ABMGG Molecular Genetics and Genomics Techniques Flashcards

What does fluorescence in situ hybridization (FISH) detect that a standard G-banded karyotype typically cannot?

Answer: Submicroscopic deletions at specific loci

FISH uses labeled probes to detect deletions or duplications at targeted loci below the ~5–10 Mb resolution of conventional karyotyping.

Which sequencing methodology is used to detect epigenetic modifications such as DNA methylation patterns relevant to imprinting disorders?

Answer: Bisulfite sequencing

Bisulfite treatment converts unmethylated cytosines to uracil while leaving methylated cytosines intact, enabling methylation mapping by sequencing.

RNA sequencing (RNA-seq) adds clinical value in medical genetics primarily by:

Answer: Identifying splicing defects and allele-specific expression abnormalities

RNA-seq can reveal aberrant splicing caused by deep intronic variants and confirm whether a variant affects gene expression, increasing diagnostic yield.

In the context of ABMGG laboratory practice, what is a mosaic variant?

Answer: A variant present in only a subset of an individual's cells

Mosaicism arises when a post-zygotic mutation occurs in a progenitor cell, resulting in two or more genetically distinct cell populations within the same individual.

Which term describes a variant that arose newly in a patient and is not present in either biological parent?

Answer: De novo variant

A de novo variant occurs as a new mutation in the proband and is confirmed by demonstrating its absence in both parents via trio sequencing or targeted testing.

Long-read sequencing technologies (e.g., PacBio, Oxford Nanopore) offer a key advantage over short-read platforms for clinical genomics because they:

Answer: Can span repetitive regions and resolve complex structural variants

Long reads can traverse repetitive DNA, phasing variants and characterizing structural rearrangements that short reads cannot span.