Cambridge Reference Sequence

The Cambridge Reference Sequence (CRS) for human mitochondrial DNA was first published in 1981 leading to the initiation of the human genome project.

A group under Dr. Fred Sanger at Cambridge University sequenced the mitochondrial genome of one individual of European descent during the 1970s, determining it to have a length of 16,569 base pairs (0.0006% of the total human genome) containing some 37 genes.

When other researchers repeated the sequencing, some striking discrepancies were noted. The original published sequence included eleven errors, including one extra base pair in position 3107, and incorrect assignments of single base pairs. Some of these were the result of contamination with bovine and HeLa specimens. The corrected revised CRS was published by Andrews et al. in 1999. (The original nucleotide numbering was retained to avoid confusion.) The reference sequence belongs to European haplogroup H2a2a. The revised CRS is designated as rCRS.

When mitochondrial DNA sequencing is used for genealogical purposes, the results are usually reported as differences from the revised CRS. Such differences are not necessarily mutations: the CRS is a reference sequence rather than a record of the earliest human mtDNA. A difference from the CRS may represent a nucleotide that was ancestral to the haplotype of the CRS, which would mean that the mutation occurred in the CRS reference specimen rather than the tested specimen, or may represent an actual mutation.

External links

• GenBank record of the revised Cambridge Reference Sequence (rCRS)
• An annotated revised Cambridge Reference Sequence (rCRS) at PhyloTree.org