Genetics and Hair Loss

Welcome to our webcast. I'm David Folk Thomas. 

You've probably heard people say that hair loss is passed down to men through their mother's side or to women from their father's side and other such genetic theories about how hair loss is inherited. 

But how much real science is there behind these claims? Well, with advances in genetic research, scientists have gained new tools with which to learn about the genetics of loss. What have they discovered so far and what are the possible benefits of this research to hair loss patients? Here to talk about the state of hair loss genetics are two experts. 

To my left is Dr. Angela Christiano. She's an associate professor of dermatology and genetics at Columbia University, and to Angela's left is Dr. Animesh Sinha, he's an assistant professor in the department of dermatology at Weill Medical College of Cornell University and New York Hospital. Thank you both for joining us.

Let me start with you, Angela. Can you tell me some of the ways researchers are studying the relationship between genetics and hair loss?

ANGELA CHRISTIANO, PhD: Sure. I think the past few years have really been a renaissance in studying genetics and hair. For a long time there really was no meaningful way to approach hair loss from the genetic standpoint, and in recent years several groups around the world have started taking a very simple -- what's called a "single gene" -- approach, looking at hair loss sort of one gene at a time, starting first with rare forms of hair loss in isolated families around the world using the techniques of genetics that we've mastered up to now. The challenge going forward is to be able to look at more complex forms of genetic hair loss, like male pattern baldness, and this will involve looking at several genes at one time. So we're just at the cusp now of trying to look at the more common forms of hair loss using the tools of genetics as they become available.

DAVID FOLK THOMAS: Now, you say this is all fairly new. In the past, wasn't it like you thought people went bald because it was genetics, so why is it just now becoming something that they can study genetically, if you will?

ANGELA CHRISTIANO, PhD: The myth that hair loss is passed down from one side of the family or the other was actually started in 1916 by a female physician named Dorothy Osborne, who published a paper saying that pattern baldness was inherited in a certain way. That myth has been propagated through the dermatologic literature all this time. In fact, there is no single way to get hair loss from your parents. We now understand that it is a complex trait, that there's a contribution most likely from both parents, so the genetics of it become more complicated as we understand more about it.

DAVID FOLK THOMAS: And Ani, go ahead.

ANIMESH SINHA, MD, PhD: What is clear is that baldness or male pattern baldness or angiogenic alopecia is genetically based. What's unclear is the exact mode of inheritance. Many models have been proposed, including sex chromosome linked, or it's one particular dominant gene, but what is falling out is that this is a complex trait or condition, and there are likely to be many genes involved, so it's a polygenic trait. That makes it a very difficult trait or condition to study, but as Angela said, now we're starting to get better tools to address these more complex genetic conditions.

DAVID FOLK THOMAS: Angela, I understand that you discovered the so-called "hairless gene." Can you explain that? And congratulations in advance on your discovery.

ANGELA CHRISTIANO, PhD: Well, we'll see.

DAVID FOLK THOMAS: It sounds exciting.

ANGELA CHRISTIANO, PhD: It started a few years back. In 1995 I lost my hair to a disease called alopecia aerata, and this prompted my lab's interest in understand genetics and hair. At the time we were a very small and very underfunded lab, and we wanted to ask a simple question: Can we find one family somewhere in the world with a rare form of hair loss that might just give us some insight into the process somewhere? So our travels landed us on this gene called "hairless," and it has absolutely nothing to do with pattern hair loss as we now know it. It does appear to control one important step in the hair cycle, so in that way it's important in regulation, but right now there's no clear connection.

The goal of doing the single-gene approach to genetics is really to try and form a blueprint to sort of lay the foundation to understand the basics, because up to now we haven't even understood a handful of genes, really, that control hair growth. So at this point we're sort of still laying the groundwork using the single-gene approach, and then work that is going on in Ani's lab will take that and expand it using a more global approach, looking at several genes together and not just one gene at a time.

DAVID FOLK THOMAS: Right before I get to that, did you name the gene "hairless," or how did it come up?

ANGELA CHRISTIANO, PhD: No. The gene was actually named "hairless" in the mouse before we came along, so we inherited this nomenclature from the mouse people.

DAVID FOLK THOMAS: Okay, but directly related to "hair loss," "hairless," "less hair," or is that just a coincidence?

ANGELA CHRISTIANO, PhD: Mouse people tend to name their genes by the way the mouse looks, and in this case the mouse looked hairless, so that's the name they gave it, and it stuck.

