#177 Whole Genome Sequencing with PerkinElmer Genomics
World-renowned medical geneticist Dr. Madhuri Hegde, joins the show to explore whole genome sequencing (WGS). She is the Senior Vice President and Chief Scientific Officer of Global Lab Services at PerkinElmer, a global leader in genetic and genomic testing focused on rare diseases, inherited disorders, newborn screening, and hereditary cancer.
Dr. Hegde is also a board certified diplomate in clinical molecular genetics by the American Board of Medical Genetics, and an ACMG Fellow. Previously, she was the Executive Director of Emory Genetics Laboratory. She received a B.Sc. and M.Sc. from the University of Bombay and a Ph.D. from the University of Auckland. She completed postdoctoral studies at Baylor College of Medicine.
On This Episode We Discuss:
The difference between WES and WGS
How WGS differs between laboratories
The frequency at which WGS reveals an additional condition/disorder that the ordering providers were not expecting
Situations in which trio testing is helpful for WGS
Prenatal WGS
The future of newborn screening
WGS for hereditary cancer syndromes
How people learn more about PerkinElmer’s WGS
Learn more about WGS at PerkinElmerGenomics.com and follow them on Twitter, Facebook, and LinkedIn. Be sure to follow our guest, Dr. Madhuri Hegde, on LinkedIn.
Head over to our social media to enter our giveaway! Search “DNA Today” on Instagram and Twitter. Go to our host’s posts on LinkedIn by searching “Kira Dineen”. There you can enter to win “Modern Clinical Molecular Techniques”. Dr. Hedge is one of the editors. An earlier edition was one of Kira’s textbooks in undergrad!
Stay tuned for the next new episode of DNA Today on April 1st 2022, where we’ll be discussing single-cell spatial genomics with Vizgen! New episodes are released on Fridays. In the meantime, you can binge over 175 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel.
DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli.
See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com.
Curious to take a peek inside your body's drug response? Then you should check out Picture Genetics’ PGx Test. Powered by clinical laboratory Fulgent Genetics, Picture’s PGx Test is easy to order and understand, with hassle-free clinician involvement and good looking reports! Plus you are fully supported through live chats, emails and genetic counseling. To order your Picture PGx test kit, visit picturegenetics.com and use code “DNATODAY” for 25% off and free-shipping! Get actionable genetic insights today to benefit your health tomorrow. Check out Picture Genetics’ interview about pharmacogenomics with their Director of Genetic Counseling, Gregory Kellogg on Episode #174 of DNA Today!
Have you heard of the Blueprint Genetics My Retina Tracker Program? This program offers eligible patients in the US no-cost comprehensive genetic testing and counseling for their inherited retinal degeneration. The My Retina Tracker Program Panel includes 351 genes, mitochondrial DNA, and non-coding variant assessment. Stay tuned for our interview with Blueprint Genetics about the My Retina Tracker Program and the patient registry on a future episode of “DNA Today”. In the meantime, you can learn more at BlueprintGenetics.com.
Polygenic risk scores (or PRS) are a powerful way to identify an individual’s risk of common disease by analyzing up to millions of genetic variants spread across the genome. Allelica has launched the first PRS test on the market to calculate ancestry-specific PRS for breast cancer, prostate cancer, coronary artery diseases, Type 2 Diabetes and Alzheimer’s disease and deliver the results in a clinical-grade report. Order your test today at order.allelica.com. For 25% off AND free shipping, use code “DNATODAY” at checkout. Allelica: Empowering the next generation of clinical genomics. Check out Allelica’ interview about PRS with co-Founder and CEO Giordano Bottà on Episode #168 of “DNA Today”!
Transcript
Please note that the transcription was automatically generated and may contain errors.
Kira(host): 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 Kira Dineen. I'm a certified genetic counselor and your host. Joining me now is world renowned geneticist Dr. Madhuri Hegde. She is the senior vice president and chief scientific officer of global lab services at PerkinElmer.
Madhuri(guest):Thank you for having me,Kira.
