Phenylketonuria (PKU)

by Georgina Cornwall, PhD

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    00:00 Let me give you one more concrete example mainly because this is a condition that you need to know about, phenylketonuria. I promised that I’d bring it back to you and give you more details on it.

    00:13 Rather than just listing all the different conditions, I prefer to address them while talking about other specific concepts. Hardy-Weinberg is a good place to bring up phenylketonuria.

    00:24 It ends up that we have phenylalanine converted in a metabolic pathway to tyrosine and then melanin, and so on and so forth down the line. In the case of phenylketonuria, we end up with a build-up of phenylalanine which turns out to be quite toxic especially to the nervous system and end up with phenylalanine ketones in the urine. That is a problem, not so much the urine but the neurological stuff.

    00:57 Now, this build-up of phenylalanine, because we can stop that build-up of phenylalanine by excluding phenylalanine from the diet, this is one of those things that we test for in newborns to make sure they don’t have this condition because we can avoid any kind of mental retardation.

    01:17 My friend’s daughter, Abigail is affected with phenylketonuria. I’d like to use her as an example to practice some calculations of Hardy-Weinberg types of questions that are applicable to our field of medicine. Only homozygotes and compound heterozygotes, recall that anytime a condition is recessive to be homozygote, generally it’s going to involve two different mutations at the same locus because it’s very uncommon to have a high frequency of recessive alleles.

    02:02 We will identify this as q squared. Does it make sense why I’m choosing q squared here? Okay, you could choose p squared but q squared is generally the one we’ll use for homozygous recessive. But so long as you keep your info straight, you’re good with either way.

    02:22 Just q squared is the convention for autosomal recessive. Now, I would like to help out Abigail here and ask some questions. Let’s imagine that Abigail who is homozygous recessive is wanting to get married to a man. She wants to know what her probability is of finding a mate who also has PKU because that could be a problem. That would mean that she might have a child with PKU also.

    02:57 Perhaps she wants to make the choice not to do that. First of all, we need to know the frequency of PKU in the population. Again, the statistics can vary. But in general, the frequency is about 1/10,000 births are affected with PKU. You can clearly then convert that into an actual frequency number.

    03:24 So, we can now say that q squared is 1 out of 10,000. That means q is going to equal 1 out of 100 or 0.01.

    03:37 So, we have a frequency of 0.01 in our population. Go ahead and calculate out what the value would be for p based on our understanding of what q is. As you can see here, indeed, we do have 0.99, pretty simple.

    04:01 We know that p + q = 1. That’s pretty simple calculation, right? Now, we can take that and ask the question what the frequency of a heterozygote, Abigail’s questioning, right? What is the possibility that she marries a man who is a carrier of this allele or we could calculate what is the possibility of him actually having PKU. But the carrier is the incidence because if you think back to a Punnett square, what are we going to end up as the probability of if he’s a carrier and she’s affected, right? If he’s a carrier then there's a 50% chance that she could end up with an affected son or daughter. When we calculate this out, you plug and chug. Are we getting the routine now? 2 x p x q, we see 0.02, which when we translate that to a percent is a 2% chance of Abigail finding a husband who carries PKU. Well, that’s not a very high chance.

    05:13 But should that happen, let’s take it one step further, what are the chances that Abigail would have an affected or PKU child? We’re going to go back to our probabilities problems that we looked at when we were in molecular genetics. If you need to review on that, that’s a great place to go.

    05:40 But if we have a 2% chance of her husband being a carrier and I already covered that if he is, there’s a 50% probability of him passing on the allele to one of her children or one of their children which is pretty high. We roll the dice, this happens to be an and probability.

    06:02 Recall we could have an and/or probability. Here, we’re looking for the husband that is a carrier and them having a child together. Otherwise, it wouldn’t be a probability. So, we can solve this probability problem by multiplying 0.02 x 0.50 and end up with a 0.01 or a 1% chance that Abigail could have a child affected with PKU. Now, that’s not a very high frequency.

    06:36 But she might want to have genetic testing done for her husband to ensure that if she did marry, that he isn’t a carrier. What’s one other thing we might want to have done if she does decide to become pregnant with this man and he is a carrier? Think about the other options, right? Perhaps she wants to have preimplantation diagnosis done or perhaps she needs to have another set of techniques. There’s a whole array of choices that you would have as her doctor or her genetic counselor of choices once you’ve calculated these frequencies.

    07:19 Now, you can see that there’s some relevance to calculating and understanding Hardy-Weinberg equation and Hardy-Weinberg equilibrium.

    About the Lecture

    The lecture Phenylketonuria (PKU) by Georgina Cornwall, PhD is from the course Population Genetics.

    Author of lecture Phenylketonuria (PKU)

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD

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