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The genetics of Crohn’s disease decoded
1/18/13

Studying 75,000 patients

This study is an extraordinary scientific adventure. Several years ago, a number of laboratories specialising in the genetics of Crohn’s disease attempted to be the first to discover one or more genes associated with the disease. A team from the University of Liège’s Giga Research (led by professors Michel Georges and Edouard Louis) was in the race. Thanks to collaborations between several of the country’s major hospitals, the team in Liège managed to recruit some 3,000 people for their study (1700 sufferers and 1500 non-sufferers as the control group). A statistically sufficient amount to isolate an initial gene that is clearly involved in Crohn’s disease. In fact, our researchers revealed several variants in the same genetic sequence, one of which is present in 20 % of people with Crohn’s and in only 12 % of healthy patients (read the article).

But we realised that in order to go further, we would have to work on a larger number of patients”, Professor Edouard Louis explains. “Four teams were working on this research: NIH in the USA, the Wellcome Trust Centre in the UK, Kiel University in Germany and GIGA in Liège. Despite the scientific competition, this happened very spontaneously, since it was in everyone’s interest to work together. Three telephone calls and it was sorted.” Three telephone calls to create a global science consortium (today, some 30 countries are involved) responsible for recruiting patients from the four corners of the world, performing a genetic analysis on intestinal tissue samples and recently published a very complete set of results in Nature magazine, relating to 75,000 patients this time. Just as spectacular in this study is the number of genetic variants revealed that are associated with Crohn’s disease: 163, 71 of which were absolutely unknown! “We have doubled the knowledge we have on the disease. No other pathology is currently better genotyped than Crohn's", says a delighted Edouard Louis.

(EN)-puce-et-scannerThis important breakthrough was made possible by the vast meta-analysis (cross-checking and comparison) of 15 previous studies, including those carried out in Liège in 2008. But also thanks to the use of specific genetic equipment: a genetic chip (Immunochip) specially developed for the study of immune diseases: Crohn’s, diabetes, psoriasis, rheumatoid arthritis, etc. The miniaturisation achieved in this type of equipment exceeds all expectations. A chip measures 12 cm2 and can analyse the DNA of 12 patients, i.e. 1 cm2 per patient. Millions of tiny beads, each containing single DNA strands, are attached to every square centimetre of the chip. The study tested 196,000 different ones, each of which contained a genetic variant (Single Nucleotide Polymorphism or SNP) likely to be involved in Crohn's disease. Once placed on the chip, the patient’s DNA sample will recombine with the strands attached to the chip if the genetic sequence is the same, in other words, if the patient carries one of the 196,000 variants tested on the chip.

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