3
$\begingroup$

I'm doing old exam assignments to prepare for my finals on Monday and I've stumbled on one assignment that I'm not sure how to tackle.

A family with 2 children is examined for cataracts using PCR with 4 markers, A, B, C and D. The results are seperated on a gel and the genotypes are as follow:

enter image description here

Where Far = father, Mor = mother, Barn = child.

Notice that there was an error with the analysis so child 2's alleles are undetermined.

The question states: Draw a pedigree with each of their haplotypes. What is the most likely haplotype of child 2?

I don't understand exactly what it's asking. I'm not sure what a HAPLOtype is. I know what a genotype is and that is what the answer seems to indicate.

The answer for the father is: 4 3, 1 2, 11 5, 7 4. Now the only difference between these numbers and the given numbers are the re-arrangement of 5 and 11 in marker C?

$\endgroup$
  • $\begingroup$ The first paragraph of the Wikipedia article should help - it's the combination of alleles inherited from one parent i.e. on the same chromosome. It derives from haploid genotype. $\endgroup$ – blep Jun 4 '15 at 19:53
  • $\begingroup$ I still don't understand the assignment. What do the numbers mean exactly? Are they related to this picture and if so what does each number represent in terms of letters on the picture? i.imgur.com/0yiiBrP.png $\endgroup$ – Paze Jun 5 '15 at 15:51
  • $\begingroup$ all you need to solve the problem is to know they indicate different marker alleles. The alleles could be due to a variable number of repeats at the loci (see microsatellites and variable number tandem repeats on Wikipedia for examples if you are interested), but that information is not necessary to solve the problem. On your picture, the markers could be any of the alleles. $\endgroup$ – blep Jun 5 '15 at 17:11
  • $\begingroup$ Why do they occasionally switch between the numbers when writing the haplotypes? In the diagram the father has: 3,4 1,2 5,11 4,7 But the answer for the haplotype is 4,3 1,2 11,5 7,4 Why is the 11 and 5 re-arranged when telling his haplotype? This is pretty much the only thing left that confuses me. $\endgroup$ – Paze Jun 5 '15 at 17:20
  • $\begingroup$ I think that is supposed to mean 4, 1, 11, and 7 are on one of his chromosomes, but I've not seen it written that way before (or I don't remember it). I am not sure how you can figure out the parental haplotypes in this case, either. You can figure out which alleles are inherited by each child from each parent (the child haplotypes), but I don't think this would give you the parent haplotypes, unless you are assuming meiotic recombination does not occur. (eta: I haven't worked out the problem yet) $\endgroup$ – blep Jun 5 '15 at 17:30
2
$\begingroup$

Definition of Haplotype

The concept of haplotype has the default to be subject to several definiton that differs mostly by their complexity to be understood and by their specificity but different definitions also sometimes differ slightly in their meaning.

In simple terms the concept is pretty easy. A haplotype is a porte-manteau word of haploid genotype and it refers to half the genotype.

What the question is asking

The question is asking is Here is half of the genotype of the child, what do you expect the other half to be?. Note however, that for the last two markers, the first haplotype is not indicated so they are just asking for the genotypes here which makes the question slightly poorly phrased IMO.

The answer key

The answer concern the father, which is silly as the question is about the child. So the answer you stated definitely does not answer the question.

The answer

We have to look marker per marker to answer the question and then consider them all together to reconstruct the haplotype. In absence of information on the subject, we are going to assume that the markers are completely independent (unlinked, eventually on different chromosomes). We will also assume no mutation (probably negligible anyway) and we assume no crazy kind of inheritance such as some selfish elements. You will note also that information about the first child tells nothing about the second child.

Marker A

The first allele inherited necessarily comes from the mother and therefore, the second allele must comes from the father. As a consequence the second allele is either 3 or 4 with equal probability.

Marker B

The first allele inherited necessarily comes from the father and therefore, the second allele must comes from the mother. As a consequence the second allele is either 1 or 4 with equal probability.

Marker C

The four possible genotype are [5,7], [5,11], [11,7] or [11,11], that all occur with equal probability. This means that for Marker C, at one haplotype, the probability of being 5 or 7 is $\frac{1}{4}$ and the probability of being 11 is $\frac{1}{2}$.

Marker D

The four possible genotype are [4,7], [4,8], [7,7] or [7,8], that all occur with equal probability. This means that for Marker D, at one haplotype, the probability of being 4 or 8 is $\frac{1}{4}$ and the probability of being 7 is $\frac{1}{2}$.

Whole Haplotype

From the above, you can compute all possible haplotypes and calculate the most likely to occur. However, there are some ties. The most likely genotypes are (3,1,11,7), (3,4,11,7), (4,1,11,7) and (4,4,11,7) that could occur with probability $\left(\frac{1}{2}\right)^4 = \frac{1}{16}$.

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.