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Researchers map of genetic variations implicated in disease

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The MHC Haplotype Project is creating a public resource to assist the discovery of genetic factors influencing these medical traits and to shed light on the evolution of the MHC. Access to complete sequences across several MHC haplotypes that exhibit differences in disease susceptibility will help researchers to home in on specific variants (susceptibility alleles) and to rule out regions contributing to a given disease.

Haplotypes and the MHC

Haplotypes are combinations of gene and sequence variants that tend to occur together in an individual genome. This may be purely fortuitous, or it may reflect selection of given combinations (they have been successful in the past), or it may reflect a population bottleneck, where only a few, perhaps similar, genomes have contributed to the further population growth.

The MHC is among the most gene-dense regions of the human genome and the most variable, as might be expected from a region involved in fighting infection (as well as other functions). Over evolutionary time, the MHC has been driven to become the most variable region of our genome.

The MHC Haplotype Project is studying in fine detail the sequence of eight of the most common human haplotypes, selected for conferring protection against or susceptibility to common disease. The detailed analysis of the third of these eight is reported here and compared with the two previously described.

The COX haplotype has been associated with susceptibility to a wide range of diseases, including type 1 diabetes, systemic lupus erythematosus and myasthenia gravis. The PGF haplotype provides protection against type 1 diabetes and predisposes to other diseases such as multiple sclerosis and systemic lupus erythematosus. The QBL haplotype is positively associated with Graves' disease and type 1 diabetes.


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Source:Public Library of Science


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