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Autosomal Recessive Inheritance

by Georgina Cornwall, PhD
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    00:01 In this lecture, we’ll be visiting both autosomal recessive inheritance and then autosomal dominant inheritance. First, we’ll cover the recessive inheritance. Now, autosomal recessive diseases occur in individuals who have two mutant alleles. You’re probably familiar with that. Usually, autosomal recessive diseases are loss of function diseases. On occasion or regularly in the heterozygote, there’s some compensation. They may have half the gene product but in the case of sickle cell for example, you will have compensation. The individual is carrying the sickle cell allele, half of their hemoglobin will be of the sickle cell variety. Half of it will be of the regular variety. This is enough to get by.

    00:54 So, that’s what we mean by compensation. Having two recessive alleles in that case is fatal.

    01:02 But it’s not always fatal. It’s just the recessive condition expressing the actual phenotype.

    01:09 In these types of matings, we end up having unaffected individuals, carrier individuals. You can see both the son and daughter in the middle. Affected individuals, usually ¼ will be affected in a mating between two heterozygotes. Let’s take a look at three possible matings. First of all, you could have both heterozygous parents as we just saw in the last graphic. Here in the Punnett square, we can see that we result in indeed ¼ affected individuals. Now, we don’t have enough offspring like Mendel did with peas to really consider that ¼ of the offspring would have this. So, if we’re dealing with 1,000 pea plants, that’s one thing. But as individuals or parents, maybe we’re lucky to have four.

    02:06 You may see that one in four is affected. We call it a ¼ probability that you would have an affected child.

    02:16 We can work with probabilities because there’s also a ¼ possibility of a son. Anyway, we’ll move further into that as we look at sex linkage. The next scenario that we can look at is having a heterozygous parent and a homozygous parent, in which case, ½ of them would be affected in the homozygous recessive state.

    02:43 The final way that we could have affected offspring, of course, is between two homozygous recessive individuals. In which case, the probability of them having a homozygous recessive child is 100%.

    02:57 They’re pretty much guaranteed; so three different ways. Autosomal recessive pedigrees have a characteristic appearance. So when you’ve taken a pedigree and you’re observing the pedigree, you can predict what sort of inheritance pattern it is and then perhaps do further testing to discern precisely what that inheritance pattern is or what the genotype behind it is. In general, what you see is in this case, both parents are carriers. We can predict that it’s a recessive inheritance pattern because we see that about one in four offspring is affected. They’ve shown six here. But the purpose is to also show that males and females are affected equally. Again, it’s a probability. You could see more or you could see none. The probability could be about one in four affected. Then let’s look at an example.

    04:04 Cystic fibrosis is probably a condition that you are pretty familiar with. Cystic fibrosis results from having a mutant transport protein that you may not be so familiar with. This chloride transport protein, is when it’s functioning, it acts to transport chloride outside of the cell membrane. Let’s say we’re looking at the respiratory passage. The chloride is transported outside of the cell membranes and into the respiratory passage.

    04:42 That chloride acts to draw fluid out of the cells and keep the surface fairly well-lubricated.

    04:49 Now, in the case that we have a broken transport protein or it doesn’t make its way into the membrane, the protein is made but it doesn’t lock into the membrane properly and doesn’t transport chloride ions then we have an osmotic battle in which chloride is not out there. So, it’s hypotonic out there.

    05:11 We end up having much more mucus and thicker mucus and thus the effects that we see with cystic fibrosis, so cystic fibrosis transport protein, CFTR. One in two thousand children approximately is affected by the cystic fibrosis transport or protein issue which is fairly frequent but actually not too frequent considering that one in twenty three people are silent carriers. So, they’re carriers of it because it’s an autosomal recessive condition, they don’t express the condition. If you think about it, one in twenty three people seems like a lot. But this one in two thousand statistic is based on if you have one in twenty three people, what is the chance that that person will mate with one in twenty three of the other sex and produce an offspring. That statistic comes out to be approximately one in two thousand incidences. When you’re calculating these sorts of outcomes, you want to consider both the probability of having the allele and the probability of running into someone else in the population with that allele and reproducing with them. That’s sort of the mission of using pedigree analysis for the field of genetic counseling. On occasion, we’ll see that autosomal disorders are sex influenced. Just as we could have penetrance and expressivity issues, there are more things to cloud our vision on what’s really going on. I bring this up because hereditary hemochromatosis is one of those disorders that is expressed almost exclusively in males and very rarely do we see this in females, like five to ten times more likely in a male. I also bring this up because it is probably the most common hereditary disorder even though it’s mostly expressed in males. We’re not entirely sure why but what this disorder is is an enhanced absorption of iron so that there’s way too much iron in the system.

    07:48 That causes an iron overload which causes coloring of certain organs. They get very pigmented with iron pigment.

    07:57 That causes serious damage in some organs. Some organs are just pigmented. Other organs like the heart, liver, and pancreas get serious damage from it. Of course, if we know that someone has this disorder then we can treat for it and keep the iron levels low in the diet and not have the organs affected.

    08:18 Here’s a quick flash of organs that are affected by the chromatosis, the coloring. But again, only the heart, liver, and pancreas have a really serious condition with it. Hereditary hemochromatosis, one of the most common autosomal recessive disorders or hereditary disorders of the autosomes.

    08:42 Keep that one in mind for your exams for sure.


    About the Lecture

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


    Included Quiz Questions

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    1. Chloride channel transporter defect
    2. Potassium channel transporter defect
    3. Glucose channel transporter defect
    4. Iron channel transporter defect
    5. Phenylalanine channel transporter defect

    Author of lecture Autosomal Recessive Inheritance

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD


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