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

Hugot, Jean‐Pierre; Laurent‐Puig, Pierre; Gower‐Rousseau, Corinne; Olson, Jane M.; Lee, John C.; Beaugerie, Laurent; Naom, Isam; Dupas, Jean‐Louis; Gossum, A. Van; Af, Groupe d'Etude Thérapeutique des; Orholm, Marianne; Bonaïti‐Pellié, Catherine; Weissenbach, Jean; Mathew, Christopher; Lennard‐Jones, J. E.; Cortot, Antoine; Colombel, Jean–Frédéric; Thomas, Gilles

doi:10.1038/379821a0

Cited by 865 publications

(510 citation statements)

References 20 publications

Supporting

Mentioning

463

Contrasting

Unclassified

Order By: Relevance

“…35,36 IBD5, a Crohn's disease (CD) susceptibility locus on 5q31-33, is 13 cM centromeric to D5S211, 37 but D5S211 is too distant to provide much support that this Crohn's locus is involved in sarcoidosis susceptibility. A major susceptibility locus for CD is located on chromosome 16 (IBD1) 38 and mutations in the leucine-rich region (LRR) of the CARD15 (NOD2) (MIM 605956) gene associated with CD have been discovered. [39][40][41] We previously found no evidence of linkage of this locus to sarcoidosis, 42 and Schurmann et al 35 also could not find evidence that CARD15 mutations are associated with sarcoidosis.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide search for sarcoidosis susceptibility genes in African Americans

et al. 2005

View full text Add to dashboard Cite

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P ¼ 0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide search for sarcoidosis susceptibility genes in African Americans

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Linkage analyses demonstrated evidence of the linkage of both CD and UC to regions flanked by microsatellite markers on chromosomes 3, 7, and 12 (lod score 5.47) [3]. Other studies support the linkage of CD to a region on chromosome 16, with no contribution to UC susceptibility [4,5]. A recent study using nonparametric analyses of microsatellites in the region of the tumor necrosis factor (TNF) on chromosome 6 supported the linkage of CD with the major histocompatibility complex (MHC) region [6].…”

Section: Introductionmentioning

confidence: 94%

“…Recent genetic studies to identify specific IBD susceptibility genes have focused on genome-wide scans with anonymous DNA markers, providing some evidence of susceptibility loci on chromosomes 3, 7, and 12 [3], and chromosome 16 [4,5]. Linkage analyses demonstrated evidence of the linkage of both CD and UC to regions flanked by microsatellite markers on chromosomes 3, 7, and 12 (lod score 5.47) [3].…”

Section: Introductionmentioning

confidence: 99%

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Trachtenberg¹,

Yang

Hayes³

et al. 2000

Human Immunology

View full text Add to dashboard Cite

Ulcerative colitis (UC) and Crohn's disease (CD) are the clinical entities comprising idiopathic inflammatory bowel disease (IBD). Previous studies on the association of IBD and human leukocyte antigen (HLA) class II genes suggested a role for HLA in this disease. Here we present HLA class II (DRB1, DQB1, DQA1, DPB1) allele and haplotype distributions determined using the polymerase chain reaction and sequence-specific oligonucleotide probe methods. A total of 578 UC and CD Caucasian patients and controls from Jewish (Ashkenazi) and non-Jewish populations was examined. Our previously reported association of DR1-DQ5 with CD was attributable to DRB1*0103. A dramatic association with IBD and the highly unusual DRB1*0103-DQA1*0501-DQB1*0301 haplotype (OR = 6.6, p = 0.036) was found. The more common DR1 haplotype, DRB1*0103-DQA1*0101-DQB1*0501, was also associated with IBD (OR = 3.1, p = 0.014), a result suggesting that interaction between DR and DQ may determine the extent of disease risk. Our previously reported association of DR2 with UC was attributable to DRB1*1502 (OR = 2.6, p = 0.006). At the DPB1 locus, a significant association of DPB1*0401 with CD was observed for the combined populations (OR = 1.85, p = 0.007). These observations indicate that some class II alleles and haplotypes confer susceptibility to both UC and CD, implying common immunogenetic mechanisms of pathogenesis, while others confer risk to only one of these diseases, and illustrate the value of DNA HLA typing in disease susceptibility analyses.

show abstract

“…Of the several putative susceptibility loci for CD, the Crohn's IBD1 locus on 16q between markers D16S409 and D16S419 (56.1-65.6 cM from p-telomere) (12)(13)(14) overlaps with that of Blau syndrome. In the present study, we further refined the Blau susceptibility interval by genotyping additional families.…”

mentioning

confidence: 99%

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

Wang¹,

Kuivaniemi²,

Bonavita³

et al. 2002

Arthritis & Rheumatism

124

View full text Add to dashboard Cite

Objective. To analyze the CARD15 gene in families with heritable multi-organ granulomatoses, including the original Blau syndrome kindred as well as other families with related granulomatous conditions.Methods. Linkage mapping was performed in 10 families. Observed recombination events were used to exclude regions centromeric or telomeric to 16q12.1, and the Blau gene critical region was refined to <3 cM, corresponding to a physical distance of 3.5 megabasepairs. Based on its known biochemical function, CARD15 was analyzed as a positional candidate for the Blau syndrome susceptibility gene, by direct DNA sequencing.Results. These studies resulted in the identification, in 5 of the families, of 2 sequence variants at position 334 of the gene product (R334W and R334Q). Affected family members from the original Blau syndrome kindred were heterozygous for the R334W missense mutation; mutations at the same position were also observed in several unrelated Blau syndrome families, some of whose phenotypes included large-vessel arteritis and cranial neuropathy. The missense mutations segregated with the disease phenotype in the families, and were not seen in 208 control alleles.Conclusion. These findings demonstrate that CARD15 is an important susceptibility gene for Blau syndrome and for other familial granulomatoses that display phenotypic traits beyond those of classic Blau syndrome.

show abstract

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

Cited by 865 publications

References 20 publications

Genome-wide search for sarcoidosis susceptibility genes in African Americans

Genome-wide search for sarcoidosis susceptibility genes in African Americans

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large‐vessel arteritis and cranial neuropathy

Contact Info

Product

Resources

About