Chapter 4, Problem 2CS

Pedigree analysis is a fundamental tool for investigating whether or not a trait is following a Mendelian pattern of inheritance. It can also be used to help identify individuals within a family who may be at risk for the trait.

Adam and Sarah, a young couple of Eastern European Jewish ancestry, went to a genetic counselor because they were planning a family and wanted to know what their chances were for having a child with a genetic condition. The genetic counselor took a detailed family history from both of them and discovered several traits in their respective families.

Sarah’s maternal family history is suggestive of an autosomal dominant pattern of cancer predisposition to breast and ovarian cancer because of the young ages at which her mother and grandmother were diagnosed with their cancers. If a mutant allele that predisposed to breast and ovarian cancer was inherited in Sarah’s family, she, her sister, and any of her own future children could be at risk for inheriting this mutation. The counselor told her that genetic testing is available that may help determine if this mutant allele is present in her family members.

Adam’s paternal family history has a very strong pattern of early onset heart disease. An autosomal dominant condition known as familial hypercholesterolemia may be responsible for the large number of deaths from heart disease. As with hereditary breast and ovarian cancer, genetic testing is available to see if Adam carries the mutant allele. Testing will give the couple more information about the chances that their children could inherit this mutation. Adam had a first cousin who died from Tay-Sachs disease (TSD), a fatal autosomal recessive condition most commonly found in people of Eastern European Jewish descent. Because TSD is a recessively inherited disorder, both of his cousin’s parents must have been heterozygous carriers of the mutant allele. If that is the case, Adam’s father could be a carrier as well. If Adam’s father carries the mutant TSD allele, it is possible that Adam inherited this mutation. Because Sarah is also of Eastern European Jewish ancestry, she could also be a carrier of the gene, even though no one in her family has been affected with TSD. If Adam and Sarah are both carriers, each of their children would have a 25% chance of being afflicted with TSD.

A simple blood test performed on both Sarah and Adam could determine whether they are carriers of this mutation.

Would you want to know the results of the cancer, heart disease, and TSD tests if you were Sarah and Adam? Is it their responsibility as potential parents to gather this type of information before they decide to have a child?