A Chromosome 8 Gene-Cluster Polymorphism with Low Human Beta-Defensin 2 Gene Copy Number Predisposes to Crohn Disease of the Colon  Klaus Fellermann,

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A Chromosome 8 Gene-Cluster Polymorphism with Low Human Beta-Defensin 2 Gene Copy Number Predisposes to Crohn Disease of the Colon  Klaus Fellermann, Daniel E. Stange, Elke Schaeffeler, Hartmut Schmalzl, Jan Wehkamp, Charles L. Bevins, Walter Reinisch, Alexander Teml, Matthias Schwab, Peter Lichter, Bernhard Radlwimmer, Eduard F. Stange  The American Journal of Human Genetics  Volume 79, Issue 3, Pages 439-448 (September 2006) DOI: 10.1086/505915 Copyright © 2006 The American Society of Human Genetics Terms and Conditions

Figure 1 A, Copy number ratios of ∼8,000 clones covering the whole genome, with a resolution of ∼0.5 Mb, are shown for patient X1604. The loci of the amylase and beta-defensin gene clusters are indicated. The red lines in panels A and B show the smoothed copy number ratio, as calculated by the GLAD algorithm. B, Copy number ratios of all clones on chromosome 8 of patient X1604. The beta-defensin locus on 8p23.1 is indicated. C, Detail of copy number ratios on 8p23.1 for patient X1604. The alpha-defensin and the two beta-defensin loci are shown by arrows, indicating the genomic orientation of the loci; “sequence gap” indicates a region where no human reference sequence is available. The genomic position, length, and name of genomic fragments covering the region of interest are displayed at the top. The red line indicates the average genomic position of the region that shows a CNP in our 20 hybridizations. D, Copy number ratios in the 8p23.1 region of 10 patients with colonic CD. E, Copy number ratios in the 8p23.1 region of 10 healthy control individuals. The American Journal of Human Genetics 2006 79, 439-448DOI: (10.1086/505915) Copyright © 2006 The American Society of Human Genetics Terms and Conditions

Figure 2 Distribution of HBD-2 gene copy numbers in the 169 controls from Stuttgart and Cleveland (A) and both surgical CD cohorts with ileal (B) and colonic resection (C) allocated to <4, 4, or >4 copies per genome. The difference in distribution between ileal and colonic resection was significant (P=.018 [χ2 test]). The American Journal of Human Genetics 2006 79, 439-448DOI: (10.1086/505915) Copyright © 2006 The American Society of Human Genetics Terms and Conditions

Figure 3 Distribution of HBD-2 gene copy numbers (<4, 4, or >4 copies per genome) in the European cohort as categorized into ileal disease (L1) (A), colonic disease (L2) (B), ileal and colonic disease (L3) (C), and UC (D). L2 (colonic CD) differed significantly from L1 (ileal CD) and controls (P=.037 and P=.002, respectively [χ2 test]). The American Journal of Human Genetics 2006 79, 439-448DOI: (10.1086/505915) Copyright © 2006 The American Society of Human Genetics Terms and Conditions

Figure 4 HBD-2 mRNA expression, with respect to HBD-2 gene copy number, in mucosal specimens from patients with CD and UC with rectal inflammation. The American Journal of Human Genetics 2006 79, 439-448DOI: (10.1086/505915) Copyright © 2006 The American Society of Human Genetics Terms and Conditions