Scientists have discovered another piece of the genetic puzzle that may predispose humans to Crohn’s disease, a complex disorder characterised by chronic inflammation of the digestive tract. The findings may also suggest new strategies for treating this chronic, debilitating disease.
The research team tested DNA samples from patients with Crohn’s disease using the Applied Biosystems SNPlex Genotyping System, which employs predesigned assays on the company’s capillary electrophoresis DNA analysis platform. 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 ATGI6L1 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, genomewide investigation of coding SNPs,” explained Stefan Schreiber, MD, PhD, 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 etiology 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, PhD, 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.
