ABMGG ABMGG Molecular Genetics and Genomics Techniques 1 — Questions and Answers
Question 1: Which next-generation sequencing approach sequences all protein-coding regions of the genome and is commonly used in ABMGG clinical practice?
- Whole exome sequencing (Correct answer)
- RNA sequencing
- Methylation array
- Chromosomal microarray
Correct 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.
Question 2: What is the primary purpose of chromosomal microarray analysis (CMA) in medical genetics?
- Detecting copy number variants across the genome (Correct answer)
- Sequencing individual gene exons
- Measuring RNA expression levels
- Identifying trinucleotide repeat expansions
Correct 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.
Question 3: Which molecular technique is the gold standard for confirming the size of trinucleotide repeat expansions such as those in Huntington disease?
- Southern blot analysis (Correct answer)
- FISH
- Chromosomal microarray
- Whole genome sequencing
Correct 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.
Question 4: In ABMGG genomic practice, a variant of uncertain significance (VUS) is best managed by:
- Performing segregation analysis in affected family members (Correct answer)
- Immediately reporting it as pathogenic to the ordering clinician
- Ignoring it because it has no clinical significance
- Treating the patient based on the VUS alone
Correct 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.
Question 5: Which bioinformatics database is most commonly used by ABMGG-certified clinical laboratory geneticists to interpret variant pathogenicity?
- ClinVar (Correct answer)
- PubMed
- OMIM only
- GenBank
Correct 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.
Question 6: The ACMG/AMP 2015 framework classifies sequence variants into how many categories?
- 5 (Correct answer)
- 3
- 7
- 4
Correct answer: 5
The five categories are: pathogenic, likely pathogenic, uncertain significance, likely benign, and benign.
ABMGG ABMGG Molecular Genetics and Genomics Techniques 1
Which next-generation sequencing approach sequences all protein-coding regions of the genome and is commonly used in ABMGG clinical practice?