CGC Molecular Genetics & Mechanisms of Inheritance 2

Question 1

A splicing mutation that activates a cryptic splice site would most likely result in which of the following?

Accepted Answer

An mRNA with an additional segment of intronic sequence or deletion of exonic sequence

Answer

A protein with a single amino acid substitution

Answer

Complete absence of any mRNA transcript

Answer

Expansion of a trinucleotide repeat within the coding sequence

Question 2

Uniparental disomy (UPD) can cause disease even in the absence of a traditional mutation. Which mechanism most commonly explains pathogenicity of UPD?

Accepted Answer

Disruption of imprinted gene dosage when both copies derive from one parent

Answer

Both copies of a chromosome carry a heterozygous mutation

Answer

Mitotic recombination producing loss of heterozygosity

Answer

Replication error causing copy number variation

Question 3

Loss of heterozygosity (LOH) in tumor cells most often represents which event according to Knudson's two-hit hypothesis?

Accepted Answer

Somatic inactivation of the remaining wild-type tumor suppressor allele

Answer

Activation of an oncogene on the wild-type allele

Answer

Germline mutation in a DNA repair gene

Answer

Epigenetic silencing of an oncogene

Question 4

Which of the following correctly distinguishes an oncogene from a tumor suppressor gene regarding mechanism of cancer causation?

Accepted Answer

Oncogenes cause cancer by gain-of-function mutations acting dominantly; tumor suppressors cause cancer when both alleles are inactivated (recessive)

Answer

Oncogenes require loss of both alleles; tumor suppressors require gain of function in one allele

Answer

Oncogenes are only activated by chromosomal translocations; tumor suppressors are only inactivated by point mutations

Answer

Oncogenes and tumor suppressors are functionally identical but differ in chromosomal location

Question 5

X-inactivation (lyonization) in females results in which of the following outcomes relevant to X-linked carrier females?

Accepted Answer

Random inactivation of one X per cell that becomes fixed clonally, potentially leading to skewed X-inactivation in some tissues

Answer

Equal expression of both X chromosomes in all cells throughout life

Answer

Preferential inactivation of the paternally derived X chromosome in all somatic cells

Answer

Complete inactivation of both X chromosomes leaving no X gene expression

Question 6

A copy number variant (CNV) is best defined as:

Accepted Answer

A structural variation involving a segment of DNA ≥1 kb that differs in copy number between individuals

Answer

A single nucleotide change that alters a codon's amino acid

Answer

A trinucleotide repeat expansion beyond the normal range

Answer

An epigenetic modification that alters gene expression without changing sequence

Question 7

Which inheritance pattern is characterized by mitochondrial DNA mutations transmitting exclusively through the maternal line with all offspring of an affected mother being at risk?

Accepted Answer

Mitochondrial (maternal) inheritance

Answer

Autosomal dominant inheritance

Answer

X-linked dominant inheritance

Answer

Autosomal recessive inheritance