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The Cambridge Reference Sequence (CRS) for human mitochondrial DNA was first published in 1981 as a forerunner of the human genome project. It should be noted that sometimes the abbreviation "CRS" is used to mean "coding region sequence" with regard to mitochondrial DNA. This should not be confused with the Cambridge Reference Sequence, which omits the coding region for reference entirely and instead only accounts for the Hypervariable regions or HVRs.
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 about 16,568 base pairs (0.0006% of the total human genome) containing some 37 genes.
When the sequencing was repeated by other researchers, it was noted that there were some striking discrepancies. On further replication, it was determined that the original publication had included some eleven errors of sequencing, including one "extra" base pair in position 3,107, and occasional incorrect assignments of single base pairs. Some of these were the result of contamination with bovine and HeLa specimens. The revised CRS mtDNA was published by Richard Andrews in 1999. (The original nucleotide numbering was retained to avoid confusion.) The reference sequence belongs to European haplogroup H.
When mitochondrial DNA testing 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.
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