structuralvariant

Structural variant refers to a genomic alteration that changes the structure of the genome. In human genomics, SVs are typically defined as DNA segments larger than a small threshold, with many researchers focusing on events longer than 1 kilobase. SVs encompass deletions, duplications, insertions, inversions, translocations, and more complex rearrangements. Copy-number variants (CNVs) are a common subset representing changes in the number of copies of a genomic region.

Deletions remove sequence, duplications add copies, insertions introduce novel DNA, inversions change the orientation of a segment, and translocations relocate material to a different chromosome or position. Complex SVs may involve multiple breakpoints and rearrangements; chromothripsis is an extreme example. SVs can range from a few dozen bases to millions of bases and may be inherited or arise de novo.

Impact on phenotype and disease varies widely. SVs can alter gene dosage, disrupt coding sequences, perturb regulatory elements, or create fusion genes, contributing to developmental disorders, cancers, and susceptibility to various diseases. Many SVs are benign and contribute to normal genetic diversity.

Detection and analysis of SVs rely on array-based methods and sequencing approaches. Short-read sequencing detects SVs through discordant read pairs, split reads, and changes in coverage, but struggles with repetitive regions. Long-read sequencing improves breakpoint resolution and can resolve complex rearrangements. Computational tools integrate multiple signals to call SVs, and validation often requires orthogonal methods.

Resources and research on SVs are supported by databases such as the Database of Genomic Variants and gnomAD SV, which catalog known human SVs and their frequencies, aiding interpretation and clinical assessment.