Describe two mechanisms for causing uniparental disomy, and explain how this chromosomal defect is involved in Prader-Willi syndrome and Angelman syndrome

Question

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Answer 1

Uniparental disomy occurs when both copies of a homologous chromosome pair originate from a single parent. Uniparental disomy has two mechanisms of origin. First, the rare mechanism would involve nondisjunction of the same chromosome in both the sperm and egg. Second, the more common mechanism involves nondisjunction in one parent that creates an aneuploid gamete contributing two copies of chromosome 15. The other gamete is normal and contributes a single copy of chromosome 15. Gamete union results in trisomy 15, but through the process of trisomy rescue, one of the extra copies of chromosome 15 is randomly ejected in one of the first mitotic divisions following fertilization. This results in a zygote that retains two copies of chromosome 15 from the same parent (i.e., uniparental disomy).
Both Angelman syndrome and Prader-Willi syndrome are usually the result of a partial deletion of the 15q11.12 portion of chromosome 15. Uniparental disomy produces 10-20% of cases of AS and PWS. When uniparental disomy causes AS, both copies of chromosome 15 are from the father, and there is no maternal copy of chromosome 15. In uniparental disomy cases of PWS, both copies of chromosome 15 are from the mother, and there is no copy of the paternal chromosome 15.