Kira(guest): So why don't we start by just explaining some of the basics and explaining the difference between whole exome sequencing and whole genome sequencing. Before I have all of my questions about whole genome sequencing.
Madhuri(guest):I think that's a great way to start. So ,when we are talking of the genome we're talking of all the genes that we know today, around 22,000 genes. The sequences within the genes which are not making the proteins and the sequences between the genes as well. So we are talking of intra genic ,inter genic sequences and the coding regions of the genes. So essentially that makes up the genome. When you're talking of the eome, we're really taking out that tiny piece of the genome about the coding regions of the genome which is about 1-2% of the entire genome.
Kira(host): So it's such a small slice of that pie. When you think about 12% that's that's so tiny and we used to say the rest of it is junk DNA which is a term we don't use anymore because we know they're there are changes in the rest of the genome it certainly can have effect on our genes and and how our body reads our genes and processes them. When is it important in the clinic to order a whole genome sequence? Does it ever make sense to just jump right to a whole genome sequence and bypass som and genome panels or gene panels?
Madhuri(guest):I mean I think that's a great question I think for to answer that question we really have to see what has happened in the last 10 years. When I started in genetics we were doing Sanger sequencing and we were doing single genes.Most of the testing in clinics is order based on the clinical presentation. That's one thing. The second thing is at least within the U. S, there's a lot of dependency on whether a test is going to get paid or not. So that's one side of it. The other side of it is technology. The technology has gone so fast and so quickly that today we can do the whole genome in a very affordable price in our cost rather in a clinical lab. So the question is very valid but the the answer is little two pronged here in the sense that it depends on the laboratory, the laboratory setting, the affordability of the test itself and can it be done in that particular setting.And we're talking I'm talking global labs here because I run global labs and I can understand the constraints different labs face. Now if you just look at the technology, I would say go straight to whole genome sequencing ideally largely because you're sequencing the entire genome, you're getting all the coding regions are intra genic and the inter genic sequences. Your diagnostic yield is going to be higher compared to the exome. But having said that, I would still say that exome sequencing is probably the right way to start based on the cause, the reimbursement and the laboratory setups that are currently out there. There are not that many labs which are able to do clinical whole genome sequencing.
Kira(host):So we'll get there. But for now I think as you're saying, most of the time you're starting with exome then depending on the clinical presentation, insurance coverage where you are in the world and all of that but you see that gene panels are not being ordered as much anymore because like like whole exome is replacing gene panels in some settings.
Madhuri(guest): That is true. So it's a very interesting situation in the clinical setting in a clinic and a genetics clinics or a pediatrics clinic where there's an unexplained conditions suspected and could be genetic, they're going to exome and genome and gene panels are not really that highly ordered. But if you just now flip that there, you know, we've got so many therapeutics coming up and large pharma and small pharma are getting interested in genetics and specific genes. They are not running exams and genomes. They want to do a panel because they have specific genes they want to look for and they will contain it to doing small gene panels based on what they're looking for and
Kira(host): when ordering a wholeexome sequencing and providers are looking at lots of different labs that provide this. Is there a difference between labs or is it just a very standard test that it doesn't matter where you get it from.
Madhur(guest)i:So that's a great question. And it's a very important one too. I most of my talks, I always say this their genetic counselors who are really in the midst of in the middle between the patient and the lab actually deciding the test order and where to go. I think there are very important questions the physician and the genetic counselor need to ask the laboratory first thing is the matter use how many how are the jeans covered our genes? There's deep coverage of the genes.
Kira(host): So how many times a gene is actually read. You don't want it just once you want it many times
Madhuri: And you will see there is a difference. Some labs do 70 x a standard is 100 x. Then what is the design of the exam itself is absolutely critical and the reason I say that I'm going to give you a very simple example. Okay. Duchenne muscular dystrophy. Majority of the events are deletions and duplications. About 70% and 30% are single nucleotide variations.Out of the 30%, about 5-6% are deep in chronic changes, their deep into the entrance. Duchin introns are very big, 50 kb introns. So unless your design is done in such a way that you're tagging that particular single nucleotide, then you're not going to pick it up otherwise because you're not put a bait there. So depth and how the design was done is absolutely critical to look at when ordering exam, sequencing or any gene panel
because you don't you want to avoid a patient having, oh this patients negative for D. M. D. And now we've missed this diagnosis and the whole diagnostic odyssey is going to really be affected from that. So you don't want to miss diagnose.
