Multifactorial Gene Disorders: Examples

00:01 Previously, we’ve talked about how we might tease out some of the genetic contribution of multifactorial gene disorders and pick it out from the environmental components.

00:15 But probably what you really want to get to is what you really need to know for the exam and some of the common examples. So that’s what we’ll cover in this lecture. First of all, we’ll look at some multifactorial disorders that clearly have a genetic contribution but we don’t really know what it is. Then in the second section, I’ll cover some disorders that we are actually ascertaining what the genetic connections are. Now clearly, because we have the human genome sequence done and sequencing costs are coming down and down and down, we’re going to learn more and more about where all of these genetic disorders might lay. But prior to now, it’s been exorbitantly expensive to just do a genetic screen on everyone. Let’s move on and look at the three main types of disorders that I’ll cover in the beginning of this lecture where we know there is a genetic component but we don’t know what it is. We have some congenital heart disorders. There’s actually a lot of those that we have quite a good understanding about as well as neuropsychiatric disorders.

01:29 We’re going to look at schizophrenia and bipolar disorder. Finally, we’ll look at coronary artery disease.

01:36 As you've probably heard, it potentially has some genetic links, so why not discuss those here.

01:43 We’ll begin by looking at some congenital heart disorders. These are a specific subclass of congenital heart disorders that have to do with flow through the heart. I bring them up not because you should know the values or the symptoms or any of that, just because there are some disorders associated with genetics. Again, we are having this value, the lambda.

02:12 You’ll recall that lambda was a value that we could use to discern the genetic component based on the presence of the disease in related individuals relative to the presence in the general population. You can see that there are some fairly significant lambda values.

02:33 We’ll look briefly at atrial septal defect where the septum between the atria doesn’t seal properly.

02:43 It’s a fairly common disorder. You can see that it has a lambda value that’s fairly significant suggesting a genetic component. Then we can see aortic stenosis also has a genetic component.

02:58 This is a valve disorder. Again, that’s not the content of this course but recognizing that some congenital heart disorders, particularly these ones associated with flow during development have a genetic component and revisiting that lambda value. We also have now noted that there are some neuropsychiatric disorders. This one I find particularly interesting.

03:27 It’s always shocking but it’s estimated that about 1% of the world’s population has schizophrenia which when you think about your friends, could be kind of a funny statistic to think about.

03:41 But anyway, this is a multiple personality of varying degrees but it’s suggested certainly that there’s a genetic component. When we look at twin studies, we have monozygotic concordance and dizygotic concordance that is much less suggesting that there’s a strong genetic component.

04:03 Now again, I want to bring up this concept of statistics. No matter what source that you consult, you are likely to run into statistics that disagree with each other. You’ll notice here in this slide, I was going to fix it but why, because it's the truth of the matter. We’ll see 17% versus 10% to 16%.

04:23 The point that you really need to take into consideration is not memorizing the values but logging in that there is a much lower frequency of dizygotic concordance than there is monozygotic concordance.

04:37 So, my advice would be look more at the size of the bars rather than the specific values.

04:42 That goes for any statistic in genetics because as you’re learning, it is really hard to tease out all of the details. The big question then is where are these genes? I believe in the study of schizophrenia and some of the other disorders that we are looking into, we are going to be experiencing a gold mine as we start seeking through the genome for the actual genes behind many of these disorders. Obviously, it’s not purely genetic. It’s multifactorial and probably multiple genes involved but clearly, there is some kind of component. Everybody really wants to know what these genetic components are for a variety of different reasons.