Structural Variants: Mechanisms, Mapping, and Interpretation in Human Genetics

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an overview of structural variations, their mutagenesis mechanisms, and their detection in the genomics era, focusing on the biological significance, methodologies, and future directions in the field.