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11-12-2011 | Genetics | Article

Gene mapping allows further insights into Crohn’s disease genetics


Free abstract

MedWire News: Scientists have identified three further genes on chromosome 16 - CYLD, IRF8, and CDH1/CDH3 - associated with Crohn's disease (CD).

This finding adds to previous research pinpointing the gene NOD2 as a causative locus for the condition, and may help explain the particularly strong association with CD seen on chromosome 16q.

The team, lead by Nikolas Maniatis (University College London, UK), used a genetic mapping approach on genome-wide CD association data collected by the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases to try and identify additional genetic regions associated with CD on chromosome 16.

Rather than searching for a causal variant using one single-nucleotide polymorphism (SNP) assumed to be in strong LD with the causal variant, this approach utilized multiple SNPs within the chromosome 16q genomic region around NOD2 to estimate the most likely causal location by taking into account the structure of LD in the human genome.

Maniatis commented: "This project essentially maps the most likely location of faulty sites for CD in the genome. By combining several pieces of information together, our technique lets us increase the power of our analysis."

The multimarker genetic mapping technique identified the genes CYLD, IRF8, and CDH1/CDH3 as being associated with CD. These genes are known to be involved with immune dysregulation and inflammation in the body.

"These are very exciting times, as we can use these genetic maps to pinpoint where the causal sites of CD are located," said Maniatis.

"Although it has been shown in the past that a proportion of patients suffering from CD do not carry the NOD2 mutations, up until now no other genes on chromosome 16 have been published in genome-wide analyses."

Of note, the team also found substantial heterogeneity in NOD2 itself, suggesting that the region is "more complex than previously thought."

Co-author Dallas Swallow, also from University College London, said: "This research will complement the work of those examining cellular and molecular changes, and ultimately lead to more personalised strategies for treatment. The next step is to search the rest of the genome.

"Importantly the work also shows that this method will allow more information to be derived from the valuable datasets collected by organisations such as the Wellcome Trust."

The results of this study are published in the American Journal of Human Genetics.

By Helen Albert

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