Name ______Jennifer Jin_________

LS7B Week 3 Lab Worksheet

You are a genetic counselor and a couple has come to you for advice. They have a family history of cancer and are
concerned that their unborn third child will also get cancer. They provide you with the following pedigrees for two
different traits relating to defects in the enzymes separase and topoisomerase:

These two pedigrees represent the same family. Genetic testing shows that individual 4 has only nonmutant alleles of
both genes and individual 12 has only mutant alleles of both genes. Individuals 6, 8, 9, 12, and 14 have cancer. The
couple just recently learned that their daughter (individual 14) has cancer and has both mutations. In this lab activity,
you will use genetic hypothesis testing to determine the probability that the couple’s third unborn child will also inherit
both mutations and be at risk for developing cancer.

Part 1. Now that you’ve had some practice with using Punnett Squares in the week 2 lab and class, let’s examine the
pedigrees presented above a bit further.

1. Let’s start by figuring out what kind of trait is caused by the separase mutation. Test each of the four possible
hypotheses (X-linked dominant, X-linked recessive, autosomal dominant, autosomal recessive) and determine which
hypothesis cannot be rejected. Write your final solution with a brief explanation.
The hypothesis that mutant separase is dominant can be rejected because the cross between parents 3 and 4
who are unaffected had an affected child. This means that one of the parents or both have to be heterozygous, and
since neither parent is affected, the mutant gene has to be recessive.
The hypothesis that separase is an autosomal recessive can be rejected because since Parent 4 is homozygous
dominant, then Parent 3 has to be heterozygous, but that means that all their children have to be unaffected. Since
they have an affected son, we can say that the XY parent (4) is forced to give the Y and the XX parent(3) gives the son
the mutant X. This means that the hypothesis that separase is an X-linked recessive cannot be rejected.
2. Having determined which pattern of inheritance cannot be rejected, what is the chance that individuals 11 and 12
would have a child affected by the separase defect?

3. Now let’s figure out what kind of trait is caused by the topoisomerase mutation. Test each of the four possible
hypotheses and determine which hypothesis cannot be rejected. Write your final solution with a brief explanation.
Because parent 8 and parent 9 are both affected but have an unaffected child, it means that the topoisomerase
mutant allele is dominant, which rejects the hypothesis that the topoisomerase mutation is autosomal recessive and
X-linked recessive.
Because parent 12 has only mutant alleles, and parent 11 has only normal alleles, then all their offspring will
have to be heterozygous and since the mutant alleles are dominant, all the offspring have to be affected. But
because their son is unaffected, that means that the mutant allele was not transferred from the XY parent to the son.
This rejects the hypothesis that topoisomerase mutation is autosomal dominant. SO because the parent XY 12 gave
the son the Y, the son can only get the nonmutant allele from the mother.

4. Having determined which pattern of inheritance cannot be rejected, what is the chance that individuals 11 and 12
would have a child affected by the topoisomerase defect?

5. Based on your work so far, what is the overall probability that individuals 11 and 12 will have a child affected by both
separase and topoisomerase defects?
If their child is a son, then there is a 0% chance that the child will be affected by both separase and
topoisomerase defects. But if their child is a daughter, then there is a 50% chance that the child will be affected by both
separase and topoisomerase defects. That means that the total chance for an offspring from individuals 11 and 12 to be
affected by both separase and topoisomerase defects is a 25% chance.