Autosomal Dominant Inheritance

by Georgina Cornwall, PhD

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    00:01 With that being said, now we move on to autosomal dominant inheritance. You can see here that it has a different expression pattern. If you carry the allele, the dominant allele, you are affected.

    00:18 That’s why it’s considered dominant. Here, you can have a carrier. We have the same cross, carrier mother, carrier father. In this case, they will have mostly affected children because anyone actually having the allele which is ¾ of the family will end up with that disorder. In that sense, these are much more prevalent disorders. Here are two types of matings that could lead to affected offspring.

    00:53 Keep in mind that anytime there is uppercase D, the individual is affected. In our first cross here where we have a heterozygous parent and a homozygous recessive parent, we will see that 50% of the individuals are affected, so we have a probability of 50% of offspring being affected.

    01:19 In this next cross, you think about this one if both parents are heterozygous as they were in the earlier figure.

    01:27 We have a ¾ possibility or 75% possibility that the offspring will be affected by this particular disorder.

    01:36 Now again, there are a number of different disorders but they all exhibit this very common Mendelian inheritance pattern. Dominant conditions in general have a higher incidence.

    01:49 Not because those alleles are necessarily more frequent, it’s because if you have the uppercase letter, the dominant allele, then you are going to express the disease. There are going to be more of the dominant alleles in the population. Otherwise, they wouldn’t be called the dominant allele, right? An example that we can look at here is polycystic kidney disease. In certain populations, we might see a higher frequency of the alleles. One in one thousand individuals in the United States will display polycystic kidney disease but not familial hypercholesterolemia. We do have hypercholesterolemia but in the US, it’s not necessarily so much familial. But in the Afrikaners populations of South Africa, we see as high as a one in one hundred incidence because the frequency of that allele in the population is much greater than it is in say, the United States or Europe. So, we need to consider the frequency of alleles. That will certainly come up in future lectures when we look at calculating allelic frequency and populations. Here, I just wanted to draw your attention to the fact that we could have a different frequency in different populations for autosomal dominant inheritance patterns.

    03:20 We could have different frequencies for the other inheritance patterns also but especially autosomal dominant.

    03:27 Here is a pedigree for pure dominant disorder. We’ll cover in much more detail in a later lecture is Huntington’s disease. It’s a purely dominant disease. One of the characteristics of purely dominant disease is it will show up in every single generation and again, equally between the sexes. When you see a pedigree showing up in every single generation, you know that it is an autosomal dominant inheritance pattern.

    04:00 Also, in dominant inheritance, we can have incomplete dominance. You will recall from when we looked at Mendelian genetics that, so maybe you remember, there was complete dominance, incomplete dominance, codominance. Here, we’re looking at incomplete dominance.

    04:24 Something you might remember are the pink flowers and intermediate phenotype.

    04:30 So, sometimes in these human disorders like in achondroplasia, we see this incomplete dominance where an individual that’s heterozygous may not actually be that affected, right? Individuals that are heterozygous display the trait but it is not a lethal trait or anything. It’s a short-limbed dwarfism characterized by a larger head. It’s due to a mutation in the fibroblast growth factor.

    05:04 Now, if you happen to be autosomal recessive for this disorder, it turns out to be fatal.

    05:11 As you can see in this pedigree, the individual in the lower right, so individual Roman numeral III, Arabic numeral 3 is deceased because they were homozygous for this condition.

    05:25 Again, we see another way that the ratios or proportions or probabilities can be altered because of difference in expression, to go along with penetrance and expressivity and all the other things that we need to keep in mind. Let’s now look at another manifestation to add more complexity to how things are inherited. Autosomal dominant traits can be sex-limited.

    05:59 In this case, we have male precocious puberty because it’s another disorder that you should know.

    06:05 I don’t know if you’ve picked up on it by now. But as we’re touring through all these different types of anomalies, I like to bring up things that are perhaps going to be covered on your exams.

    06:17 Male-limited precocious puberty shows up in males only. You can see that it’s dominant because it’s in every single generation. However, it’s only in the males but how do we know that it’s really not an X-linked trait, right? How do we discern this from an X-linked trait? One of the ways we can discern it from an X-linked trait is that we see there’s a male-to-male transmission.

    06:52 That means that it’s autosomal and not X-linked. We also see these two things, right? We also see that there’s transmission through a carrier female that’s not showing it, right? Because it’s dominant, if she has it, she should show it. Those two things in combination let us know that this pedigree is exhibiting something that is X-linked dominant but sex-limited, so again, more complexity to add to the story. I hope you’re keeping all these things straight. Understanding inheritance can clearly get very complicated. As I’ve mentioned before, we have incomplete penetrance and variable expressivity as well as all these other conditions, sex linkage or sex-limited that we have to consider.

    07:54 We need to take all of these things into account in our genetic counseling. So you can see how difficult it probably is to put together a pedigree in full understanding of the disorders that are in place.

    08:09 That’s probably entirely why the whole field of genetic counseling has arisen. Luckily these days, doctors have to do a limited amount of genetic counseling. Then we turn it over to the genetic counselors to do the specific work. Also, we’re much less reliant on constructing pedigrees these days because we have so many more advanced genetic techniques like genome sequencing and probing for particular genes. We can look for genetic markers and so on and so forth.

    08:45 All in all, we need to understand the pedigrees for the exams. But the truth of it is that as we move forward and things expand exponentially, our techniques become much more robust.

    About the Lecture

    The lecture Autosomal Dominant Inheritance by Georgina Cornwall, PhD is from the course Single-Gene Disorders.

    Author of lecture Autosomal Dominant Inheritance

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD

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