The Science of Everything Podcast - Special Episode: Genetic Testing

Episode Date: February 27, 2022

In this special episode I discuss genetic testing with Kira Dineen from DNA Today. We cover a range of topics including the process and science behind genetic testing, the types of genetic conditions that can be tested for, the difference between genotyping and gene sequencing, and the promises and potential issues with direct to consumer genetic testing. We also discuss developing social practises surrounding the use of gene technology, difficulties of informed concept, use of genetic material for criminal justice and ancestry databases, and potential future developments of these technologies.  Link to Kira's podcast: DNA Today (dnapodcast.com) If you enjoyed the podcast please consider supporting the show by making a PayPal donation or becoming a Patreon supporter. https://www.patreon.com/jamesfodor https://www.paypal.me/ScienceofEverything

Welcome to The Science 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, Kira, tell us a bit about yourself and your podcast and sort of what you do over there. Sure. So my name is Kira Deneen and I am a genetic counselor. 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 I'm pregnant in the near future 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. And it's, it's been a blast. I talk 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. 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. 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 and kind of get my feet wet with genetics and learned 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 and now being, you know, actually full time employer or employee in 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. And now sometimes I have an idea of what the guest might say depending on what we're talking about. But yeah, 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 and 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 or if there's a possibility that future children, biological children of theirs could have a condition. So really being able to look at risk levels or give it a diagnosis. So with genetic testing, we're looking directly at our DNA. So the code of life. And so we're looking at this code and saying, okay, is there anything that's different there? 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 and how, you know, inexpensive it is now. Yeah, it's pretty crazy how much that technology advanced and I want to talk a little bit more about that later. But I want to start with delving into some of the science a little bit more. So we've talked about genetics a few times on the Science of Everything podcast. 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 what your background is. So one thing that we know is that DNA consists of a series of nucleic acids. And we know that DNA codes for proteins, which are molecules that carry out many of the key functions in our body, and that differences 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 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 tests exactly. So are they doing a full genetic sequence? or are they just looking for particular markers? Like, tell us a bit about how that works. Yeah, so it definitely depends on what the healthcare 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, yeah, with like you get a kit 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 DNA in it. So I can have blood from a patient or saliva and I can do a lot of the same testing. Sometimes you need blood for a certain reason, but in general, for a lot of genetic testing, you can have either.

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 hotspots? it also 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. So this is, I mean, you imagine how much data that is.

That's a lot of data to sort through. But that would be like the biggest. It's about three billion nucleotized. Is that right? Paricle correct. Yeah. Yeah. So that's a lot of letters to read through, right?

And the next, you know, the tier below that would be whole exome 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 mRNA and then translated into protein. So these are the genes that are actually made into proteins and actually doing something in your body directly. So a lot of testing now is whole exome sequencing because we're like, well, let's just look at the active genes. Is there 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 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 no to go around to it. When they take a blood sample and if they do some genetic tests on that or using that for, so forensic genetics or whatever. Where do they actually get the DNA from? Because erythrocytes, red blood cells don't have DNA.

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 as I said, there's some exceptions that some of our cells don't have all of our DNA. And as you brought up, red blood cells don't. You know, 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 cool that you're able to basically separate out that blood cells. sample into red blood cells and white blood cells. So in the white blood cells, you're able to actually get DNA 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 cariotype. So that's a different type of genetic test where we're actually looking at chromosomes. So our DNA 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 and 23 from our biological mother.

So when I would do karyotypes and looking at someone's chromosomes, seeing if there was anything different there, you know, I would break apart and say, 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 chromosome.