Madhuri: Absolutely. And you know, it's very difficult to order the same tests again, especially when you are depending on insurance to pay for it.
Kira(host): I know you already did that. I'm not paying for that again. And then they don't understand all of these details is you know, a lot of people in healthcare don't even understand these details that are that are ordering this?
As you said like this is what health care providers, genetic counselors need to be asking to know like okay, well which lab am I going with, What is it actually gonna tell me and what can the test not tell me? Like both sides of it.
Madhuri(guest): And I think the genetic counselors play a very big role in this. Nowadays. The training of the genetic counselors includes all this information. They are very much up to date with all the conferences they are attending and they play a big role. They understand this well and they're ordering the test in interest of the patient and this is very important for that reason.
Kira(host):Yeah, as a genetic counselor it's up to me of what lab I'm choosing, you know, for my patients and so you know the patients aren't deciding that you know, very rarely am I in that situation where I say to patients we could do this or that. But um another thing that I've always wondered with whole genome sequencing is does it ever include mitochondrial D. N. A. Because that's not technically part of the genome from the nucleus, it's it's kind of its own genome in a sense. Is that always included? Sometimes? Never.
Madhuri(guest):So when you're doing exam sequencing you have to make sure you put the baits for the genome for the mitochondrial genome just to be correct when you're doing whole genome sequencing your sequencing the autism and mitochondrial genome as well.
So you don't have to do anything special for that in the whole genome. The beauty of doing whole genome over whole eggs. Um Especially if you want to look at the mitochondrial genome is the depth of sequencing you get when you do the whole genome and the mitochondrial sequence you can get 1000 X depth and that's the data is absolutely amazing to look at.
Kira:So you said before depth like some labs maybe do 70 but you said 100 is like a standard like that. That should be 100. But you're saying it could be up to 1000
for the mitochondrial genome.
Okay that makes sense because for the mitochondria your there's only so many genes there it's not as large as the nucleus black compared to the genome of the nucleus. Yeah.
Have you heard of the blueprint genetics? My retina tracker program. This program offers eligible patients in the US no cost comprehensive genetic testing and counseling for their inherited retinal degeneration. My retina tracker program panel includes 351 genes, mitochondrial DNA and non coding variant assessment.Stay tuned for an interview with blueprint genetics about the my retina tracker program and the patient registry on a future episode of DNA. Today. In the meantime you can learn more at blueprint genetics dot com again that's blueprint genetics dot com.
Did you know 90% of people carry at least one drug reactive gene variant. Yes it's actually that common. That's why picture genetics. PG. X. Test is so helpful. The at home test kit helps you personalize your medication planning based on your specific genetics. The test is powered by full gen genetics, a clinical laboratory that uses pharmacogenetics to analyze your genes. To help you identify what meds work best for you. No more blind guesses. PG X testing gives you genetic insight on your body's ability to process different drugs. Tests come with a clinical report and genetic counseling. So you're fully supported and educated about how the results could impact. You. Use the power of genetics to find the right medications with picture genetics. P. G. X. Test visit picture genetics dot com and use code DNA today for 25% off and free shipping again. That's picture genetics dot com With code DNA today for your picture PG X test kit.
Get actual genetic insights today to benefit your health of tomorrow. Oh and check out picture genetics. Interview about pharmacogenomics with their director of genetic counseling. Gregory Kellogg on episode 1 74 of DNA. Today.
