In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 1 ( 2002-01-08), p. 321-326
Kurzfassung:
Heritable predisposition to inflammatory bowel disease (IBD) has
been demonstrated by epidemiological and genetic analysis. Linkage of IBD to broad regions of chromosome 16 has been
established by analysis of multiple populations. NOD2 ,
located on proximal 16q, was recently identified as an IBD gene. As the linkage regions on chromosome 16 are large, we have investigated the
possibility that NOD2 is not the only IBD gene located
on this chromosome. A high-density experiment using 39 microsatellite markers was performed to identify additional regions of
association, and to indicate areas of interest for further investigation. A triple-peaked configuration of the linkage curve with
peak logarithm of odds (lod) scores of 2.7, 3.2, and 3.1 was observed on proximal 16p, proximal 16q, and central 16q, respectively. The
cohort was stratified by coding individuals carrying the NOD2 single nucleotide polymorphism (SNP)8 and SNP13 “unknown.” Significance
at the central peak, corresponding to the genomic location of NOD2 , then decreased from 3.2 to 1.2. The maximal lod
scores on the proximal p-arm (lod = 2.1) and central q-arm (lod = 2.6) changed only moderately. An exploratory association
analysis (TRANSMIT) yielded a strong lead at D16S3068 ( P = 0.00028). The region around this marker was
further investigated by using anonymous SNPs. An associated haplotype containing three SNPs was identified (peak significance P = 0.00027, IBD phenotype). On stratification
based on NOD2 genotype, this significance increased to P = 0.0001. These results confirm the importance of NOD2 and provide evidence for a second IBD gene
located on chromosome 16p.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.261567999
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2002
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
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