Laboratory and Genomic Testing
Test selection and interpretation
Know the main modalities: karyotype (large structural changes, aneuploidy), chromosomal microarray (copy-number variants, first-tier for developmental delay), targeted sequencing, gene panels, exome and genome sequencing, and methylation or repeat-expansion tests for specific disorders. Each has resolution limits and blind spots: karyotype misses small deletions, microarray misses balanced rearrangements and point mutations, and exome sequencing misses deep intronic and some structural variants.
Variant classification
Candidates must understand the ACMG/AMP framework in principle: pathogenic, likely pathogenic, uncertain significance, likely benign, benign, based on evidence such as population frequency, computational prediction, functional data, segregation, and de novo occurrence. A VUS is not a normal result and not a diagnosis; it is managed with periodic reclassification review.
Traps
Questions test confusing a negative result with absence of disease, misreading analytic sensitivity versus clinical sensitivity, and forgetting that variant interpretation depends on the lab's evidence and can change. Also watch for conflating screening and diagnostic platforms, and for assuming all labs report the same variants identically. Confirmatory testing may be needed for research or direct-to-consumer results before clinical action.
Rule of thumb
Match the test to the question: suspected aneuploidy, use karyotype or microarray; suspected single-gene disorder, use targeted or panel testing; undiagnosed multisystem disease, consider exome or genome. Example: a child with developmental delay and dysmorphism should first receive chromosomal microarray, not a single-gene test, because copy-number changes are common and broad.