Download Pedigree analysis through genetics hypothesis testing

Handout
Page 1
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 2
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 The first step in genetic hypothesis testing is to understand the relationships
Page 3
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.
Autosomal recessive traits will
have the following KEY relating
genotype and phenotype
genotype
RR
Rr
rr
phenotype
unaffected
unaffected
affected
X-linked recessive traits will
have the following KEY relating
genotype and phenotype
Females
Males
genotype phenotype
genotype phenotype
RR
unaffected
RY
unaffected
Rr
unaffected
rY
affected
rr
affected
Dominant mutations will use the letter “D or d”.
D represents the mutant allele. d represents the nonmutant allele.
Autosomal dominant traits will
X-linked dominant traits will
have the following KEY relating
have the following KEY relating
genotype and phenotype
genotype and phenotype
Females
Males
genotype phenotype
genotype phenotype
genotype phenotype
DD
affected
affected
DD
DY
affected
Dd
affected
affected
Dd
dY
unaffected
dd
unaffected
unaffected
dd