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High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12.

ABSTRACT: Epidemiological studies have shown that genetic factors contribute to the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Recent genome scans and replication studies have identified replicated linkage between CD and a locus on chromosome 16 (the IBD1 locus), replicated linkage between IBD (especially UC) and a locus on chromosome 12q (the IBD2 locus), and replicated linkage between IBD (especially CD) and a locus on chromosome 6p (the IBD3 locus). Since the estimated locus-specific lambdas values for the regions of replicated linkage do not account for the overall lambdas in CD, and since the published genome scans in IBD show at least nominal evidence for linkage to regions on all but two chromosomes, we performed an independent genome scan using 751 microsatellite loci in 127 CD-affected relative pairs from 62 families. Single-point nonparametric linkage analysis using the GENEHUNTER-PLUS program shows evidence for linkage to the adjacent D14S261 and D14S283 loci on chromosome 14q11-12 (LOD = 3.00 and 1.70, respectively), and the maximal multipoint LOD score is observed at D14S261 (LOD = 3.60). In the multipoint analysis, nominal evidence for linkage (P<.05) is observed near D2S117 (LOD = 1.25), near D3S3045 (LOD = 1.31), between D7S40 and D7S648 (LOD = 0.91), and near D18S61 (LOD = 1.15). Our finding of significant linkage to D14S261 and the finding of suggestive linkage to the same locus in an independent study (multipoint LOD = 2.8) satisfies criteria for confirmed linkage, so we propose that the region of interest on chromosome 14q11-12 should be designated the IBD4 locus.

SUBMITTER: Duerr RH

PROVIDER: S-EPMC1378032 | biostudies-other | 2000 Jun

REPOSITORIES: biostudies-other

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High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12.

Duerr R H RH Barmada M M MM Zhang L L Pfützer R R Weeks D E DE

American journal of human genetics 20000403 6

Epidemiological studies have shown that genetic factors contribute to the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Recent genome scans and replication studies have identified replicated linkage between CD and a locus on chromosome 16 (the IBD1 locus), replicated linkage between IBD (especially UC) and a locus on chromosome 12q (the IBD2 locus), and replicated linkage between IBD (especially CD) and a locus on chromosome 6p ...[more]

PMID: 10747815

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Project description:BACKGROUND: Linkage disequilibrium (LD) maps can provide a wealth of information on specific marker-phenotype relationships, especially in areas of the genome where positional candidate genes with similar functions are located. A recently published high resolution radiation hybrid map of bovine chromosome 14 (BTA14) together with the bovine physical map have enabled the creation of more accurate LD maps for BTA14 in both dairy and beef cattle. RESULTS: Over 500 Single Nucleotide Polymorphism (SNP) markers from both Angus and Holstein animals had their phased haplotypes estimated using GENOPROB and their pairwise r2 values compared. For both breeds, results showed that average LD extends at moderate levels up to 100 kilo base pairs (kbp) and falls to background levels after 500 kbp. Haplotype block structure analysis using HAPLOVIEW under the four gamete rule identified 122 haplotype blocks for both Angus and Holstein. In addition, SNP tagging analysis identified 410 SNPs and 420 SNPs in Holstein and Angus, respectively, for future whole genome association studies on BTA14. Correlation analysis for marker pairs common to these two breeds confirmed that there are no substantial correlations between r-values at distances over 10 kbp. Comparison of extended haplotype homozygosity (EHH), which calculates the LD decay away from a core haplotype, shows that in Holstein there is long range LD decay away from the DGAT1 region consistent with the selection for milk fat % in this population. Comparison of EHH values for Angus in the same region shows very little long range LD. CONCLUSION: Overall, the results presented here can be applied in future single or haplotype association analysis for both populations, aiding in confirming or excluding potential polymorphisms as causative mutations, especially around Quantitative Trait Loci regions. In addition, knowledge of specific LD information among markers will aid the research community in selecting appropriate markers for whole genome association studies.

Dataset Information

High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12.

Publications

High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12.

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