structuralvariation

Structural variation refers to genomic alterations that involve segments of DNA typically larger than 50 base pairs and that differ among individuals or populations. It encompasses deletions, duplications, insertions, inversions, translocations, and more complex rearrangements, including multi-allelic copy number variations. These variants can affect single genes, multiple genes, regulatory elements, or broader chromosomal contexts.

Structural variants arise through diverse mechanisms, including non-allelic homologous recombination, replication-based errors, and mobile element activity. They contribute to normal genetic diversity but can also disrupt gene function, alter gene dosage, or rearrange regulatory landscapes, contributing to developmental disorders, neuropsychiatric conditions, and cancer.

Detection and study of structural variation rely on sequencing and genotyping technologies. Short-read sequencing and microarrays can detect many SVs via changes in read depth, paired-end orientation, or split reads, though complex variants are often challenging to resolve. Long-read sequencing (PacBio, Oxford Nanopore) and linked-read approaches improve breakpoint precision and haplotype phasing. Large projects such as the 1000 Genomes Project and gnomAD SV provide population-level resources, while clinical databases (e.g., DGV, DECIPHER) document observed SVs and help with interpretation.

Structural variation remains an active field, with ongoing efforts to refine discovery methods, integrate SV data with single-nucleotide variation, and translate findings into clinical insights.