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Researchers map of genetic variations implicated in disease

se), can spread across haplotypes and populations.

Professor John Trowsdale, at the Department of Pathology, University of Cambridge, said, "The region, called DR-DQ, where we find this island of stability is one of the most variable in our genome, yet in some people it has been 'fixed'. We suggest that ancestral DR-DQ blocks have been shuffled into different MHC backgrounds and subsequently expanded in frequency across European populations.

"These 'fixed' haplotypes might then have expanded because they protected against infection and disease. We hope to show, in further studies, whether this stable region was a key to disease resistance in our recent past."

The study further described over 300 amino acid changing variants in gene sequences. These variants are strong candidates for functional studies to understand the role of variation in MHC-associated disease.

Autoimmune disease affects about 3 million people in the UK. The three haplotypes studied here display different susceptibilities to diseases such as type 1 diabetes, myasthenia gravis and multiple sclerosis.

For some common autoimmune diseases the MHC provides by far the largest genetic contribution by a single chromosome region. For example, the MHC accounts for at least 30% of the familial aggregation in type 1 diabetes and rheumatoid arthritis.

"Data generated by projects such as the MHC Haplotype Project will feed into the recently announced Wellcome Trust Case-Control Consortium," explained Professor John Todd, Professor of Medical Genetics at the Cambridge Institute for Medical Research, "and the WTCCC search for the genetic signposts for eight common diseases will be accelerated by the new markers reported here. At an ever increasing rate, we are developing the necessary tools and sample collections to make a real difference to the study, diagnosis and, we hope, treatment of diseases such as TB, coronary heart disease, diabetes and rheumatoid arthrit
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Source:Public Library of Science


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