ABMGG Molecular Genetics and Genomics Techniques Flashcards

Which next-generation sequencing approach sequences all protein-coding regions of the genome and is commonly used in ABMGG clinical practice?

Answer: Whole exome sequencing

Whole exome sequencing targets the ~1–2% of the genome that encodes proteins and is a primary clinical tool for diagnosing rare Mendelian disorders.

What is the primary purpose of chromosomal microarray analysis (CMA) in medical genetics?

Answer: Detecting copy number variants across the genome

CMA detects submicroscopic deletions and duplications (copy number variants) that are below the resolution of conventional karyotyping.

Which molecular technique is the gold standard for confirming the size of trinucleotide repeat expansions such as those in Huntington disease?

Answer: Southern blot analysis

Southern blot can accurately size large repeat expansions that PCR-based methods may fail to amplify through, making it the confirmatory standard.

In ABMGG genomic practice, a variant of uncertain significance (VUS) is best managed by:

Answer: Performing segregation analysis in affected family members

Segregation analysis—checking whether the VUS cosegregates with disease in family members—is the primary strategy to reclassify a VUS toward pathogenic or benign.

Which bioinformatics database is most commonly used by ABMGG-certified clinical laboratory geneticists to interpret variant pathogenicity?

Answer: ClinVar

ClinVar is the NIH-hosted repository of variant–disease interpretations submitted by clinical laboratories and is integral to ACMG/AMP variant classification guidelines.

The ACMG/AMP 2015 framework classifies sequence variants into how many categories?

Answer: 5

The five categories are: pathogenic, likely pathogenic, uncertain significance, likely benign, and benign.