A polygenic risk scores or PRS are a powerful way to identify an individual's risk of common disease. By analyzing up to millions of genetic variants spread across the genome. Silica 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 great report. Order your test today at order dot ca dot com for 25% off and free shipping. Use code DNA. Today at checkout again, that's order dot A L L E L I c a dot com silica empowering the next generation of clinical genomics.
When we're looking at ordering whole genome sequence, saying, how often does it happen where whole genome sequencing reveals an additional condition or disorder that the ordering provider wasn't expecting?That's not the reason they ordered the test. So like an incidental finding. Um so they ordered it because you know, if we're going with our D. M. D. Example. Um So we're looking at that but we find out, oh actually there's you know a hereditary cancer syndrome. We're identifying, how often does that come up because you're looking at the entire genome and that's a lot of information. Exactly. So in our hands and we started doing whole genome sequencing in 2017. So we were one of the first laps to offer whole genome sequencing on a clinical basis. You were the first lab, Right? Yes. I was like, don't give yourself a little more credit than that. Yeah. Thank you. Yes, that's correct. And we have seen I have categorized into several categories. One thing is I'm just going to go through it, right, Dual diagnosis. About 5-10% of the times we have found more than one gene involved. There's another category I called the blended diagnosis where we see two different conditions looking as one condition.
But we find different reasons for it, then there is another category which we have recently started using this terminology as a camouflage where it looks like something but it is something completely different. And we find this quite often nowadays, you know, because you're right. We're looking at the whole genome. We're tagging deep in chronic mutations, inter genic changes. We can look at copy number changes, we can look at repeat disorders and say maybe there's a whole lot of information you're gathering from it. So we have we are in the process of putting our data together to publish it. Wow. That's exciting because I imagine you have so much data in terms of, you know, when people order like those three types of incidental findings that you could have from it. Um, and really changing a patient's care, I imagine because as you said, like, oh, it's actually two disorders. But we thought it was one or there's an extra disorder we didn't even have on the radar, you know, all of these different situations where I'm sure many of those cases patient care is changed because of it.
Yes, absolutely. And one of the things which I have sort of seeing the difference from doing whole genome because we are getting samples from all over the world just given the global footprint of our labs. We get a lot of samples from the Middle East, A lot of samples from India in Malaysia. And what we're doing is we're building up that variant data bank if you can say that and that really empowers us to interpret better, you know, people from all over the world live in the US and many times we find variants which are not represented in the caucasian population. So having that database at hand really helps us get closer to the diagnosis and that's so important. I brought that up multiple times on this show that um when we have genetic testing that often times if a variant comes up, if someone is of european background, they're much more likely to be able to figure out. Okay, what does this very mean? Is that just human diversity doesn't affect anything health wise or oh this is actually causing the condition that we're trying to look at.
Um so it's fantastic that Perkinelmer is really playing a role in ramping up that database so that we don't have the disparity as much for people of non european descent because this is such a big problem. When we started in doing genetic data and looking at this, we started with people of european descent and we're not including people of all different backgrounds and there's just a major problem there, You're absolutely right. I mean I've got so many examples now, especially from newborn screening where in the US we have picked up some variants in indian population or the chinese population and we have been able to talk back to our labs in India and china where that variant is probably a common variant for a particular disorder. And one particular case comes to my mind is P. K. U. Which is one of the most commonly that's how newborn screening started. Exactly exactly. Yeah. What 1960s somewhere in there like decades ago. And you guys have been doing newborn screening since 1994.
You've had 7.5 million newborn screen since then. Um so that's like 26-27 years something around there. Um so you're really a global leader in this newborn screening as you said looking at people from all over the world. How do you see newborn screening changing in the future? I mean as we said we've been doing it since the 60s in different ways. It's really changed over the years. But how do you see that changing in the future? Do you think whole genome is going to get incorporated at some point or like you know it probably depends on the cost. That's probably the biggest factor. The way I look at it is I think there's going to be an intermediate step and that intermediate step is probably going to be a gene panel. And the reason I say that is you can control the cost significantly today if you look at some of the techniques and methodologies that are available for doing hybridization and bait selection of genes. The pricing has come down quite significantly.