Yeah. So the layers come from centrifugation. 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, 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 this works in practice. Okay, so that's, that's the blood tissue. Now about, about saliva samples. So what actual cells are in our saliva? I actually have no idea there. I assume saliva is mostly water, which obviously that's not going to 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. Yeah, yeah. 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 for each side. So that we're like trying to directly get cheek cells. 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. Because sometimes the test will come back and say, oh, there wasn't enough DNA in the sample. And I'm like, I feel like maybe that patient ate something in the waiting

room before. And they're like, no, no, it's fine. I've had nothing. Or I send them home with a kit and they have something. And they're like, oh, I'm sure it will be fine. But yeah, because some people ask me like, oh, is accuracy any different? I say, no, if we're able to get the DNA, 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'll just have a huge meal before this massive operation. It's like,

what are you doing? Like, why? Yeah, now we got to reschedule that. Everybody's got to wait at the hospital, whatever it is. Yeah. Yeah, definitely. It's strange. Anyway, okay, so that's, so we can get genetic materials through blood sample or through cheek swabs or saliva. And we sort of mix the material, get the cells we need and extract the DNA from that. So I have a question then about whole exome sequencing, because as you mentioned, basically all the cells in our body have the same DNA, for the 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 exome sequence, does that not depend on the type of cell that you're looking at? And is that important for any of these applications?

Yeah, that's a good question. So that is a whole other area of testing, so like epigenetic testing, looking at what genes are turned on and which are turned off. That's going to be very tissue dependent, cell dependent. When we're looking at whole exome sequencing, we're just looking at any genes in the genome, the human genome. So it doesn't matter if, okay, my eyes are going to have different genes turned on than my lips do because they look different, right? They have different pigments.

So for whole exome 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. And later we found out, all right, we're not going to 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. So it's more like regulatory roles or it's controlling other genes. So, you know, when we're looking at whole exome sequencing, we're just like, all right, let's look at the active genes. So it's not necessarily active to that tissue. Yeah. 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. Yes, exactly. And as well as epigenetics and control of gene expression. something that is, well, 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 tangent, 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 1% or so if the DNA actually codes for protein? And then some other percentages are involved in control of gene expression regulation, 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 virus,

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 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 a very, we don't really know, but I'm just sort of 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. Yeah, a little bit. Yeah. So basically what CRISPR is, is we discovered this naturally in bacteria, you know, a little over 10 years ago. Well, it was discovered before that, but, you know, a lot of developments 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 DNA 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. So I think that that's interesting when we look at like the evolutionary process and that, you know, even like our mitochondria, one of our organelles, our, you know, organelles are like little organs in our cells, you know, those used to be not there. That used to just be bacteria. And then at some point, you know, became in our cells very long time ago.

So I wonder from like an evolutionary standpoint as you're bringing up, like are some of what's in our non-coding DNA like is part of that like old, old viruses that we like fought a long time ago and are keeping track of that. Certainly not an area of expertise for me, but I'm kind of like you. I'm like, oh, that's an interesting area to like look at. And I wonder with CRISPR 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.

So what are all the roles to it? Yeah. I think that it's, 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 exactly 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 percent complete yes i know that was still not sure exactly where we are now yeah 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. Right. I think that's a lot of in like the telomere. So the ends of the chromosomes. Yeah.

Next question I have is sort of related to this that there's sort of two terms that, but 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 when I'm looking at like, which 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 going to see, is there any differences in that gene? Now, genotyping is we're just going to 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 going to actually drive through. We're just popping in on the exits, 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, which we also call pathogenic variance. That's more of the scientific term now for a mutation. So we used to say, all right, well, this is the most common mutations. Let's just look for that. let's not just let's not take the time of look through the entire gene. And there's advantages to that.

Obviously, it's going to 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 going to miss that because you're not even going to 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 just the point of clarification here, you're talking about sequencing an entire gene.

So 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 exome. 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 we were ordering a whole exome, then we're just going to be sequencing all of the active genes we talked about. Whole genome, everything.

We're going to sequence everything. And then, you know, I haven't ordered any of those. So 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 going to have my patient be sequenced for, for those certain genes. 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 they a carrier of a condition like cystic fibrosis, sickle cell? I want to sequence those genes. I'm not going to, I don't care about the rest because I'm in a prenatal setting. That could change in the future. But yeah, it definitely depends on like why you're ordering the test, what you're looking for. Yeah. So just 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 about? I think it's around like 20, 30,000. Yeah, that sounds right. I've seen, I've seen some different estimates. I recall that before the human genome project, people, scientists had estimated it was much higher like 100,000, but then it was discovered that they were actually far fewer than they'd expected,

which itself is interesting. How we sort of. We really thought highly of ourselves. 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, we're 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, oh, to do more things, you need more genes, but maybe it's actually just that you have more complex and intricate control of the regulation. Yeah.

