American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12

Brant, Steven R.; Fu, Yifan; Fields, Carter T.; Baltazar, Romulo; Ravenhill, Geoffrey; Pickles, Michael; Rohal, Patrick M.; Mann, Jasdeep; Kirschner, Barbara S.; Jabs, Ethylin Wang; Bayless, Theodore M.; Hanauer, Stephen B.; Cho, Judy H.

doi:10.1016/s0016-5085(98)70073-3

Cited by 131 publications

(52 citation statements)

References 17 publications

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“…This region of the human genome harbors one or more genes implicated in modifying the risk for the development of inflammatory bowel disease (42,43). This coincidence led us to examine a possible role for mouse IRE1β in the development of experimental inflammatory bowel disease.…”

Section: Resultsmentioning

confidence: 99%

Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice

Bertolotti¹,

Wang²,

Novoa³

et al. 2001

J. Clin. Invest.

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372

352

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The epithelial cells of the gastrointestinal tract are exposed to toxins and infectious agents that can adversely affect protein folding in the endoplasmic reticulum (ER) and cause ER stress. The IRE1 genes are implicated in sensing and responding to ER stress signals. We found that epithelial cells of the gastrointestinal tract express IRE1β, a specific isoform of IRE1. BiP protein, a marker of ER stress, was elevated in the colonic mucosa of IRE1β -/-mice, and, when exposed to dextran sodium sulfate (DSS) to induce inflammatory bowel disease, mutant mice developed colitis 3-5 days earlier than did wild-type or IRE1β +/-mice. The inflammation marker ICAM-1 was also expressed earlier in the colonic mucosa of DSS-treated IRE1β -/-mice, indicating that the mutation had its impact early in the inflammatory process, before the onset of mucosal ulceration. These findings are consistent with a model whereby perturbations in ER function, which are normally mitigated by the activity of IRE1β, participate in the development of colitis.

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Section: Resultsmentioning

confidence: 99%

Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice

Bertolotti¹,

Wang²,

Novoa³

et al. 2001

J. Clin. Invest.

Self Cite

372

352

View full text Add to dashboard Cite

show abstract

“…23,24,52,53 These studies also failed to see linkage. To date, six genome scans and four replication studies have failed to detect linkage to chromosome 7.…”

Section: Confirmation Of Linkage To Ibd3mentioning

confidence: 97%

Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3)

et al. 2001

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Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine, commonly diagnosed as either ulcerative colitis (UC) or Crohn's disease (CD). Epidemiological studies have consistently shown that both genetic and environmental factors influence the pathogenesis of IBD. A number of genome scans have been conducted in cohorts of IBD families with affected sibling pairs (ASPs) to identify chromosomal regions that harbour IBD susceptibility genes. Several putative linked loci have been identified, including two loci on chromosomes 16 and 12, IBD1 and IBD2, which have subsequently been replicated by independent regionspecific studies. We have conducted both a replication study on another linkage region, chromosome 6p (IBD3), and extension studies on two other regions, chromosomes 3p and 7q. Microsatellite markers across each region were genotyped in 284 IBD ASPs from 234 families. A nonparametric peak multipoint LOD score of 3.0 was observed near D6S291, replicating the previous linkage to chromosome 6p (IBD3). Nominal evidence of linkage was observed at both the 3p and 7q regions.

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“…Whilst most of them have confirmed the data for chromosomes 16 and 12, none has so far been able to confirm linkage for chromosomes 3 and 7. [8][9][10][11][12][13][14][15][16] In this study we tested the presence of potential susceptibility loci on chromosomes 3, 6, 7, 12 and 16 in a series of Italian families with IBD.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus – A GISC study

et al. 1999

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Epidemiological studies suggest that inherited factors influence susceptibility to inflammatory bowel disease (IBD), and some candidate loci have been described. In order to verify whether the same loci are responsible for predisposition to IBD in our population, we carried out a linkage study in a series of 58 Italian families with Crohn's disease (CD) and ulcerative colitis (UC). HLA-DQ alleles, motilin gene, and 34 microsatellites flanking the previously described loci on chromosomes 3, 6, 7, 12 and 16 were analysed by non-parametric linkage analysis in 16 and 23 families with CD and UC, respectively, and in 19 families where CD and UC coexisted. Non parametric analysis using GENEHUNTER yielded maximum NPL scores for marker D16S408 in all IBD families combined (2.71, P = 0.003), for marker D16S419 in CD (1.97, P = 0.026) and for marker D16S514 in UC families (2.44, P = 0.007). These markers map in the previously described IBD1 region. No significant linkage was found for markers of chromosomes 3, 6, 7 and 12. The present study performed in a Southern European population provides additional support for the conclusion that the IBD1 locus has a clear role in the genetic susceptibility to IBD.

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American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12

Cited by 131 publications

References 17 publications

Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice

Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice

Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3)

Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus – A GISC study

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