Scientists Scour Genome for Clues About Disease The reason some of us get diseases such as cancer or diabetes while others don't may lie in our DNA. Guests discuss the genetics of common diseases, including a new study that links variations in DNA to differences in how well different people fight HIV infection.
NPR logo

Scientists Scour Genome for Clues About Disease

  • Download
  • <iframe src="" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">
  • Transcript
Scientists Scour Genome for Clues About Disease

Scientists Scour Genome for Clues About Disease

  • Download
  • <iframe src="" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">
  • Transcript

JOE PALCA, host:

This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News. I'm Joe Palca. Ira Flatow is away. Coming up, we'll talk to a computer scientist who solved checkers. But first, a look at the genetics of disease. Just this week, new research links slight variations in people's DNA to possibility that they'll get diabetes, restless legs syndrome, or a rampant HIV infection.

These new studies are something called genome-wide association studies. Scientists aren't looking for a particular gene, but for variations in nucleotides. You know, those are the single letters and the three billion letters of DNA that make up your genome. These variations are called SNPs, single nucleotide polymorphisms. And scientists are finding that some SNPs match up with diseases like cancer, diabetes and heart disease. Sometimes, SNPs are located in genes, but not always, raising interesting questions about the function of the DNA between genes. These newly discovered associations also makes scientists wonder whether we should keep better track of our SNPs, so that we know if we're more likely to get a disease.

The Jackson Laboratory in Bar Harbor, Maine is addressing some of the questions posed by this new research at their 48th Annual Short Course on Medical and Experimental Mammalian Genetics. And joining me from the Jackson Lab in Bar Harbor is David Valle, he is the director of the McKusick-Nathans Institute of Genetic Medicine and professor of pediatrics, ophthalmology, and molecular biology and genetics, at Johns Hopkins University School of Medicine. David, welcome to the show.

Dr. DAVID VALLE (Director, McKusick-Nathans Institute of Genetic Medicine; Professor, Johns Hopkins University School of Medicine): Thank you, Joe. Welcome.

PALCA: Boy, that's a lot of departments to have appointments in. Well, we'll talk about that. And also joining us from Bar Harbor is Lawrence Brody, he's a senior investigator at the National Human Genome Research Institute. Welcome.

Dr. LAWRENCE BRODY (Senior Investigator, National Human Genome Research Institute): Hi, Joe.

PALCA: And also, Aravinda Chakravarti, he's the director of the Center for Complex Disease Genomics at the McKusick-Nathans Institute of Genetic Medicine, and professor of medicine, pediatrics, molecular biology and genetics at Johns Hopkins University School of Medicine.

So we hope you'll join us this hour as we talk about these really remarkable new tools that have been brought to bear on genetics, and in truth, how the whole world of what we used to talk about in terms of the genetics of disease is shifting. So give us a call. Our number is 800-989-8255, that's 1-800-989-TALK. And if you want more information about what we'll be talking about this hour, go to our Web site at, where you'll find links to our topic.

So, Aravinda, maybe I could start with you. I mean, I don't want to get too technical here, but what are these new studies about? Why is it important to look at these SNPs?

Dr. ARAVINDA CHAKRAVARTI (Director, Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine): Well, we've known for quite a long time that genetic factors are important in probably each and every disease, and all of the evidence for this has existed for some time. The evidence has often been quite indirect.

And we really come into a confluence of a number of, you know, different advancements. As many of your listeners would know, 2003 was the culmination of - the completion of the human genome and, in some sense, one phase of the Human Genome Project. Two years ago, many investigators around the world, including ourselves, participated in a map of genetic variations, the SNPs that you talked about. And the current stage is that we have over four million such identified positions in the DNA sequence, specific letters of the alphabet, that are different between different individuals. We know where they are, we don't know exactly what they all do, but at least we have a good accounting of their frequencies in different populations.

The third thing that's really happened because of this is that many groups around the world, and clearly in the U.S., that we have assembled fairly large cohorts of patients and appropriate control for these individuals who are free from disease. And so what we can now do is, based on these findings of genetic variations in the human sequence and by comparing these SNPs in very novel kinds of assays and technologies that could look at literally half a million such sites of the genome at any one time, in a large collections of patients and controls, that we can sift through the genomes, if you will, and identify specific sites that mark the genomes of those who have the particular illness. And in fact, these sites are quite different in frequency than those that have not.

