hotspotsvariants

Hotspotsvariants is a term used in genetics to describe genetic variants that occur disproportionately at mutational hotspots in the genome. A hotspot is a locality where the rate of mutation is higher than the surrounding sequence, leading to recurrent variants that appear in multiple individuals or tumor samples.

Several molecular mechanisms contribute to hotspots: chemically reactive motifs such as methylated CpG dinucleotides, which frequently mutate to thymine; sequence context that impairs proofreading; replication stress; and defects in DNA repair pathways. In cancer genomes, hotspots are common in known driver genes and may reflect positive selection for advantageous changes.

Identification of hotspotsvariants relies on large-scale sequencing data and careful statistical modeling. Analysts compare observed recurrence of a variant to a background mutation rate that accounts for base context, trinucleotide context, and sequencing depth. Methods must distinguish true biological recurrence from technical artifacts and sampling bias.

Applications include mapping mutational processes, improving models of disease risk, and guiding interpretations of sequencing results in clinical genomics. Hotspotsvariants help prioritize variants for functional follow-up and can inform studies of population history and somatic evolution.

Limitations include distinguishing causative recurrent variants from hitchhiking passengers, mitigating biases from uneven sampling, and interpreting context-dependent effects across tissues. Ongoing work seeks standardized definitions and analytic frameworks to compare hotspotsvariants across studies.