I think you're on the right track there because otherwise we would have that correlation between like, all right, if an animal is more complex, then 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 all right so there's something that we're not quite understanding there and yeah it's probably lies in epigenetics there yeah um anyway so just coming back to what we were talking about before so yeah if there's about three billion nucleotides and and if you do a whole genome sequence then obviously that's a lot um a whole exome sequence but that's about one percent of that so that would be uh what's that uh 30 000 i think

sorry 30 million um and then um yes easy to get the orders of magnitude's wrong And then if we've got about 30,000 genes, so you pick a few of those and sequence those, a gene is, I don't know, a thousand, a few hundred long, depending on obviously it varies by the gene. 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 sort of been talking a bit 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 the some of the, what are some of the applications there in either of those? Yeah. So there's so many areas of healthcare where we're ordering genetic

testing. I can speak to my area first and then kind of fan out from there. So as a prenatal genetic counselor, I kind of mentioned before, all right, a panel of genes. So if I was doing carrier screening for are someone that's pregnant and their partner. For that, I'd be looking to see are they a carrier of the same condition? So these are autosomal recessive conditions for the most part. And I'm looking to see 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 they're for the most part healthy. They probably don't have symptoms from it. if both a patient and their partner 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 to a baby 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 a carrier for anything and,

you know, are the couple matching for a condition? So that's a case where we're not, nobody has a disease, nobody has a condition, but we're, you know, more doing it on the preventative side. So again, that's like more of the gene panel. Yeah, sorry, just to clarify with that. So the key, well, the way I think about it 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 the difference that we talk about between genotype, which is their genes and phenotype, which is the characteristics that they express. And so they may have no idea that they are 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 onto their child, then the child could exhibit the trait.

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 as you said, most people don't realize they're a carrier for a condition because most times carriers don't have any symptoms. So some people might say like, oh, well, I'm healthy. Like I don't see the point of doing carrier screening. They say, well, most people, if we look at enough conditions, most people are a care. for something because we're, you know, we're testing for hundreds of conditions. For only testing for a couple, all right, you're probably not a carrier for those.

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. I'm sorry, go ahead. You were then going to talk about other applications. Yeah. So another application that I order is for people that are pregnant. there's a test called non-invasive prenatal screening.

And this is really cool because we found out that coming off the placenta are cells that float in the pregnant person's bloodstream. And those cells tend to pop open and release the DNA. So by taking a blood sample, we can isolate that DNA and then screen for genetic conditions. And these are random conditions, not inherited like I had 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 has become much more popular. It was clinically available about 10 years ago, but the last few years has become much more popular. Yeah. So for these, so we've talked about 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 characteristics or disease states in the offspring. And so what you're saying is that there are, there are actually, 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, wouldn't 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, 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. But yeah, I'm also a little curious

because 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 and our genetic child. But what's interesting is that the cell-free DNA, so when a cell pops open and releases the DNA, that is after a person gives birth, that clears from their system very quickly. I've heard like hours like that quickly. But the cells that are still in 10. act, that can stay in a person's body for years. Oh, wow.

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 like amazed. It was talking about some case where they were able to find in people that they had for people that are 46XX. So like a traditional female chariotype that they were able to. define some Y cells, some cells that had the Y chromosome. And they're like, well, what is this? And they're finding it was the origin was those people's sons from previous pregnancies,

that their cells were still there. And I was like, that's still amazes me to this day. And I read this book like four years ago. That's crazy. I've never heard of that before. Yeah, isn't that wild? But the technology takes advantage of the cell free DNA. That's how it works. So if we were looking at cells that are intact, it wouldn't, it would fall through. We wouldn't be able to test it. Yeah. Oh, that's really interesting. Okay, so so far we've got testing for recessive conditions in parents and also testing

residual DNA from pregnancy. What other applications are there for a genetic 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 if our 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 BRCA 1 and 2. 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, she has a pathogenic variant in a BRCA gene and ended up having preventative surgery so that she was reducing her risk to develop cancer.

