Pedigrees A and B both 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. Handout Page 1

Individuals 11 and 12 are concerned because 11 is pregnant with their third child. They just learned that their daughter also has cancer, has both mutations, and they are worried about their next child. How can you determine the chance of that third child inheriting both mutations? To determine the chance that 11 and 12’s third child will inherit both mutations, it is necessary to determine the mode of inheritance of each trait. Are they inherited as dominant or recessive traits? Are the genes autosomal or X-linked? To determine the answers, you can engage in genetic hypothesis testing. 1.Make a hypothesis that the trait is inherited according to a particular mechanism (for example autosomal recessive). 2.Determine whether the pattern of inheritance observed in the family is consistent with the predictions of that hypothesis. 3.Reject the hypothesis if the observed phenotypes of the offspring do not match the phenotypes predicted by the hypothesis. 4.Remember that observed phenotypes that are consistent with predictions do not ‘prove’ that hypothesis to be correct, but rather just fails to reject the hypothesis. Observations from other families in the pedigree can reinforce the support for a hypothesis and provide very strong support if all other hypotheses have been rejected. Handout Page 2

The first step in genetic hypothesis testing is to understand the relationships between genotypes and phenotypes using symbols for alleles. Recessive mutations use the letter “R or r”. R represents the nonmutant allele. r represents the mutant allele. genotype RR Rr rr phenotype unaffected affected Autosomal recessive traits will have the following KEY relating genotype and phenotype X-linked recessive traits will have the following KEY relating genotype and phenotype phenotype unaffected affected genotype RR Rr rr Females phenotype unaffected affected genotype RY rY Males Dominant mutations will use the letter “D or d”. D represents the mutant allele. d represents the nonmutant allele. genotype DD Dd dd phenotype affected unaffected Autosomal dominant traits will have the following KEY relating genotype and phenotype X-linked dominant traits will have the following KEY relating genotype and phenotype phenotype affected unaffected genotype DD Dd dd Females phenotype affected unaffected genotype DY dY Males Handout Page 3