So there is right now a discussion going on about newborn screening, modernization and I think the question is going to be whether it's going to be molecular first or biochem first obviously Molecular first will heavily depend on our ability to interpret data the variants of unknown significance. We don't want to send families on a trip of you know, something that is not even real to build up that database before we do it as you've been talking about. Yeah. So I think it's gonna change then it is going to change is time and cost is gonna decide it. But gene panel of the rust jeans, let's just take for that as an example is definitely on the horizon fully. That will find even more babies that have these conditions so that we can do treatment immediately. And that really changes that look of a baby's life. That's the reason we do newborn screening. Yeah, I mean pompeii is a great example right, neonatal pompeii and adult onset pompeii. We know the whole spectrum of pompeii. What if we can pick it up so early that you know the symptomatic event never really happened, especially for those very well known disorders.
Like you said like pompeii, we we understand this condition as opposed to some other conditions where we say, well we still need a lot more research to understand that spectrum as a lot of genetic conditions are at that point, curious to take a peek inside your bodies drug response. Then you should check out picture genetics PG X. Test powered by clinical laboratory. Full gen genetics pictures PG X. Test is easy to order and understand with hassle, free clinician involvement and good looking reports. Plus you're fully supported through live chats, emails and genetic counseling. To order your picture. P. G. X. Test kit. Use code DNA today for 25% off and free shipping. Get actual genetic insights today to benefit your health of tomorrow. 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, 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 Clia 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. Did you know that genetic testing can pinpoint the cause of inherited retinal disease? In about 60-70% of cases identifying the disease causing gene mutation can help individuals qualify for a clinical trial for an emerging therapy, many of which now are gene or mutation specific. The my retina tracker program offers no cost comprehensive genetic testing and counseling eligible patients in the US for inherited retinal degeneration.
The my retina tracker is designed for people with a clinical suspicion or a diagnosis of a retinal dystrophy blueprints. My retina tracker program panel includes 351 genes and assessment of non coding variants. The panel has excellent coverage of the R P G R. O. R. F. 15 region which is critical in retinitis pigmentosa diagnoses. And here's a bonus. The panel includes the maternally inherited mitochondrial genome. Stay tuned for our interview with blueprint genetics about the my retina tracker program and the patient registry being established on a future episode of DNA. Today. In the meantime you can learn more at blueprint genetics dot com again that's blueprint genetics dot com. Another area that I kind of wanted to dive into a little bit. We've been talking about whole genome sequencing. Like in the clinical setting, we've been talking about it in terms of newborn screening. Um but what about in terms of hereditary cancer? Um So for hereditary cancer syndromes, those as I've seen, you know when I was a student in cancer doing genetic counseling, usually that's ordered with a panel of genes that are known to play a role in the development of cancer.
Um Now why could it be advantageous for someone with a potential hereditary cancer syndrome to pursue whole genome sequencing? Like how could this offer more insight than just the cancer gene panels? So I think we should remember that cancer gene panels and any gene panel for that matter is very evidence based right. You're looking at a bunch of genes where the evidence is pretty well established. We all know that especially councilors who have worked in cancer genetics clinics, there are many patients who come in who have got a family history of cancer and you really cannot pinpoint a gene on them. And in many times we can't even find the gene. I think that's where whole genome sequencing can play a big role. That the step up from a panel should be straight to a whole genome by skipping the whole exam in the middle because there's no point in doing the exam at that point. And you know this goes back to the very first question you asked me whether you do an exam or a panel If you do a panel in the clinic and that is negative straight go to the genome.
