ABMGG LGG cheat sheet

Mitotic metaphase chromosome count in humans is 46; aneuploidy is any count other than an exact multiple of 23, while polyploidy is a whole-set multiple such as 69,XXX.

Standard G-banded karyotype resolution is ~400-550 bands per haploid set; each band averages ~5-10 Mb, so rearrangements below this size require FISH, CMA, or sequencing.

Chromosomal microarray detects copy-number changes (deletions/duplications) but is blind to balanced rearrangements, most point variants, and copy-neutral loss of heterozygosity unless SNP probes are included.

For a constitutional triploidy or maternal-cell-contamination concern, quantitative fluorescence PCR or STR genotyping compares parental and fetal allele ratios rather than relying on band counts alone.

Sanger sequencing detects single-nucleotide variants and small indels with a limit of detection near 15-20% variant allele fraction; below that, deep NGS or digital PCR is required.

Next-generation sequencing analytic sensitivity depends on depth: ~30x germline whole-genome and ~100x+ for somatic panels; orthogonal confirmation is required for reportable pathogenic variants.

Deletion/duplication testing by MLPA or targeted exon-level CMA is the first-tier assay when a single-gene disorder is suspected and the causative mechanism is a whole-exon loss.

A variant is classified per ACMG/AMP five-tier framework (pathogenic, likely pathogenic, VUS, likely benign, benign); VUS results are not reported as causative without segregation or functional evidence.

Autosomal dominant inheritance: one affected parent gives 50% recurrence risk per offspring; variable expressivity and incomplete penetrance can mask the family history.

Autosomal recessive inheritance: two carrier parents give 25% affected, 50% carrier, 25% unaffected; consanguinity raises carrier-match probability.

X-linked recessive: carrier females are usually unaffected; affected males transmit the allele to all daughters (obligate carriers) and no sons.

Mitochondrial inheritance: transmitted through the maternal line only; heteroplasmy explains variable severity, and recurrence risk to offspring of an affected female approaches 100% for the allele, not the phenotype.

Trisomy 21 recurrence risk after a prior affected pregnancy is ~1% (or higher with parental translocation); maternal age is the strongest single risk factor.

Newborn screening is a public-health program with disorder-specific sensitivity/specificity; a positive screen is presumptive and requires confirmatory diagnostic testing.

Prenatal screening (maternal serum analytes, cell-free DNA) estimates risk and is not diagnostic; diagnostic testing requires chorionic villus sampling or amniocentesis.

Genetic counseling follows a risk-assessment-to-informed-decision model: pedigree, risk calculation, test options, and documentation of the patient's autonomous choice.