Exercise 1

For each pedigree, determine the most probable inheritance pattern, assuming monogenic inheritance and full penetrance.

Pedigree 1



Pedigree 2



Pedigree 3



Pedigree 4



Pedigree 5



Exercise 2

A 25-year-old healthy woman seeks genetic counseling for a hereditary skin condition, ichthyosis, which is present in her family. Ichthyosis is characterized by dry, thickened, “fish-scale” skin.

  1. Draw the pedigree for this family.
  2. What is the most likely mode of inheritance for this disease? Justify your answer.
  3. The woman begins a relationship with her father’s brother’s son. If they have children, what is the probability that their child will inherit ichthyosis? (Hint: Use a Punnett square to determine the risk.)



Exercise 3

In the pedigree below, filled symbols represent individuals affected by chronic granulomatous disease.

  1. Assuming the disease is X-linked recessive:
    1. Which individuals are obligate carriers of the disease-causing allele?
    2. How should obligate carriers be indicated in the pedigree?
    3. What is the probability that individual II-4 is a carrier of the disease-causing allele?
    4. What is the probability that individual III-1 will develop the disease?
  2. Assuming the disease is autosomal recessive, and individual II-5 is not a carrier:
    1. Which individuals are obligate carriers of the disease allele?
    2. What is the probability that individual II-4 is a carrier?
    3. What is the probability that individual III-1 has inherited the disease-causing allele?
  3. Assuming the disease is autosomal recessive, with a population disease frequency of 4 in 10,000:
    1. What is the probability that individual II-5 is a carrier?
    2. If you take the above risk into consideration, what is then the risk that III-1 will get the disease?



Exercise 4

What is the genetic distance between locus \(A\) and \(B\) in the three examples below?



Exercise 5

The two genetic marker loci, \(A\) and \(B\), are located on chromosome 9, with a genetic distance of 15 cM between them.

The father is heterozygous at both loci, carrying the haplotypes \(A_1B_1\) and \(A_2B_2\). The figure below illustrates chromosome 9, depicting both loci and their respective alleles.

  1. Draw a similar chromosome set and position the father’s alleles.
  2. Describe the different gametes that the father can produce and account for the frequencies of these gametes.



Exercise 6

A monogenic hereditary disease is present in the pedigree shown below. A marker locus located in the first intron of the disease gene has two alleles, A and B. The genotypes for this marker locus are provided for individuals II-2, III-2, and III-3 in the pedigree.

A. Based on the available genotype data, can we determine which marker allele (A or B) is located at 0 cM distance to the disease allele? Justify your answer. B. If we assume that II-1 has the genotype BB, does this allow us to conclusively determine which marker allele is linked to the disease allele? C. If the fetus IV-1 has inherited the disease allele, what genotype is expected at the marker locus?



Exercise 7

Assume an X-linked recessive monogenic disorder with full penetrance.

  1. Based on all the information in the pedigree below, what is the probability that II.3 is a carrier of the monogenic disease-causing allele? (Hint: Use Bayes theorem)



Exercise 8

Among Danish women with breast cancer, 3% carry a pathogenic variant. Sanger sequencing detects pathogenic variants in BRCA1 and BRCA2 with 80% sensitivity.

Lise, who is of Danish descent, underwent Sanger sequencing for BRCA1 and BRCA2, and no pathogenic variant was detected.

  1. What is the probability that Lise is still a carrier of a pathogenic variant in BRCA1 and BRCA2 despite the negative test result?