Mapping of a susceptibility locus for Crohn's disease on chromosome 16

CROHN'S disease (CD) and ulcerative colitis are the major forms of chronic inflammatory bowel diseases in the western world, and occur in young adults with an estimated prevalence of more than one per thousand inhabitants1. The causes of inflammatory bowel diseases remain unknown, but genetic epidemiology studies2–5 suggest that inherited factors may contribute in part to variation in individual susceptibility to Crohn's disease. A genome-wide search performed on two consecutive and independent panels of families with multiple affected members, using a non-parametric two-point sibling-pair linkage method, identified a putative CD-susceptibility locus on chromosome 16 (P < 0.01 for each panel). The localization was centred around loci D16S409 and D16S419 by using multipoint sibpair analysis (ref. 6, and J.M.O., manuscript submitted) (P < 1.5 x 10−5). This region of the genome contains candidate genes which may be relevant to the pathogenic mechanism of inflammatory bowel diseases.

[1]  P. Green Construction and comparison of chromosome 21 radiation hybrid and linkage maps using CRI-MAP. , 1992, Cytogenetics and cell genetics.

[2]  J. Ott Computer-simulation methods in human linkage analysis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Hugot,et al.  Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease. G.E.T.A.I.D. , 1994, American journal of medical genetics.

[4]  N. Risch Linkage strategies for genetically complex traits. II. The power of affected relative pairs. , 1990, American journal of human genetics.

[5]  J. Ott,et al.  Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. , 1985, American journal of human genetics.

[6]  T. Sørensen,et al.  Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis. , 1993, BMJ.

[7]  N Risch,et al.  Assessing the role of HLA-linked and unlinked determinants of disease. , 1987, American journal of human genetics.

[8]  Blackwelder Wc,et al.  A comparison of sib-pair linkage tests for disease susceptibility loci , 1985 .

[9]  T. Sørensen,et al.  Familial occurrence of inflammatory bowel disease. , 1991, The New England journal of medicine.

[10]  S. Hodge,et al.  The information contained in multiple sibling pairs , 1984, Genetic epidemiology.

[11]  U. Panzer,et al.  Impaired response of activated mononuclear phagocytes to interleukin 4 in inflammatory bowel disease. , 1995, Gastroenterology.

[12]  J. Todd,et al.  A genome-wide search for human type 1 diabetes susceptibility genes , 1994, Nature.

[13]  A. Sonnenberg,et al.  Epidemiology of inflammatory bowel disease among U.S. military veterans. , 1991, Gastroenterology.

[14]  H. White Maximum Likelihood Estimation of Misspecified Models , 1982 .

[15]  C. Lingwood,et al.  CD19 has a potential CD77 (globotriaosyl ceramide)-binding site with sequence similarity to verotoxin B-subunits: implications of molecular mimicry for B cell adhesion and enterohemorrhagic Escherichia coli pathogenesis , 1994, The Journal of experimental medicine.

[16]  E. Lander,et al.  Complete multipoint sib-pair analysis of qualitative and quantitative traits. , 1995, American journal of human genetics.

[17]  J. Witte,et al.  Genetic dissection of complex traits. , 1994, Nature genetics.

[18]  A. Mendeloff,et al.  Epidemiology of inflammatory bowel disease. , 1986, Epidemiologic reviews.

[19]  E. Lindberg,et al.  Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. , 1988, Gut.

[20]  D. Staunton,et al.  Targeted disruption of CD43 gene enhances T lymphocyte adhesion. , 1993, Journal of immunology.

[21]  J. Colombel,et al.  Incidence of inflammatory bowel disease in northern France (1988-1990). , 1994, Gut.

[22]  M. James,et al.  Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome llq , 1994, Nature.

[23]  H. Wiker,et al.  Antigen 85C on Mycobacterium bovis, BCG and M. tuberculosis promotes monocyte-CR3-mediated uptake of microbeads coated with mycobacterial products. , 1994, Immunology.

[24]  F. Majewski,et al.  The genetics of Crohn disease: complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives. , 1989, American journal of medical genetics.

[25]  Cécile Fizames,et al.  The 1993–94 Généthon human genetic linkage map , 1994, Nature Genetics.

[26]  N. Doggett,et al.  An integrated physical map of human chromosome 16. , 1995, Nature.