Reference genome

A reference genome (also known as a reference assembly) is a digital nucleic acid sequence database, assembled by scientists as a representative example of a species' genetic code. As they are often assembled from the sequencing of DNA from a number of donors, reference genomes do not accurately represent the genetic code of any single individual. Instead a reference provides a haploid mosaic of different DNA sequences from each donor. For example GRCh37, the Genome Reference Consortium human genome (build 37) is derived from thirteen anonymous volunteers from Buffalo, New York. The ABO blood group system differs among humans, but the human reference genome contains only an O allele (although the other alleles are annotated).

As the cost of DNA sequencing falls, and new full genome sequencing technologies emerge, more genome sequences continue to be generated. Reference genomes are typically used as a guide on which new genomes are built, enabling them to be assembled much more quickly and cheaply than the initial Human Genome Project. Most individuals with their entire genome sequenced, such as James D. Watson, had their genome assembled in this manner. For much of a genome, the reference provides a good approximation of the DNA of any single individual. But in regions with high allelic diversity, such as the major histocompatibility complex in humans and the major urinary proteins of mice, the reference genome may differ significantly from other individuals. Comparison between the reference (build 36) and Watson's genome revealed 3.3 million single nucleotide polymorphism differences, while about 1.4 percent of his DNA could not be matched to the reference genome at all. For regions where there is known to be large scale variation, sets of alternate loci are assembled alongside the reference locus.

The human and mouse reference genomes are maintained and improved by the Genome Reference Consortium (GRC), a group of less than 20 scientists from a number of genome research institutes, including the European Bioinformatics Institute, the National Center for Biotechnology Information, The Sanger Institute and Washington University in St. Louis. GRC continues to improve reference genomes by building new alignments that contain fewer gaps, and fixing misrepresentations in the sequence. As of 2010, the human reference genome is in its 19th version. The GRCh37 build contains around 250 gaps, whereas the first version had ~150,000 gaps.

Reference genomes can be accessed online at several locations, using dedicated browsers such as Ensembl or UCSC Genome Browser.