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Researchers map of genetic variations implicated in disease

Sequence differences in less than 0.2% of the 3-billion-base human genome play a vital role in a bewildering variety of human disease. Today, researchers from the Wellcome Trust Sanger Institute and the Cambridge University's Cambridge Institute for Medical Research, together with international colleagues report in PLoS Genetics their detailed maps of differences implicated in disease as well as genes that are unchanged in recent human history.

The Major Histocompatibility Complex (MHC) consists of hundreds of genes on human chromosome 6 that are important in most autoimmune conditions, when our biological defences turn on our own systems. The MHC has the major role in type 1 diabetes and rheumatoid arthritis. The MHC is also pivotal in response to infection, including malaria and AIDS.

Genes in the MHC can differ dramatically between people, and the differences among us affect medical events as diverse as tissue transplant rejection, arthritis, asthma and disease resistance. A detailed study of this region in different people will shed light on which genes are most important.

"We analysed the entire MHC region in detail from three individuals that carried different susceptibility to disease," explained Dr Stephan Beck, leader of the team at the Wellcome Trust Sanger Institute. Key differences were then further analysed in a much larger population of 140 DNA samples.

"Within the sea of over 20,000 sequence variations across the 4 million MHC bases, we found one island of stability," continued Dr Beck. "A region of 160,000 bases that is up to 200-fold less variant between chromosomes sharing part of the same HLA type, suggesting these individuals most likely shared a common ancestor as recently as 50,000 years ago."

Swapping of ancestral sequence blocks is a potential mechanism (identity-by-descent) whereby certain gene combinations, which presumably have favoured immunological advantage (e.g. resistance to infectious disea
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Source:Public Library of Science


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