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's high risk. Let me see if I have 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 led to the cancer to happen?

So 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, as well as for genealogical tests, which are increasingly popular for people find out about their ancestry, and for paternity testing, which is obviously one people will be familiar with. 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 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, 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 would just mention that because listeners may also be thinking about that. Yeah, that's cool. 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 necessarily, or 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 a tricky area, partly because in many cases it's sort of not known whether or not there's any 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 variance slightly increases your risk of this type of cancer and so forth. And that sort of information is sort of quite abstract and often difficult for people to, well, it's often difficult 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 it themselves, but there's a healthcare 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, 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, I think it's, it's important to know that it's not going to be as extensive as testing you're going to get with a health care provider. So using the breast cancer genes that I was talking about before, BRCA 1 and 2, I think that's a good example because, you know, and I'll be frank,

a 23 in me does a test, well, test for these genes. And a lot of people know of this company is one of the biggest drug consumer companies. Yeah, they've received a lot of press coverage in the last days. Yeah, definitely. And so with the big, BRCA genes, they do genotyping like we talked about. So they look at the three most common mutations in BRCA genes. Now, these are mutations that are common in the Ascanaji 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 in that

DRCA 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 genes or a different gene related to breast, varying cancer, prostate cancer, all of that. So I think it's, there's a time and a place for it. You know, I think the ancestry is very interesting as well, but it's also something that 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 one of, you know, branches of my family is from Ireland. My testing gets so specific to say I'm from East Cork, Ireland. Oh, wow. 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 other thing, right?

But, you know, people have more recent African ancestry. It's probably going to 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. 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 in 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 so forth, it's not like one, and I think people don't understand this for a while. It's generally not the case that a particular variant is definitely going to give you a particular disease. Yes. There are some diseases like that, but for the most part, it doesn't work that way.

And it's an issue of, well, it increases the risk or possibly decreases risk by a certain amount. 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, I'm just making this example up, 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 layperson. 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 U.S., they've recommended that these be reported. ACMG. Yeah, ACMG in the U.S. at least. I'm less familiar with Australia, to be honest. Yeah, I don't know that the case is probably similar, but that they, Right. Just to give a bit of background there.

So there's a further complication here in terms of we've been talking about whether someone sticks out this genetic information. But there's a further issue that if a diagnostic test has been conducted for some other reason and they sequence 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 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 there's this list of around 60 particular variations that, as I, as I'm a lot of, I understand it's recommended. I don't know that they legal or 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, ACMG 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 exome sequencing that we talked about or 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 a health care provider and decided if something comes up in one of those genes, 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 BRCA gene mutation where, okay, they have an increased risk for breast cancer or ovarian cancer, prostate cancer.

So it's different cancer risk there. And so in those situations, people can have the option of doing more screening. So for breast cancer, they might be doing breast MRIs, ultrasounds, possibly mammograms, definitely, 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. All right, that's pretty high. Some people

decide to do the preventative surgery. So that's called a prophylactic bilateral mastectomy. So a bit of mouthful. I always have such long names. Very long names. It took me years, I have to say, to get all the lingo down and pronounce it right and everything. But so there's certainly for some conditions and some genes that we find in 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 high. 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 the 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 going to be true for a lot of people that

there's the question about increased worry and stress 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 a factor that's people, I think, overestimate the effect of genetics. I don't actually know if there's data on this, but. Yeah, I feel like it's true, though. And I think that that's something that the medical field is sort of trying to be more cognizant of is doing more about sort of encouraging positive lifestyle changes instead of just focusing on the genetics.

