Jd. Rioux et al., Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci, AM J HU GEN, 66(6), 2000, pp. 1863-1870
Citations number
34
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcer
ative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointe
stinal tract. These conditions have a peak incidence in early adulthood and
a combined prevalence of similar to 100-200/100,000. Although the etiology
of IBD is multifactorial, a significant genetic contribution to disease su
sceptibility is implied by epidemiological data revealing a sibling risk of
similar to 35-fold for CD and similar to 15-fold for UC. To elucidate the
genetic basis for these disorders, we undertook a genomewide scan in 158 Ca
nadian sib-pair families and identified three regions of suggestive linkage
(Sp, 5q31-33, and Gp) and one region of significant linkage to 19p13 (LOD
score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus
of genomewide significance (LOD score 3.9) that contributes to CD susceptib
ility in families with early-onset disease. Both of these genomic regions c
ontain numerous genes that are important to the immune and inflammatory sys
tems and that provide good targets for future candidate-gene studies.