9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.

      Nature genetics

      Chromosome Mapping, Chromosomes, Human, Pair 12, genetics, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 7, Colitis, Ulcerative, Crohn Disease, Genetic Predisposition to Disease, Genetic Testing, Genome, Human, Genotype, Humans, Lod Score, Microsatellite Repeats, Nuclear Family

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.

          Related collections

          Most cited references 23

          • Record: found
          • Abstract: found
          • Article: not found

          A comprehensive genetic map of the human genome based on 5,264 microsatellites.

          The great increase in successful linkage studies in a number of higher eukaryotes during recent years has essentially resulted from major improvements in reference genetic linkage maps, which at present consist of short tandem repeat polymorphisms of simple sequences or microsatellites. We report here the last version of the Généthon human linkage map. This map consists of 5,264 short tandem (AC/TG)n repeat polymorphisms with a mean heterozygosity of 70%. The map spans a sex-averaged genetic distance of 3,699 cM and comprises 2,335 positions, of which 2,032 could be ordered with an odds ratio of at least 1,000:1 against alternative orders. The average interval size is 1.6 cM; 59% of the map is covered by intervals of 2 cM at most and 1% remains in intervals above 10 cM.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Genetic dissection of complex traits

             E Lander,  N Schork (1994)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A genome-wide search for human type 1 diabetes susceptibility genes.

              We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis. In addition to IDDM1 (in the major histocompatibility complex on chromosome 6p21) and IDDM2 (in the insulin gene region on chromosome 11p15), eighteen different chromosome regions showed some positive evidence of linkage to disease. Linkages to chromosomes 11q (IDDM4) and 6q (IDDM5) were confirmed by replication, and chromosome 18 may encode a fifth disease locus. There are probably no genes with large effects aside from IDDM1. Therefore polygenic inheritance is indicated, with a major locus at the major histocompatibility complex.
                Bookmark

                Author and article information

                Journal
                8841195
                10.1038/ng1096-199

                Comments

                Comment on this article