is you need a sample from that person. Now they actually ended up catching him because they had they found a match and I think it was an ancestral DNA database from someone who was his distant relative and they were or something like that. And they were able to then build different family trees based on that and then using other records.

And gradually they were able to process of elimination to sort of reduce it to just him. And I think that that's just amazing that that was possible that decades after the fact that you can use genetic material to define someone. And again, and I guess that this is sort of the criminal investigative fantasy. It's like if we just had everyone's markers on file for the whole population, you could just solve so many crimes basically instantly. As long as there's any genetic material now, of course, then you have, well, what about the privacy concerns there? And part of me thinks, well look, if you just store the markers, there's very little you can actually do with that information other than use it to identify a person. And I know that you know, maybe that's too quick. But I guess the point is that not to give a definitive answer on this by any means. But I think that in in that in that case, in the criminal justice case similar to what we were talking about in the medical case, we haven't as a society fully realized or worked out how to deal with having this information and all of the potential upsides as well as downsides that it represents. And I'm interested to see where that's going to go in the future. So maybe if you want to close out on a few thoughts on that. Yeah, I think that's it's interesting because that brings up a lot of privacy of like when I have used direct consumer test, you know I spit it's my spit.

I have it's my D. N. A. So I'm consenting to send that off for the company to sequence that or you know genotype I guess. Um and then now my D. N. A. Is in the database and it's labeled as like it's I didn't use a pseudonym like maybe I should have. Um And it's funny because I brought this up at like christmas eve with like a bunch of my cousins right? And one of my cousins goes, well you didn't have consent to do that. That's my D. N. A. To write because we're biological cousins related and you know and he's a sarcastic funny guy but you know point right? So when I send my D. N. A. If my you know funny great cousin if he goes out and you know commits a crime. What if they could use my DNA to help figure out oh it was Kyra's cousin right? So you know golden state killer case right there. Um So I think that does bring up that it's like with all of this data we don't know exactly how it will be used. And when we send it off to a company, that person probably doesn't fully understand that company's privacy policy. Like the company I sent it to could end up selling that D.

N. A. To another company and now they have that information. Um So I think that's something where with genetics overall we're like okay where could this information go and how are we going to use it in the future? It developed so quickly. You know even looking at things like we used to say oh it's an anonymous sperm donor. That there's no such thing as an amenity genetics anymore. Those people that were told oh it's anonymous now are getting identified through these databases of like oh I'm your biological son, I'm your biological daughter or whatever. And they were like I never signed up for this. It was an anonymous donation. So I think that's something to keep in mind with all of this is like we don't fully understand where we're going with genetics and and everything that we can uncover from it. Which I think is mostly exciting but also a little bit scary. Yeah. Well I agree and I think it's one of the good reason to be educated about some of the science behind it. So we can make more informed decisions and voting decisions and health decisions and also just giving advice for other people. So it's been a pleasure. I've learned a lot and hopefully listeners have to.

So um thanks kira for joining us today. Great, thank you for having me James and for anyone that wants to check out my podcast. It's DNA today. So you can search that on any any podcast player. It will pop up for more information about today's episode visit D N. A podcast dot com where you can also stream all episodes of the show. We encourage your questions, comments, guest pitches and ideas. Send them all into info at D. N. A podcast dot com. Search DNA today on twitter, instagram youtube facebook so you can connect with us there and a favor. Please rate and review the podcast on apple Spotify or wherever you listen. This truly helps us climb the charts and allow more genetic nerds like yourself to find the show. DNA today is hosted and produced by myself. I mean our social media lead is korean Merlino. Our video lead is Amanda Andrea lee. Thanks for listening and join us next time to discover new advances in the world of genetics. We're all made of the same chemical

#179 Genetic Testing with Kira Dineen
#179 Genetic Testing with Kira Dineen
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