Yes. You always have to reflex to the next testing because if you didn't get an answer you gotta keep looking. Yeah that's interesting because I would think if we start doing whole genome sequencing as a reflex in these hereditary cancer families um that we're going to start identifying more genes to then be adding to the cancer panels as well. So it kind of works um backwards almost to that. It helps people in the future of you know these cancer panels have really grown. It used to be years ago you know for hereditary breast and ovarian cancer. We'd only screen for B. R. C. A. One and two. Now it's so much more than that. I'm always you know telling patients oh if you're someone in your family had testing years ago and you're saying it was negative maybe it was just those two genes. Maybe that should be revisited. And the way I know that my mantra one of my mantras is that the genome informs the panels. Also the genome informs the multi atomic strategies because one of the things that is going to come very quickly into clinical labs is functional analysis and multi atomic strategy is to figure out exactly what is going on with some of the variants which we just don't know what to do with them.
Remember our diagnostic yield is still sitting somewhere and as an average of Exum's genome around 30 to 40%. And that is the next leap. We need to take into RNA sequencing Protium sequencing and functional genomics that it interests me the RNA sequencing. How does that help us understand these variants? If we have a variant of unknown significance we say we don't know if this is causing the d not to work or it's just fine. It's just doing its thing there. Um how does RNA sequencing help us understand that difference and understand that variant basically when you're doing RNA sequencing you're looking at the direct impact of that variation on the gene transcript and then there by the protein itself. So there are two. Just two quick ways to explain it. One is a variant of unknown significance. It could have a variety of effects. One is a splice side effect that it creates a new splice side by which the gene is truncate.
The transcript is truncating earlier than its usual length. There are some of the defects which is still difficult to detect. Such as you know if the variant is causing a kink in the protein which we still cannot see doing RNA sequencing but are any sequencing is probably the first step. So my own researches in neuro muscular disorders and specifically despair apathy where we have found deep in tronic changes. We have one compound hetero cycles where one pathogenic and one variant of uncertain significance. We have been able to show that it causes a supply side effect. So the variety of ways to apply it in the clinic itself that case by case like can you do RNA sequencing for a variant for a particular person or is it more in that research side of? Oh now we know this variants. Now we can update clinical guidelines in terms of like what the labs are calling a variant or you know pathogenic variant versus benign variant. So right now it is case by case you do your usual panel exam a genome.
If the variant really fits the clinical phenotype, you can look at RNA sequencing one of the drawbacks of RNA sequencing, which we have to all remember is that the gene expression matters. So for example, Duchenne does not have a transcript in blood. You have to do that. Any sequencing on a muscle biopsy. So you have to have a valid reason to go and do such an invasive technique, right? Yeah. Most people don't want to sign up for a muscle biopsy. Exactly. And now, I mean you have to really say that this is really necessary to prove the clinical diagnosis. So it depends how many people have said that, you know, our NsC can eventually become the first year but it really depends on the gene expression which tissue is a gene expression. You really can't do it for intellectual disability because you can't get a brain biopsy. So that's not going to. So if it's available in the blood, it's easy, relatively. So another way that we can look at figuring out variants is like, you know, I think about in the pediatric setting of doing trio testing where we test the child with the condition or where we're trying to figure out what's going on with that diagnostic odyssey.
And we say, well, let's look at both of their parents biology and say, okay, if we find that parents have these variants and the parents, parents don't have those symptoms, then we can say, well, it's probably not what's causing it. That helps us have information. Um, Are there cases where we're also looking if that child has a full biological sibling? Do we ever do like more than trio where we're doing four genomes to look at? Like if their sibling either is asymptomatic or if they're symptomatic? Yes, I will tell you nowadays, we get a lot of quads and more than that in our lab. Sometimes entire families analysis is not trivial. But the one good thing about doing cards and more than that is most of these cases are cases where they have done a panel on the pro band and identified several variants of uncertain significance. And I give the credit to the genetic counselor in the physician that they from there, the single pro band panel, they went straight to a genome and did a quad or remote, they followed your advice going from panel to genome.
