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Scientists find new genes for Crohn's disease

owever, mutations in these two genes alone cannot account for the entire genetic component of the disease. To identify additional genes that are associated with Crohn's, the researchers scanned more than 300,000 single nucleotide polymorphisms, or SNPs, in the genomes—all of 22,000 or so genes—in people with Crohn's disease and in healthy controls. SNPs are subtle variations in the genetic code found in all genes. Some variations can be harmful, while others may be helpful or have no effect at all.

The comparison of these SNPs between patients with Crohn's disease and people without the disease identified multiple variations in several genes that were strongly associated with Crohn's disease. These findings were then retested in two additional sets of patients and healthy controls in order to confirm their significance. After all of the comparisons, the consortium identified variations in three genes ?PHOX2B, NCF4 and ATG16L1 ?as contributing significantly to the risk for Crohn's disease.

According to corresponding author John D. Rioux, Ph.D., associate professor of medicine at the Montreal Heart Institute and at the Université de Montréal, the identification of the PHOX2B gene in this study suggests that neuroendocrine cells of the intestinal epithelium have a key role to play in Crohn's. In addition, the identification of the NCF4 gene indicates that the production of altered reactive oxygen species, which are important in the generation of a protective response against microbes, may lead to an increased risk of developing the condition.

Particularly interesting to the authors was the association between Crohn's and variations in the ATG16L1 gene, which they found is essential for the cell's normal mechanism for degrading worn-out cellular components and helping to eliminate some pathogenic bacteria—a pathway known as autophagy (pronounced AU-TOF-A-GEE ).

Finding ATG16L1's involvement in Crohn's disease provides confirmat
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Source:University of Pittsburgh Schools of the Health Sciences


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