So what that allows to do, in some sense, you know, very much like panning for gold, is in one box, we can identify a collection of SNPs that give a profile of what the disease may look like, and in fact that profile is distinguished from the profile of those that are free from disease. So SNPs have been tremendously useful and the technologies for looking at them are now sufficiently robust that we can do these studies in a compelling way. And once we have a finding, we have sufficient numbers of additional patients where we can replicate that finding and be sure that the finding is correct. And this summer has been really...

PALCA: Well, it's...

Dr. CHAKRAVARTI: Go ahead.

PALCA: Oh, no, I'm just saying it's been stunning. There has been one or more studies a week. It's really been remarkable. Larry Brody, I just - before we get to you, I want to remind people that they're welcome to call with their questions at 800-989-8255, that's 800-989-TALK. And Larry Brody, if I can turn to you for a second, I mean, you've worked in the genetics of breast cancer. How is this study of SNPs, these whole genome association studies, going to add to what we know about the genetics of breast cancer?

Dr. BRODY: It already has, in the papers that came out just a couple of weeks ago, identified additional genes that are responsible for breast cancer, at least contribute to breast cancer risk. I think what's pretty important to emphasize is that breast cancer genetics that we learned about 10 years ago, that variants in BRCA1 and 2 gene are relatively potent risk factors and that they sometimes increase a woman's risk almost eight times for breast cancer.

The new factors that we're just learning about over the next - over this summer and ongoing are relatively mild risk factors, that they just increase the risk a little bit. They still have major importance, because breast cancer is a disease, for the most part, that we don't understand the mechanism yet. And by using the clues from these genes that are showing up in these large single nucleotide polymorphism-type screening, we should be able to better understand what makes the breast cell become a cancer, so mechanism of the disease.

PALCA: All right.

Dr. BRODY: There're really two flavors of breast cancer gene now that the relatively strong risk factors that we knew about 10 years ago, and these new crop of genes that are coming out of these large genome-wide association studies.

PALCA: Well, David Valle, maybe I can ask you. If these risk factors that are turning up with these whole genome association studies are, you know, relatively small compared to some of these other genes that have been discovered, why is there an importance here clinically? What's the value for a physician, let's say?

Dr. VALLE: Well, I think that's a question that we are all very interested in thinking about and taking advantage of this new information. The risk of any one of these may be very small, and we're now in this phase where we have to investigate how we can combine these risks and look at several risk factors and see what happens for the - for a person in terms of combinations of risk factors, in terms of understanding the absolute risk for any given individual patient, which - for getting breast cancer. The second point builds on what Larry Brody just said and that is that even for these variants that identify a small risk, they also identify a particular biological system that may explain something about, in the case of breast cancer, the behavior of the breast cells and which cells - what happens to cells when they develop malignancy. So that they give us greater insights into the biology of the disease, and thereby this deeper understanding we hope will translate into better ways of prevention and or treatment.

PALCA: Okay. We're talking with Larry Brody, David Valle and Aravinda Chakravarti, three genetics research scientists and also people with an interest in treatment. And we're interested in taking your calls at 800-989-8255.

And let's take a call now from Tom(ph) in Boston. Tom, welcome to the program.

TOM (Caller): Thank you for having me. I'm curious what the doctors see as - do they see additional roadblocks now, say a product comes out for, you know, purely looking at the gene, gene therapy type of thing, will the FDA be likely to draw things out, saying that we need further studies because now we have a more advanced outlook of the whole system, or will just-in-time therapies be still allowed for, like, terminal diseases.

PALCA: Okay. That sounds interesting. And, David, maybe I can - David Valle, maybe you can address that?

Dr. VALLE: Well, I think for many of the discoveries that are coming out right now, they are not - they have not identified - they will not lead immediately to the development of new therapy. And certainly they will not lead, I don't think, to new genes therapy. On the other hand, they open new areas of biology, and sometimes, one of the most immediate kinds of therapies, and we've seen this for other generic disorders, is that we may, by having a deeper appreciation of the biological basis, we may recognize that drugs that are already out on the market for some other purpose, already gone through the FDA process, may become applicable or useful or at least worth investigation in new disease - in different diseases that we didn't really realize that those drugs were appropriate for.

