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Dartmouth researchers discover gene signatures for scleroderma
Date:7/15/2008

"Since no one understands the basic processes that cause scleroderma, it has been largely categorized by the distribution of clinical findings, such as the location of skin thickening (torso relative to the hands). These studies, utilizing objective measures, establish that distinct genetic programs account for the ways this disease manifests itself and hold out the possibility for an improved ability to treat and induce remission of this potentially fatal disease," adds Rigby, who is a professor of medicine and of microbiology and immunology.

The work continues a longtime collaboration with Dr. Kari Connolly at the University of California, San Francisco, which has a large scleroderma patient population. It builds on a map of skin that Whitfield and colleagues created using gene expression -- which genes are turned on-- to delineate differences among scleroderma patients beyond obvious symptoms.

The map was based on skin samples from patients with diffuse scleroderma, the most severe form of the disease, and healthy controls. Two skin samples were taken from each patient: one from affected skin in the forearm, and another from an unaffected lower back area, which though seemingly healthy, also showed aberrant genes, demonstrating the disease was truly systemic when the biopsies were taken.

The new research is considered the largest scleroderma gene expression study to date. The investigators analyzed gene activity in 28 patients with varying types of scleroderma and six healthy control subjects, using skin biopsies from an arm and back.

Whitfield compares the molecular classification to how breast and other cancers have been characterized. "Our goal was to go into a disease of completely different etiology, but plagued by similar problems of clinical heterogeneity and to quantify disease subsets at the gene expression level."

The researchers used DNA mircoarrays to measure gene expression and computational alg
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Contact: Hali Wickner
hali.wickner@dartmouth.edu
Dartmouth Medical School
Source:Eurekalert

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