HLA A1-B8-DR3-DQ2

HLA A1-B8-DR3-DQ2 haplotype (Also: AH8.1, COX, Super B8, ancestral MHC 8.1 or 8.1 ancestral haplotype) is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6 (not to be confused with the HLA-DQ heterodimer DQ8.1). A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of descent by common ancestry (share a recent common ancestor for that segment of the chromosome). Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

The haplotype can be written in an extended form covering the major histocompatibility loci as follows:

HLA A*0101 : Cw*0701 : B*0801 : DRB1*0301 : DQA1*0501 : DQB1*0201 or shorthand A1::DQ2

There are many other gene-alleles within the haplotype, including more than 250 coding loci that produce transcripts.

At 4.7 million nucleotides in length, A1::DQ2 is the second longest haplotype identified within the human genome. A1::DQ2 creates a conundrum for the evolutionary study of recombination. The length of the haplotype is remarkable because of the rapid rate of evolution at the HLA locus should degrade such long haplotypes. A1::DQ2's origin is difficult to trace, suggestions of a common ancestor in Iberia or Africa have been put forward. Although its place of origin is not certain there is agreement that bearers of the European AH8.1 bear a haplotype related by a common descent. A1::DQ2 is the most frequent haplotype of its length found in US Caucasians, ~15% carry this common haplotype.

Studies indicate that A1::DQ2 prominence is likely due to positive selection in the pre-Neolithic period and isolation in countries where wheat was not a prominent cereal. Outside of DR3-DQ2 with known associations to autoimmune disease, other factors within A1::DQ2 are believed to also contribute to autoimmune disease. Also a dozen inflammatory diseases of the immune system can attribute some risk to the haplotype. Some disease like coeliac disease primarily associate with certain genes. While other diseases, like type 1 diabetes may have several, highly different, genes that attribute risk. Still other diseases, like myasthenia gravis have undetermined linkage to the haplotype.