PALCA: Mm-hmm. Larry Brody, I just wonder if I can ask you, is that a concern at all that people say, oh, I have this particular SNP and it's associated with breast cancer and I'm doomed. Are you worried that people are going to get the wrong message from these studies?

Dr. BRODY: Well, I would be worried if we had a lot of information. At this point, we don't know how to employ these more mild risk factors in a way to have people either be worried or reassured. And we don't think it's necessarily time to start testing people, potentially left and right, for these variants. So there's potential outcomes of risk assessment if you find out you're not at risk and that should be a good thing, or could be a bad thing, because you'll take additional risk behaviors, or you could find out that you are at risk, and that could be a good thing in that you'd try to do risk reduction. Or you could think that you're doomed because of your gene and go on and do bad behaviors. And we don't know how people will deal with this information yet. So I think the real need here is to try to figure out how people process and handle this information.

PALCA: Yeah. Sounds like some social science research lies ahead.

Well, anyway, we have to take a short break, and we'll continue our discussion about these new whole genome-wide associations. We'd like to hear from you. Our number is 800-989-8255.

Stay with us. We'll be back.

This is TALK OF THE NATION from NPR News.

(Soundbite of music)


We're talking this hour about the genetics of disease. My guests are Larry Brody, he's a senior investigator at the National Human Genome Research Institute, and David Valle and Aravinda Chakravarti, who are both at the Johns Hopkins University School of Medicine with many departmental affiliations so we'll just - we'll save those for the end and tell you about those later.

But we'd also like to hear from you. We're talking about genetics. And our number is 800-989-8255.

And let's take a call now from Gary(ph) in New Hampshire. Gary, welcome to the program.

GARY (Caller): Hello. It's an honor to ask the question. Thank you very much.

PALCA: Sure.

GARY: My question is, currently there is an over-the-counter gene SNP testing kit that allows you to do a cotton swab within your cheeks of your mouth, and you send it back into the lab and it gives you a report back of possible predetermined diseases, anything from bone density issues to cardiovascular and such. And I'm wondering, if you've heard of those, and second, if you have, how accurate they could be?

PALCA: Whoa. Where did you get this? Just in a drugstore, a grocery store?

GARY: There are different doctors I've seen online advertise it on their Web site, also companies like And I heard about this initially in a Newsweek article back, I apologize, I believe it's 2006.

PALCA: All right. That's all right. Let me ask Aravinda Chakravarti, maybe you have some knowledge of this?

Dr. CHAKRAVARTI: Yes. I mean, there are now actually a number of companies that are engaged in what's called direct-to-consumer, you know, advertising and testing for various kinds of genetic influences. Without getting into the details of any of these companies and the tests that they provide, I think it's fair to say that these are early days where any single such test may be unlikely to provide a significant benefit to any given individual.

If you look at, you know, what's really known up until now, it's quite clear that for the major common disorders of our time that affect human beings all over the world, it's not any one genetic alteration, but rather numerous genetic alterations in many different diseases, or many different genes rather, together with specific environmental combinations that puts us at the ultimate risk that leads to the onset of a disease.

We're in the beginning stages of understanding it. And there may come a point in time where specific testing would help, you know, vast numbers of people. At this point in time, genetic testing is best done in those few mutations and a limited number of diseases where the risks to specific individuals are actually fairly high. And the benefits of testing at this current time is really very much up in the air.

But it's completely conceivable that some time in the future, we might be able to, you know, adjust somebody's both behavior and treatment, as well as management of an individual depending on their genetic profile. But we've got a lot of work to do, very interesting work, but a lot of work to do before we get there.

PALCA: So Gary, it sounds to me as if there's quite a bit more work before you can be certain that you'll be getting some value from your expense of whatever they cost to do this.

GARY: Sure.

PALCA: So, Larry Brody, can I ask you? Did I characterize that correctly? I mean, is there - is it worth buying these things yet?

Dr. BRODY: I think as learning more information about yourself, you can't argue that we should prevent people from doing that. But as far as the conveyed benefit and what you should do based on your genotype, we don't have a lot of information about that. I additionally would worry about those - and again, without specifics - offering genetic testing that is linked to telling you subsequent products based on your genotype. We don't have enough evidence to know whether buying these products will improve your health or not.

PALCA: Mm-hmm. Well, that is sort of the goal, I guess.

Dr. BRODY: Yes. No, we would like to get there.

PALCA: Yeah.