Obviously, though, that plays a role. And they can interact, as I, 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, I would say, have a perception that information is always good and that 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 the condition has a 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 all of these things have costs associated with them. So there's a balancing act there about how medically useful information is and what the risk is

balanced against the costs and the stress. And I guess I would add as well, just sort of attention taken away from things that might be more helpful, like lifestyle improvements. Right. Yes. Yeah, definitely. And I think another aspect of that is like looking at informed consent, like in our healthcare 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, consenting patients into doing this whole genome, whole exome, 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? And I think it is really important, like, 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 non-invasive prenatal screening. You know, I talk it through and I say, this is what we could find out? Patients would 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, I'm really about 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 science of everything before is different cognitive and 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 a disciplinary 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 mean, I guess broadly, the genetic age is only, well, I don't know, if you date it from the beginning of the, from the sequencing of the human genome by 20-ish years old, we're still sort of learning how to do an information-rich genetics age. And 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, we're groping around a bit and trying to work out how to do it well. Yeah, I think so. So before we finish up, 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 exome sequencing or whole genome sequencing because a lot of the testing is, okay, we'll do a gene handle. 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, all right, let's sequence their genome, let's sequence their axome. 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-efficientness to be able to say, all right, it actually is cheap enough to do this now. And it's going to start by people deciding to spend the money to do it. And then eventually, hopefully, we'll 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 will keep

lowering the price for their genetic sequencing. And so I think that's where we're headed in the future. But it's going to end up bringing up more questions because the more people that have sequencing, we're going to 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 sequenced 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 develops 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 in healthcare. Yeah, I'm looking forward to seeing how this develops as well. I guess 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. There's something called newborn screening where in the U.S. All babies have newborn screening unless a parent opts out, and that's quite a process. I've never heard of a parent opting out. So where through a heel prick test with the baby, they're tested for certain conditions that if we diagnose very early, can change a baby's life, possibly save their life.

So obviously this is important. So I've asked a lot of guests myself, like do you see whole exome or whole genome sequencing replacing newborn screening? Like what if we just learn this when someone is just born? And as you said, have that follow them. 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'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. teenagehood. 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 going to let them know about these new conditions in 18 years? You know, those people that would call you with results are not going to be in that same job 18 years later and have that set up. So I think in this ideal world, theoretically, it's really great and interesting, but there's a lot of issues we'd have to work out. but I think we'll 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 rehab have this for as like a standard in developed countries. Yeah, one thing, I just listened to an audio book recently about the Bay Area rapist, I think it's called. So it's a- The Golden State Killer. Oh, sorry, yeah.

I think they did the same. But yeah, anyway, so I listened to an audiobook about this, which was written by a woman who was basically just an event. 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 this might sound like a tangent, but I'm linking this back in. The original crimes were 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

tell with high probability who it is. But the point is you need a sample from that person. Now, they actually ended up catching him because they had it they found a match in i think it was an ancestral uh DNA database from someone who was his distant relative and they were able to think a distant cousin or something like that yeah and they were able to then build um 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 um to find someone right and again and i guess that this is sort of the um the criminal investigation

get a fantasy. It's like if we just had everyone's markers on file, like 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 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 sort of 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 tests, you know, I spit. It's my spit. I have, it's my DNA. So I'm consenting to send that off for the company to sequence that or, you know, genotype, I guess. And then now my DNA is in the database. And it's labeled as cured dene.

Like it's, I didn't use a pseudonym like maybe I should have. 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 DNA too, right? Because we're biological cousins related. And, you know, and he's. He's a sarcastic, funny guy, but, you know, point, right?

So when I send my DNA, 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 Keir's cousin, right? Well, they can. They've done it before. So, you know, Golden State Killer case right there. 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 DNA to another company. And now they have that information. 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 develops so quickly, you know, even looking at things like we used to say, oh, it's an anonymous sperm donor. There's no such thing as an anonymity in genetics anymore.

Those people that were told, oh, it's anonymous now are getting identified through. these databases of like, oh, I'm, I'm your biological son. I'm your biological daughter, 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 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 reasons 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 the people.

So it's been a pleasure. I've learned a lot and hopefully listeners have too. So 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 podcast player, it will pop up. Cool. Thanks everyone for listening. I hope you enjoy the show. And I'll talk to you next time.