And that's when you can rule out most of the variants of uncertain significance. So it definitely is a step up and helps. But it's also important to do the quad analysis individually. Also what they mean is that the sibling against their parents and the program with the sibling and the parents and then take the sibling out and do the reassembly because you know, there's going to be a 50 50 chance here. So that analysis is involved but very important. It's just interesting how we can do this in so many different ways of like how can we figure out these variants. And I think it's exciting from you know, research standpoint and just how far we've come with genetics is you know, we say a lot on this show that, you know, the technology moves faster than the clinical guidelines and insurance companies and all that can keep up with, which is exciting but also frustrating when you're when you're working with patients. I wish we had more time because you're such a wealth of knowledge with this. I'm just asking all the questions that I've had about the whole genome sequencing here. I work in the prenatal setting. So I'm meeting with patients that are pregnant or looking to become pregnant in the near future is whole genome sequencing being done on amniocentesis chorionic villus sampling products of conception.
So either invasive testing during pregnancy or if someone has terminated or have a miscarriage is is this you know, being done either during pregnancy or after. We have just launched just this past month that we went live with. Obviously it has to be driven by an ultrasound or some finding that drives exomars genome sequencing. So we did do a study with an investigator at thomas, jefferson University for fetal high drops. And that was a very high yield study. The data is just published in genetics and medicine. Great. We'll put that link in the show notes for everybody. And it's also it's definitely moving in that direction. So for this so that we have to see something on ultrasound that we haven't figured out through carrier screening. Um Is this a situation where you'd say, you know, a standard um set of tests to order for an amnio or CVS is looking at doing fish um cara type micro array, um A. F. P. Which is a little bit separate.
But um would you say start with that and if all that comes back negative then reflex the whole genome or would you say start with that? If ultrasound findings are like just you know, can't figure it out. I would say straight go to the genome because remember genome is going to pick up copy number variation. So everything you're trying to detect by fish, you're gonna get identified. The only thing probably is a balanced translocation that's the exception. And I've been pushing so hard it's really a bioinformatics exercise to get to that. But if that is not something that is your primary suspicion I would straight go to the genome and during pregnancy everything is so timely. Um so you know it's it's important that you know I figured you were gonna say that but you don't want to be ordering tests three weeks later you get those results and then you're like oh let me order a whole genome. Like you don't really have time to play with during pregnancy. Exactly. And if you have had an I. P. T. Done and that's ruled out as negative and there's ultrasound finding I think it's best to go to the genome makes sense.
Yeah. Especially if the N. I. P. T. Noninvasive prenatal screening testing. If that has come back that it's looked at all the chromosomes. So there's some labs that offer it looks at expanded an employee analysis. So it's looking at not just the common 13 18 21 sex chromosomes but looking at you know any major missing or extra pieces of chromosome. Which I think is is helpful because I've had that come up a couple times of a trace of the seven a trace of me nine. Something that normally wouldn't have been picked up. But we're like okay this is this is making more sense. I mean we just picked up a U. P. D. Just yesterday in the lab and that is an advantage of whole genome right? You're just getting everything done at the same time instead of having to and as you mentioned time is so critical here in the pregnancy. Yeah certainly is. Thank you so much for coming on the show and just sharing your wealth of knowledge. I mean you're world renowned geneticist so it it really is just such an honor to have you on the show. And you know I was looking up in in the text book that you wrote a chapter of your your one of the editors um modern clinical molecular techniques.
I was like this looks familiar and it was one of my textbooks and undergrad. So um and lucky listeners um you can enter a giveaway for this textbook, you can search DNA today on instagram and twitter, you can also search my name on linkedin hired nine and you can enter our giveaway on there to win a textbook. And I believe I was checking out uh amazon, I think it's around like $200. So this is like you know and it's a staple textbook. I feel like anybody that has you know have any kind of lab background in genetics. Um like myself this is just like every, I feel like everybody has one, you know I'm sure I have a copy of it up here at my desk but um thank you again for coming on the show and for people that want to learn more, they can head over to perkinelmer genomics dot com. Um You know as we've been talking about you guys just launched the prenatal whole genome sequencing and you guys are global provider for just so much in genetics. Um so just very excited to have you guys as a sponsor on the show um and to be providing so much education.
So thank you so much. Thank you. Thank you for having me, kira for more information about today's episode visit DNA 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 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