Dr. VALLE: Joe, this is Dave Valle. If I could comment on one thing.

PALCA: All right. Sure.

Dr. VALLE: The one exception where the evidence is pretty clear is in certain areas of individual response to certain medicine, so called pharmacogenetics, where there the risks are sometimes quite major, and we know - physicians know of more than 20 different drugs in which there is individual variation in the ability to metabolize those drugs or respond to those drugs. And I think in those instances, that genetic information can be translated into how physicians manage individual patients. But I think rather than dealing with direct-to-consumer kinds of tests, the individual should discuss it with their physician...

PALCA: Right.

Dr. VALLE: ...and ask about whether if they need that medicine, ask whether or not that testing is merited in their case.

PALCA: Right. Right. I can see you'd get into trouble trying to manage all your over-the-counter medications with a bunch of tests for your genetic susceptibility to responding to aspirin or something like that.

Dr. VALLE: Right. Absolutely.

PALCA: Okay. Let's take another call now and go to Neal(ph) in Cleveland. Neal, welcome to the program.

NEAL (Caller): Thanks. My question is, are there any examples of genes or SNPs identified by genome-wide association studies that have actually led to either effective drugs without terrible side effects, or have elucidated the disease pathogenesis in a given case. And the reason I ask is because in my field of histocompatibility, the association between a particular gene called B27, and a disease called ankylosing spondylitis, is much stronger than almost any of the associations being mentioned in this program.

PALCA: Ah, you know, it's an interesting...

NEAL: Can I add to that?

PALCA: Yeah. Go ahead.

NEAL: In spite of that, there isn't a single drug nor is there any complete consensus on the pathogenesis of ankylosing spondylitis. And that association has been known since 1973. I think that helps to put...

PALCA: Well, I - no, it's a fair question.

NEAL: ...these findings, as interesting as they are, into perspective.

PALCA: Right. And - okay. Well, thanks Neal.

David Valle, maybe you would like to comment on that.

Dr. VALLE: Yeah. I would like to. Certainly I recognize the difficulty that people have had in getting to the bottom of ankylosing spondylitis. But there are now increasing examples of the kinds of insights and therapeutic implication from these SNPs, and I would mention two. The first is that the age-related macular degeneration, which I guess now - three years ago, we recognized Jacqueline Ho(ph) and her colleagues pointed out an association with a kind of innate immune - with a variant in an innate immune system called the complement system. And we now know that insight into the pathophysiology of age-related macular degeneration really has completely revised how we think about that disorder and opens the possibility for treating individuals at risk for age-related macular degeneration with anti-inflammatory agents and so forth.

And then the second example is this very strong, variant TCF7L2, which is -increases risk for type 2 diabetes. And I think we're just hearing in the last week or two of papers coming out showing how patients with this genotype, depending on your genotype at this locus, not only increases your risk for diabetes but also your response to standard drugs used to treat type 2 diabetes, such as sulfonylurea. So I think those are two examples, one providing insight into pathophysiology and the other providing insight into treatment.

PALCA: Right. So in other words, finding the association doesn't guarantee anything, but it certainly gives you some options for where to look.

Dr. VALLE: Right.

Dr. CHAKRAVARTI: Well, Joe, this organizes...

PALCA: Go ahead, Aravinda.

Dr. CHAKRAVARTI: I think it's fair to say, in almost every case where there are convincing results from genome-wide association studies, it is now leading down a path in understanding pathophysiology that, not that it was incorrect in the past, but it's clarified one of several directions that we could have taken, and that itself is of great importance.

PALCA: All right.

Dr. CHAKRAVARTI: Let me give you, sort of, two quick examples.

PALCA: Okay.

Dr. CHAKRAVARTI: The question of type 2 diabetes was brought up, and I think all of the recent studies in type 2 diabetes have, sort of, reemphasized the importance that many of the genetic variants involved in fact control into insulin secretion rather than, you know, peripheral resistance. So this is a very, very important idea that was suggested from early genetic studies of rarer forms of diabetes. And the fact that this is coming to prominence, in fact, leads us to investigate questions in that direction that frankly speaking, we had not done in the last decade.

