Huntington’s disease is a rare autosomal dominant trait (lethal in the homozygous dominant condition). The mutation is an expansion of a nucleotide repeat in the DNA that encodes the huntingtin protein. Normal individuals have between 6-35 copies of a CAG repeat within the gene. Affected individuals can have between 36-121 repeats. In aIDition, as the number of repeated triplets (CAG) increases, the age of onset in the patient decreases. Individuals with this disease suffer from progressive neurodegeneration eventually resulting in death.
a. A 20-year old single woman whose father died of Huntington’s disease is concerned about her risk of eventually developing the disease. What is the probability that she will eventually get HD, if her mother is phenotypically normal?
b. The HD gene has been sequenced and its location on chromosome 4 has been well characterized. The entire DNA sequence of chromosome 4 has been sequenced. A genetic screen can definitively determine whether this woman has the HD mutant allele.
i. What reaction components would be needed to PCR amplify the HD alleles from her genome?
ii. Once the alleles were amplified, how could you compare the size of her alleles to alleles from other individuals?
iii. If this woman was heterozygous at the HD locus, describe the sizes of the two PCR-amplified alleles and how they would compare to amplified alleles from both of her parents.
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