Alimentary TractEvidence for inflammatory bowel disease of a susceptibility locus on the X chromosome☆,☆☆
Section snippets
Patients
All patients were seen at the Gastroenterology Unit of the University Hospital Gasthuisberg Leuven. Diagnosis was established using conventional clinical, radiologic, endoscopic, and histologic criteria, as described previously.27 In the first stage, 56 families including 79 white sibling pairs (68 CD, 11 mixed) were studied (Table 2).
A family was called mixed if both CD and UC occurred within 1 family. Both parents were genotyped in 25 of 56 families (44.6%); in another 10 families (17.9%), 1
Stage 1
Twelve markers were analyzed in the first stage, covering 140 cM (96%) of the X chromosome. Results of the single-point analysis are shown in Table 3.Marker cM LOD (P value), overall LOD (P value), CD only DXS996 14 0.00 (0.50) 0.00 (0.50) DXS999 10 0.00 (0.50) 0.00 (0.50) DXS451 12 0.21 (0.16) 0.03 (0.36) DMD 1 0.17 (0.19) 0.13 (0.22) DXS538 4 1.52 (0.0041) 1.40 (0.006) DXS1068 10 1.00 (0.016) 1.14 (0.011) MAOB 12 0.13 (0.22) 0.10 (0.25) DXS991 16 0.32 (0.11) 0.90 (0.02) DXS990 10
Discussion
This is the most detailed molecular study on the contribution of the X chromosome in IBD yet reported. Previous studies have mainly concentrated on the autosomal regions where statistical methods are much more straightforward. Recent modifications of existing programs of NPL have allowed ourselves and other investigators10 to dissect the contribution of the X chromosome.
The present data provide suggestive evidence for the presence of an X-linked susceptibility locus in IBD. Exclusion mapping
References (43)
- et al.
Incidence and prevalence of ulcerative colitis and Crohn's disease in the county of Copenhagen, 1962–1978
Gastroenterology
(1982) - et al.
Familial occurrence and inheritance studies in inflammatory bowel disease
Neth J Med
(1996) - et al.
Familial aggregation in Crohn's disease: increased age adjusted risk and concordance in clinical characteristics
Gastroenterology
(1996) - et al.
Clinical characteristics of Crohn's disease in 72 families
Gastroenterology
(1996) - et al.
A genomewide analysis provides evidence for novel linkage in inflammatory bowel disease in a large European cohort
Am J Hum Genet
(1999) - et al.
High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12
Am J Hum Genet
(2000) - et al.
Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci
Am J Hum Genet
(2000) - et al.
Tumor necrosis factor microsatellites define a Crohn's disease associated haplotype on chromosome 6
Gastroenterology
(1996) - et al.
Linkage and association between inflammatory bowel disease and a locus on chromosome 12
Am J Hum Genet
(1998) - et al.
American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12
Gastroenterology
(1998)
Absence of linkage between inflammatory bowel disease and selected loci on chromosomes 3, 7, 12 and 16
Gastroenterology
Linkage analysis in the presence of errors IV: joint pseudomarker analysis of linkage and/or linkage disequilibrium on a mixture of pedigrees and singletons when the mode of inheritance cannot be accurately specified
Am J Hum Genet
True and false positive peaks in genomewide scans: applications of length biased sampling to linkage mapping
Am J Hum Genet
Familial aggregation of inflammatory bowel disease in northern Italy: a multicenter study
Gastroenterology
Inflammatory bowel disease in 67 families each with three of more affected first-degree relatives
Gastroenterology
The epidemiology of idiopathic inflammatory bowel disease
Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins
A study of heritability and the influence of smoking
Gut
Mapping of a susceptibility locus for Crohn's disease on chromosome 16
Nature
Two-stage genome wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12
Nat Genet
Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1
Proc Natl Acad Sci U S A
A genome wide search identifies potential new susceptibility loci for Crohn's disease
Inflamm Bowel Dis
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Inflammatory Bowel Disease
2013, Emery and Rimoin's Principles and Practice of Medical GeneticsMaternal imprinting and female predominance in familial Crohn's disease
2012, Journal of Crohn's and ColitisCitation Excerpt :Thus, we cannot exclude the possibility of the transmission through genetic variants located in mitochondrial DNA and mitochondrial DNA analysis has not been studied yet in this context in IBD populations. Concerning the transmission through variant(s) located on X-chromosome, a susceptibility locus on X-chromosome has been found in a linkage analysis study with basic population of familial IBD30,31 but the genome-wide meta-analysis did not find susceptibility loci on this chromosome.32 Although apparent absence of male transmission in familial CD fits ill with an important role for paragenetic factors in the risk of contracting familial IBD, there is still a slight bias towards female disease in our non-familial CD population.
Genetic variation in human disease and a new role for copy number variants
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Supported by the Funds for Scientific Research (FWO), Belgium (to S.V.), the Medical Research Council, U.K. (To M.P. and J.S.), and a grant from A. Lazzari.
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Address requests for reprints to: P. Rutgeerts, M.D., Ph.D., Gastroenterology Unit, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. e-mail: [email protected]; fax: (32) 16-344399.