The second, I'd point at something from our own work. We've looked at many features of the EKG that, in fact, predispose some individuals to sudden cardiac death. And we've known for a long time many of the genes that are involved in rare forms of a sudden death syndrome. But many of those genes that were known that are in channels and drugs that are - ion channels, in fact, have proved largely ineffective, and in fact, have led to more side effects than any positive benefit in adult patients with sudden death. And now, genome-wide association studies have shown the importance of a completely new pathway. This is on nitric oxide signaling that in fact explains why previous treatments, in fact, have not proved any benefit and gives us new drugs and treatments and other directions to pursue that really, we couldn't have imagined.

So the great excitement that you hear from many people about genome-wide association studies is giving us much more certain handle, and in fact, often multiple handles for a given disease as to what we should look for specifically.

PALCA: Well, my next guest may have some insight to share with us just on that very topic. We've talking mostly about how these genome-wide association studies have mostly been applied to illnesses.

But this week, for the first time, a study applies the methodology to infectious disease, in this case, HIV infection or AIDS. Tremendous variation exists between how people's bodies respond to HIV. This study out in the journal Science this week suggests that genetic variation plays a significant role in the ability of our immune system to fight the virus.

Here to talk about that study is David Goldstein, a professor of molecular genetics and microbiology at the Institute for Genome Sciences and Policy at Duke University and the senior author on the paper. Welcome to the program.

Dr. DAVID GOLDSTEIN (Professor of Molecular Genetics and Microbiology, Institute for Genome Sciences and Policy, Duke University): Thank you.

PALCA: So which kind of - I mean, what were you looking to use these genome-association studies to predict about the course of HIV infection?

Dr. GOLDSTEIN: Well, the starting point for our work was the well-known observation that individuals vary, as you were already saying just a moment ago, they vary importantly in their vulnerability to the virus that causes AIDS. Some individuals we know are largely resistant to becoming infected in the first place. And we understand some of that, but not all of it. And even for those individuals that do become infected, we know that the majority of them without treatment will eventually progress to AIDS. But it turns out that something like 10 percent of people that are infected, so far as we know, are, in fact, not bothered by the virus at all. They will not progress to AIDS. They are asymptomatic and in other words their immune systems are able to effectively control the virus.

And what we set out to do is use the new technologies that you're discussing on this program to try to identify genetic correlates and hopefully ultimately information about the causes for why some individuals are able to control the virus that well. And ultimately the hope would be, that if you understood that better, you'd use that information to help other people to be able to control the virus better.

PALCA: So, but you are looking at people who were infected, not just to -because I was wondering if you would compare these - the people we've been talking about, the scientists have been talking about, so far, had been people who are infected and people who are not infected, but your whole population are people who are infected. So you're not looking at people to see why some people get infected and others don't?

Dr. GOLDSTEIN: That's exactly right. Our focus was on what happens after individuals become infected. So in a typical course, after infection, the virus will shoot up to a peak level. And after that point, a degree of immune control is established and the virus is pushed back down to a stable level that's maintained often for years, and that level is referred to as a set point for the virus. But that amount of virus during that period varies by a huge amount across individuals. So some individuals, if you look in a milliliter of their blood, they may have as many as a million copies of the virus, whereas other individuals may have only 50 or, in fact, undetectable levels. So that indicates tremendous variation in how well, without any treatment at all, the immune systems of individuals are able to control the virus right to the point that some individuals can control it effectively enough not to become sick.

PALCA: Oh. We're talking with Dr. David Goldstein about his new paper in Science this week about how certain genetic variations predict or help predict whether or not someone will have a large infection with HIV or a relatively small one.

I'm Joe Palca. And this TALK OF THE NATION from NPR News.

So is there, I mean, is there a simple answer that you can point to and say, aha, it's this? And if you've got this, you're in good shape, and if you don't, you don't?

Dr. GOLDSTEIN: It's not one simple answer. But we've certainly taken a few steps towards understanding why some people can control the virus better. So we have found three genetic differences amongst people. One of them was one that was already known before, but we may have some new ideas about how it works. All together, these three genetic differences, if you consider them collectively, on average, make the difference between having something like 50,000 copies of the virus per milliliter of blood versus only 1,000. And they also make the difference between progressing to AIDS more rapidly or less rapidly. So this gives us some ability to predict who would progress more rapidly to AIDS, to predict who would control the virus better.

But that really isn't the main importance of this sort of work, as you were discussing earlier. The main importance from these sorts of genetic studies is to provide pointers to a better understanding of what's going on in the body, and then to make use of that better understanding therapeutically. And so here, what we're excited about is that the genetic research has pointed towards new mechanisms that the body naturally uses to combat HIV.

