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U-M scientists identify major psoriasis susceptibility gene

ine which gene in the MHC was involved in psoriasis."

In a previous study, Nair and his U-M colleagues narrowed the search for the PSORS1 gene down to a 300,000-base-pair segment of chromosome 6 that included HLA-C and at least 10 other genes.

To determine which of the 11 genes was linked to psoriasis, U-M scientists used a technique called haplotype mapping. Haplotypes are clusters of alleles that tend to be inherited together as a group, because they are located close to each other on the same chromosome. This means that small individual variations in DNA, which originated in a distant ancestor, are often passed intact from generation to generation. If a haplotype contains genetic changes that make people more susceptible to a disease, scientists can find it by comparing DNA sequences in haplotypes from people with the disease to those of people who don't have the disease.

U-M researchers first sequenced and compared all DNA within the 300,000 base-pair target segment from 10 MHC chromosomes carried by five people enrolled in the study. Detailed analysis of these 10 DNA sequences revealed differences that were only present on psoriasis chromosomes, but never on normal chromosomes. Further analysis by U-M scientists narrowed the search down to one gene, HLA-C, and one specific disease-causing allele, HLA-Cw6.

Drugs used to treat psoriasis are also used for other autoimmune diseases, such as lupus and rheumatoid arthritis. These drugs turn off the immune response, which leaves the body vulnerable to infection. Now that U-M scientists have identified HLA-Cw6 as being the PSORS1 gene, Elder says scientists can concentrate on finding ways to block its ability to bind to cell surface antigens, which could lead to the development of safer treatments for psoriasis.

"What we're all shooting for is trying to find out which branches of the immune system are triggering psoriasis, so you don't have to shut down the whole immune system
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Source:University of Michigan Health System


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