Medical Genetics & Genomic Knowledge Flashcards

A pedigree shows an affected father who has no affected sons but all affected daughters. Which inheritance pattern is most likely?

Answer: X-linked dominant

Fathers pass their only X to all daughters and none to sons, so absent male-to-male transmission with all daughters affected indicates X-linked dominant inheritance.

Which concept best explains the variable severity of mitochondrial disease among maternally related family members?

Answer: Heteroplasmy

Heteroplasmy is the mix of mutant and normal mtDNA, and the proportion varies between cells and individuals, producing variable severity.

Approximately what percentage of individuals with Down syndrome have free trisomy 21 due to meiotic nondisjunction?

Answer: 95%

About 95% of Down syndrome cases are free trisomy 21, with the remainder due to translocations and mosaicism.

What is the most common molecular mechanism underlying Prader-Willi syndrome?

Answer: Paternal 15q11-q13 deletion

About 70% of Prader-Willi cases result from a de novo deletion of the paternally inherited 15q11-q13 region.

What CGG repeat size in FMR1 defines a full mutation associated with fragile X syndrome?

Answer: More than 200 repeats

More than 200 CGG repeats typically leads to FMR1 hypermethylation and gene silencing, causing fragile X syndrome.

Which test is most appropriate to detect a balanced reciprocal translocation in a couple with recurrent pregnancy loss?

Answer: Karyotype

Karyotype visualizes balanced rearrangements, which microarray cannot detect because there is no net gain or loss of material.

Which statement best defines penetrance?

Answer: The proportion of individuals with a disease-causing genotype who show the phenotype

Penetrance is the percentage of individuals with a given genotype who exhibit the associated phenotype, whereas expressivity refers to severity.