referencegenome

A reference genome is a digital sequence that serves as a standard or baseline for a species’ genomic DNA. It provides a common coordinate system and annotation framework for aligning sequencing reads, identifying variants, and interpreting gene structure and function. A reference is not the genome of a single individual; it is typically a mosaic assembled from multiple individuals, with additional sequences sometimes derived from specialized cell lines or long-read data.

Construction and maintenance of a reference genome involve assembling and scaffolding reads into a contiguous sequence, filling gaps where possible, and annotating genes, regulatory elements, and other features. Early references were linear and haploid representations of a paternal or maternal haplotype, but modern builds often include alternate loci and decoy sequences to represent common structural variation and to reduce misalignment. Reference versions are periodically updated or replaced, leading to new genome builds with standardized coordinates and liftover tools to translate annotations and data between versions.

Uses of a reference genome include guiding read alignment, variant discovery and genotyping, and functional annotation of genes and regulatory regions. They enable cross-study comparisons and integration with public databases. Limitations include reference bias, where reads derived from non-reference alleles align less efficiently, and underrepresentation of genetic diversity from non-European populations in some species. As sequencing data and methods advance, alternative representations such as graph genomes and pangenomes are being explored to capture broader diversity beyond a single linear reference.