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. 2004 Jul;53(7):980-6.
doi: 10.1136/gut.2003.034033.

Genome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis

S Vermeire  1 , P Rutgeerts, K Van Steen, S Joossens, G Claessens, M Pierik, M Peeters, R Vlietinck
Affiliations

Genome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis

S Vermeire et al. Gut. 2004 Jul.

"VSports最新版本" Abstract

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population VSports手机版. .

Methods: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software V体育安卓版. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. .

Results: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint non-parametric linkage (NPL) score 2. 57, p = 0. 004; and at D1S305-D1S252: NPL 2. 97, p = 0. 001), 4q (D4S406: NPL 1. 95, p = 0. 03), 6q16 (D6S314: NPL 2. 44, p = 0. 007), 10p12 (D10S197: NPL 2. 05, p = 0. 02), 11q22 (D11S35-D11S927: NPL 1. 95, p = 0. 02) 14q11-12 (D14S80: NPL 2. 41, p = 0. 008), 20p12 (D20S192: NPL 2. 7, p = 0. 003), and Xq (DXS990: NPL 1. 70, p = 0. 04). A total of 51. 4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. V体育ios版.

Conclusion: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population. VSports最新版本.

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Figures

Figure 1
Figure 1
The results of multipoint non-parametric analysis (Genehunter 1.2) for chromosomes 1–9 are plotted as the non-parametric linkage (NPL) score against the genetic distance in centimorgan (cM). Results for inflammatory bowel disease (IBD) overall, Crohn’s disease (CD) only, mixed families, and anti-Saccharomyces cerevisiae antibody positive (ASCA+) families are shown. The reported regions of linkage from previous scans are indicated.
Figure 2
Figure 2
The results of multipoint non-parametric analysis (Genehunter 1.2) for chromosomes 10–18 are plotted as the non-parametric linkage (NPL) score against the genetic distance in centimorgan (cM). Results for inflammatory bowel disease (IBD) overall, Crohn’s disease (CD) only, mixed families, and anti-Saccharomyces cerevisiae antibody positive (ASCA+) families are shown. The reported regions of linkage from previous scans are indicated.
Figure 3
Figure 3
The results of multipoint non-parametric analysis (Genehunter 1.2) for chromosomes 19–22 and chromosome X, and are plotted as the non-parametric linkage (NPL) score against the genetic distance in centimorgan (cM). Results for inflammatory bowel disease (IBD) overall, Crohn’s disease (CD) only, mixed families, and anti-Saccharomyces cerevisiae antibody positive (ASCA+) families are shown. The reported regions of linkage from previous scans are indicated.
Figure 4
Figure 4
Epistasis between loci: shown are the non-parametric multipoint linkage (NPL) curves of chromosomes 6 and 20 for the overall inflammatory bowel disease (IBD) group, and conditioned on the presence (+) or absence (−) of linkage to the observed susceptibility region on chromosome 10. Results are plotted as NPL score against the genetic distance in centimorgan (cM).
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