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News Release from: Applied Biosystems | Subject: SNPlex Genotyping System
Edited by the Laboratorytalk Editorial
Team on 31 January 2007
Discovery of gene associated with
Crohn's Disease
Applied Biosystems genotyping technologies uncover new support for role of abnormal immune response to intestinal bacteria in the disease
Scientists have discovered another piece of the genetic puzzle that may predispose humans to Crohn's disease, a complex disorder characterized by chronic inflammation of the digestive tract The findings may also suggest new strategies for treating this chronic, debilitating disease
This article was originally published on Laboratorytalk on 7 Dec 2007 at 8.00am (UK)
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Researchers from the University Hospital of the Christian-Albrechts University in Kiel, Germany and Applied Biosystems have identified and characterised a novel genetic variation in a gene not previously associated with the disorder that provides further evidence that an abnormal immune response to bacteria in the digestive tract may lead to the intestinal inflammation characteristic of the disease.
The results of the team's three-year collaboration will be published in the February issue of Nature Genetics.
The research team tested DNA samples from patients with Crohn's disease using the Applied Biosystems SNPlex genotyping system, which employs pre-designed assays on the company's capillary electrophoresis DNA analysis platform.
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As part of the genotyping study, the team conducted a genome-wide association scan of approximately 20,000 'coding' genetic variants that are thought to produce functional changes at the protein level.
Among their findings, the researchers identified a protein-coding genetic variation (a single nucleotide polymorphism, or SNP) in the autophagy-related 16-like (ATG16L1) gene.
Neither the ATG16L1 gene, nor this specific genetic variation, has been previously implicated in Crohn's disease.
The ATGI6LI gene is part of the autophagosome biological pathway, which normal cells use to destroy harmful bacteria.
"With the discovery of APG16L1 as a new gene associated with Crohn's disease, we have demonstrated the power of a targeted, genome-wide investigation of coding SNPs," said Stefan Schreiber, professor of medicine at the Christian-Albrechts University in Kiel, Germany, and senior author of the study.
"We also have discovered a further piece of evidence that highlights epithelial cells in the digestive tract and therefore a weakened barrier function as the most likely target for the underlying aetiology of chronic inflammatory bowel disease".
"With further evidence that genetic factors may be compromising the defences of the intestinal barrier in Crohn's disease, we believe pharmaceutical researchers have an opportunity to design new therapies that may address the root cause, not just the symptoms, of this chronic disease," added Francisco De La Vega, scientific fellow, Applied Biosystems, and a co-author of paper.
"We plan to continue using this targeted approach with coding SNPs to study this and other complex diseases".
Applied Biosystems is providing access to the list of SNPs selected for this study via its website.
Researchers can browse the SNP data and link to pre-designed assays for each genetic variation of interest.
Over 3000 of these SNPs were not previously available in the public domain and were discovered in the gene re-sequencing efforts of the Applera Genomics Initiative.
As part of this publication, these novel variants also will be deposited in the NCBI's dbSNP database under submission handle ABI for perusal by the scientific community in other targeted association studies.
The study was selected by the editors of Nature Genetics for advance online publication and is available now to the journal's subscribers.
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