DAVID FOLK THOMAS: It sounds sort of like a self-fulfilling prophecy. Ani, as Angela alluded to, the complex gene approach is how do you tie in the study of single genes with each other?

ANIMESH SINHA, MD, PhD: Right. As we've mentioned, male pattern baldness or angiogenic alopecia is more than likely due to the effects of several genes. Now, how do we address that? One is to expand the single gene approach to look across the genome, across all chromosomes at the DNA level, and that would be using specific genetic markers that span the whole genome, and look for linkage or association in certain affected individuals or family members.

Another approach, which my laboratory is beginning to take, and I'm sure others are trying as well, is to look directly in tissues and to look at what genes are actually expressed in, say, balding scalp versus hair-bearing areas, and then to try and document which genes are turned on or off, or up- or down-regulated, and correlate those with the initiation and progression of the condition. So in order to do that, the technology that has allowed us to step forward to this point is something called microarray or DNA chip technology.

DAVID FOLK THOMAS: The gene chip I've heard about?

ANIMESH SINHA, MD, PhD: Exactly. The so-called "gene chip." What gene chips are, really, is an intersection between biology and computers. So on a glass slide, we can spot or synthesize thousands or tens of thousands of genetic sequences in a grid-like fashion and then monitor their expression simultaneously. So that takes us several steps forward in addressing genetic issues at the tissue level. Previously, people could look at gene expression in one or a few sequences, but now we can go orders of magnitude higher, and we're at a phase right now of just accumulating data to try and find out what genetic sequences, what genes are relevant to a particular disease such angiogenic alopecia.

So we're still at the phase of gene identification. From there, we'll have to go to validating these suspected disease-related sequences, and ultimately we want to identify or define gene or protein targets for drug discovery so we can intervene in the condition.

DAVID FOLK THOMAS: So would that be one implication, or are there other implications -- Angela, you can feel free to answer this -- of all this genetic research?

ANGELA CHRISTIANO, PhD: I think that's probably at this point the most relevant, that we'd like to be able to look globally at a whole expression profile in given tissues to look at trends, to look to see where there are common pathways that are influenced in different patients, and then when we think about taking that forward to the next step, designing therapies, again, if there are six or eight or ten genes involved, we don't yet know whether we'll have to up-regulate some, down-regulate some, which ones will be most important. So once the genomics is worked out in several genes using gene tips, the next step is pharmacogenomics, learning how to take that information and design meaningful therapies, so it's an extremely exciting time, not just in hair but in all of genetics, because finally the tools to give us the power to do this are at hand.

DAVID FOLK THOMAS: I know there's probably not an exact answer. It might not be fair to pitch this to you.

ANGELA CHRISTIANO, PhD: We know what you're going to say.

DAVID FOLK THOMAS: And don't hold her to this, but as far as the time frame and for these next steps, is there any ballpark figure for that?

ANGELA CHRISTIANO, PhD: I think for the genomics part, certainly now that the chips are available, within the next few years we should have good baseline gene expression profiles for what genes are involved. Together with that, we also need to think about doing genetic studies in patients and families with baldness, and the approach to that is collecting affected pairs of siblings with different forms of hair loss to begin to look in those patients what genes are inherited, and trying to match up the genetic information with the information from the chip. So I think I would guess maybe within the next five years that we'll at least be on the road to gene chips and linkage. Translating that to the pharmacy store shelf is way far down the road, but I would safely say in our lifetimes it should be something that gene therapy is approachable.

DAVID FOLK THOMAS: And if you're watching this 10 years from now, we're taping in the year 2001. Ani, briefly, the last word to you. We're going to wrap up now.

ANIMESH SINHA, MD, PhD: I think Angela's point is very well taken. I think to move forward, what's exciting is, I think, we're taking integrative approaches with different technologies, looking at the DNA level, looking at the RNA or gene expression level, looking at the protein level, and with the new advances in molecular and computer modeling of proteins and combinatorial chemistry, all these new technologies in the scientific universe give us a better arsenal to comprehensively, collectively as scientists go after what are the genetic causes, and I think hopefully that will all come together in the next few years.

DAVID FOLK THOMAS: Great. Angela and Ani, I want to thank you. That's all the time we have today on genetics and hair loss. I'm David Folk Thomas. We'll see you next time.