Nonallelic

Nonallelic is an adjective used in genetics to describe loci or sequences that are not alleles of the same gene at a single chromosomal position. In other words, nonallelic loci are at different positions in the genome but may share substantial sequence similarity, often because they originated from gene duplications. The term is most commonly encountered in discussions of nonallelic homologous recombination (NAHR), a misalignment event during meiosis in which recombination occurs between similar sequences at non-allelic positions rather than between true alleles.

Nonallelic homologous recombination can generate structural variations in the genome, including deletions, duplications, inversions, and, less frequently, translocations. These rearrangements often involve segmental duplications or low-copy repeats that flank a genomic region, promoting recurrent rearrangements with similar breakpoints. NAHR is a major mechanism underlying several well-characterized genetic disorders and contributes to genomic instability.

Examples of NAHR-related disorders include duplication of the PMP22 gene on chromosome 17p12, which causes Charcot–Marie–Tooth disease type 1A, and deletions at 22q11.2, which underlie velocardiofacial/DiGeorge syndrome. The nonallelic nature of the recombining sequences explains why these conditions arise repeatedly in different individuals and why the affected regions exhibit recurrent rearrangements.

Understanding nonallelic processes helps explain certain patterns of genetic disease and contributes to approaches in diagnosis, counseling, and studies of genome evolution.