PALCA: All right. I mean, what's the next step? Now, that you've shown this, what specific thing do you do to follow this up?

Dr. GOLDSTEIN: Well, one - there's a series of directions that we are now following. But one of them is that we've got a new pointer in terms of a vaccine strategy emerging from this work. So one of the ways that the immune system fights an infection like HIV is that the immune system successfully flags infected cells for destruction. And the way that it does that is by presenting bits of the invading infectious agent on the surface. And the genes that are responsible for encoding the machinery, that presents those foreign fragments - those genes can be interfered with by HIV. And the ones that were known previously to be important are known to be interfered with by HIV.

In this study, we've implicated a new one that people did not know was important in the control of HIV. And what's critical here is that HIV doesn't appear to be able to do anything to it.

PALCA: Right.

Dr. GOLDSTEIN: So this suggests that a vaccine strategy that focused on this particular part of the immune system might prove more effective than ones that have been tried before. And so...

PALCA: Okay. Well, I'm afraid, Dr. Goldstein, we're going to have to leave it there. We wish you luck...


PALCA: ...with the future of that vaccine strategy. And hopefully, we'll be able to ask you back when there's something to report on that.

Dr. GOLDSTEIN: Thank you.

PALCA: Dr. David Goldstein is a professor of molecular genetics and microbiology at the Institute for Genome Sciences and Policy at Duke University. Stay with us. We're talking with some geneticists who are at the Jackson Lab this week, and we're talking about whole genome-wide association studies. And we'll be back to talk some more of that in just a minute, so stick around.

This is TALK OF THE NATION from NPR News.

(Soundbite of music)


Coming up, we'll be talking about checkers. Yes, you can finally guarantee yourself not to be able to beat a computer at checkers. But we will talk about that in just a minute.

Right now, we're talking about the genetics of disease. And my guests are Larry Brody, he's a senior investigator at the National Human Genome Research Institute. David Valle, he's the director of the McKusick-Nathans Institute of Genetic Medicine and Aravinda Chakravarti, he is also at the Institute of Genetic Medicine, and they're both at Johns Hopkins University School of Medicine.

And I'd like to go back to the phones now and get some more questions on that. So let's go to Jim(ph) in Chicago. Jim, welcome to the program.

JIM (Caller): Hi. Thanks.

PALCA: Sure.

JIM: I know all these guys' work and that it's really wonderful. But I do and write about nutritional genomics, so the question is, we know that diet and lifestyle are going to affect disease incidence, and yet the genome-wide association studies typically don't assess that. And I'm wondering whether you guys can give us an idea of, if you were to put that data in, to assess it accurately, what the risk factors might do? And then, a related one has to do with the populations you look at. And I looked very carefully at the diabetes papers that came out in Science about, in May, all of those were done in European ancestry or people who were at European ancestors. So the question is, do you expect to find the same set in other ancestral groups?

PALCA: Well, that's a good question. Jim, thanks. Aravinda, maybe we could start with the ancestral question. I mean, are we explaining things for rich, white people again or have we got a more diversified genetic population to do these studies on?

Dr. CHAKRAVARTI: Yeah. So Jim's question, in fact, on both counts are quite pertinent. I think the studies that have gone on have largely just taken use of many of the cohorts that really do exist, and there's no doubt that the vast majority of the cohorts are with individuals of European descent. That is not to say that at least one other major group have not been studied, and these are African-Americans. And I largely am aware of what's going on within the U.S., where - a number of studies and primarily, say, on the cardiovascular disease arena, but also, say, for age-related macular degeneration that was talked about and for diabetes, that these kinds of same genetic variants are being looked at, as well as completely independent screens to see whether there are other new genes that can be identified with these groups. And there's -undoubtedly, there will be both, you know, some reemphasis of the genes that we found as well as many new genes.

One of the aspects that this brings up - and in fact, there's a lot of work going on - is to take into account the fact that individuals who are of African descent essentially arise from a population that is much, much older than other human populations in the world. And so they have much more genetic variation, and the sampling of the genetic variation that we've done, even for people of African descent, in fact, is much more limiting compared to the total amount of variation that they have.

So the two things are going on, of everything that we know to try and test in the groups that we have samples on, as well as trying to increase the repertoire of variations that we can study in African-American groups. And this is going on as we speak. And I am quite convinced that the early studies show that for some of these genes, the same genes have an effect and that'll be different effect in African-Americans. But for many of them, that they don't have an effect, and we have to increase this variation aspect. One quick example, and this really relates to prostate cancer, where there is absolutely no doubt that some of the genetic variants that have been found explained the high risk of prostate cancer at least in African-American studies that have been done.

PALCA: Okay.

Dr. BRODY: Can I just jump in?

PALCA: Is that David?

Dr. BRODY: This is Larry.

PALCA: Larry. Larry Brody, go ahead.

Dr. BRODY: I think Jim probably knows this, but your listener should understand that these variants that we find associated with risk, that the actual variants are present in all population. There are very few variants out of the millions in the genome that are only found in one population. So Jim's question is somewhat nuanced, as to whether they have the same risk in a different population. But the variants will be present across the world.

PALCA: Larry Brody, I wonder if I could just ask you now, since we seem to be at this point. You are working on a project called the multiplex initiative that's trying to weigh the advantages of personalized risk assessment. How is that going to work?

Dr. BRODY: So these projects that we're doing - it's a collaboration between my group and Colleen McBride's group of behavioral scientists - really is to get at some of the very, very early questions about what happens when you give people personalized risk assessment. It's not a study that has enough individuals to decide whether it helps them prevent disease and whether they're healthier in the long run.

It's really a study on how to start delivering this information. And we're enrolling and we'll start returning information in the next couple of weeks, select individuals of who are in Detroit and members of the Henry Ford Health System, it's the third collaborator in this project. But it really is a study aimed to answer questions about how to deliver this information, whether people find it useful, what they do with it. We need to do many, many more studies going forward to figure out whether or not knowing your personal risk variant will actually improve your health. And that's going to take a long time. So we're just taking some small steps forward in this current study that we mentioned for the multiplex study.

PALCA: Okay. David Valle, I'm going to give you the last word on this segment. And the question I want to ask you is: these papers, these whole genome-wide association studies are coming out, you know, at a furious rate. Are scientists really as excited as all that? Or - I know that my editors are already beginning to roll their eyes, it's one a week or two a week or three a week. I can't get anybody to, you know, want to talk about these anymore. Is it too much for the scientists, too? Or is it just a bonanza?

Dr. VALLE: No. I definitely think it's a bonanza. We are very excited. We're here at the Jackson Labs having this 48th Annual Short Course, as you said, and I can tell you that we're packed to the overflow with students. And the students and the professors alike are super excited about this work that's going on. And as I sit here looking out over the spruce forest and hearing about this, if I could sort of encapsulate it for the listeners, it's as if biomedical research has been going down a particular path, focused in on some disease, and we follow this path and - but we get, sort of, committed to one particular path.

And these studies provide a new strategy that looks over the whole forest. And all of a sudden they say, oh, here's another path over here that's actually much more direct and much more effective. And so we're sort of taking this broad view and finding new insights into disease that have tremendous promise for both understanding the disease, developing therapies, and ultimately we hope helping people, inform people about their individualized risk, so that they can - instead of giving them average risks, we give them individualized risks and they can take advantage of this and improve their health.

PALCA: Okay. Well, I guess the trick will be not to get lost as you go down these new paths.

Dr. VALLE: Right.

PALCA: But I'll count on you to do that.

Dr. VALLE: Okay.

PALCA: Right. I'd like to thank my guests, Lawrence Brody. Well, that was David Valle you were just hearing from. He's the director of McKusick-Nathans Institute of Genetic Medicine and professor of pediatrics, ophthalmology, and molecular biology and genetics at Johns Hopkins University School of Medicine. We also spoke with Larry Brody. He's a senior investigator at the National Human Genome Research Institute. And Aravinda Chakravarti, director of the Center for Complex Disease Genomics at the McKusick-Nathans Institute of Genetic Medicine and professor of medicine, pediatrics, molecular biology and genetics at Johns Hopkins University School of Medicine. Thanks to you all.

Copyright © 2007 NPR. All rights reserved. Visit our website terms of use and permissions pages at for further information.

NPR transcripts are created on a rush deadline by Verb8tm, Inc., an NPR contractor, and produced using a proprietary transcription process developed with NPR. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.