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

Slides:

Advertisements

Similar presentations

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.

Advertisements

Gene Preference in Maple Syrup Urine Disease Mary M. Nellis, Dean J. Danner The American Journal of Human Genetics Volume 68, Issue 1, Pages (January.

Association of a Nkx2-3 polymorphism with Crohn's disease and expression of Nkx2-3 is up-regulated in B cell lines and intestinal tissues with Crohn's.

Public awareness of Crohn's disease and ulcerative colitis: A national survey Sieglinde Angelberger, Harald Vogelsang, Gottfried Novacek, Wolfgang Miehsler,

Volume 128, Issue 2, Pages (February 2005)

Kendy K. Wong, Ronald J. deLeeuw, Nirpjit S. Dosanjh, Lindsey R

Transmission/Disequilibrium Tests for Extended Marker Haplotypes

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome Michel De Vos, Bruce E. Hayward, Susan Picton,

Volume 136, Issue 2, Pages (February 2009)

Jacek Majewski The American Journal of Human Genetics

Rapid Simulation of P Values for Product Methods and Multiple-Testing Adjustment in Association Studies S.R. Seaman, B. Müller-Myhsok The American Journal.

Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease Yi-An Ko, Huiguang Yi, Chengxiang Qiu, Shizheng.

Der(22) Syndrome and Velo-Cardio-Facial Syndrome/DiGeorge Syndrome Share a 1.5- Mb Region of Overlap on Chromosome 22q11 B. Funke, L. Edelmann, N. McCain,

Diagnostic Genome Profiling in Mental Retardation

Molecular Diagnosis of Autosomal Dominant Polycystic Kidney Disease Using Next- Generation Sequencing Adrian Y. Tan, Alber Michaeel, Genyan Liu, Olivier.

Alterations of the Cell-Cycle Inhibitors p27KIP1 and p16INK4a Are Frequent in Blastic Plasmacytoid Dendritic Cell Neoplasms Thomas Wiesner, Anna C. Obenauf,

Volume 128, Issue 2, Pages (February 2005)

Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors Michael Dannemann, Aida M.

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

High-Resolution Mapping of Genotype-Phenotype Relationships in Cri du Chat Syndrome Using Array Comparative Genomic Hybridization Xiaoxiao Zhang, Antoine.

Pathogenic Escherichia coli in inflammatory bowel diseases

Comparing Algorithms for Genotype Imputation

Gene Copy-Number Variation and Associated Polymorphisms of Complement Component C4 in Human Systemic Lupus Erythematosus (SLE): Low Copy Number Is a.

Genetic Variation in the Human Androgen Receptor Gene Is the Major Determinant of Common Early-Onset Androgenetic Alopecia Axel M. Hillmer, Sandra Hanneken,

Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD

Association of a Nkx2-3 polymorphism with Crohn's disease and expression of Nkx2-3 is up-regulated in B cell lines and intestinal tissues with Crohn's.

Molecular Cytogenetic Evidence for a Common Breakpoint in the Largest Inverted Duplications of Chromosome 15 A.E. Wandstrat, J. Leana-Cox, L. Jenkins,

Caroline Durrant, Krina T. Zondervan, Lon R

Microsatellite Polymorphism in the Heme Oxygenase-1 Gene Promoter Is Associated with Susceptibility to Emphysema Norihiro Yamada, Mutsuo Yamaya, Shoji.

Catherine E. Keegan, Anthony A. Killeen

Elizabeth Theusch, Analabha Basu, Jane Gitschier

Weight Loss after Gastric Bypass Is Associated with a Variant at 15q26

Gene-Expression Variation Within and Among Human Populations

Highly Significant Linkage to the SLI1 Locus in an Expanded Sample of Individuals Affected by Specific Language Impairment The American Journal of.

Discovery of three related females who type XY at the amelogenin locus

Hemizygosity at the NCF1 Gene in Patients with Williams-Beuren Syndrome Decreases Their Risk of Hypertension Miguel Del Campo, Anna Antonell, Luis F.

Volume 124, Issue 1, Pages (January 2003)

Kristina Allen-Brady, Peggy A. Norton, James M

Towfique Raj, Manik Kuchroo, Joseph M

Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males Hilde Van Esch, Marijke.

John D. Rioux, Valerie A. Stone, Mark J

Sherlock: Detecting Gene-Disease Associations by Matching Patterns of Expression QTL and GWAS Xin He, Chris K. Fuller, Yi Song, Qingying Meng, Bin Zhang,

Loci Related to Metabolic-Syndrome Pathways Including LEPR,HNF1A, IL6R, and GCKR Associate with Plasma C-Reactive Protein: The Women's Genome Health Study

Catarina D. Campbell, Nick Sampas, Anya Tsalenko, Peter H

Human Genomic Deletions Mediated by Recombination between Alu Elements

Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation Janine Wagenstaller, Stephanie.

High-Resolution Molecular Characterization of 15q11-q13 Rearrangements by Array Comparative Genomic Hybridization (Array CGH) with Detection of Gene Dosage

David C. Page The American Journal of Human Genetics

Hal M. Hoffman, Fred A. Wright, David H. Broide, Alan A

Highly Punctuated Patterns of Population Structure on the X Chromosome and Implications for African Evolutionary History Charla A. Lambert, Caitlin F.

Erratum The American Journal of Human Genetics

E.J. Hollox, J.A.L. Armour, J.C.K. Barber

Benjamin A. Rybicki, Robert C. Elston

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome Michel De Vos, Bruce E. Hayward, Susan Picton,

Identifying Novel Genes for Atherosclerosis through Mouse-Human Comparative Genetics Xiaosong Wang, Naoki Ishimori, Ron Korstanje, Jarod Rollins, Beverly.

L-GATOR: Genetic Association Testing for a Longitudinally Measured Quantitative Trait in Samples with Related Individuals Xiaowei Wu, Mary Sara McPeek

Xiang Wan, Can Yang, Qiang Yang, Hong Xue, Xiaodan Fan, Nelson L. S

Constitutional Mutations of the hSNF5/INI1 Gene Predispose to a Variety of Cancers Nicolas Sévenet, Eammon Sheridan, Daniel Amram, Pascale Schneider,

Madhumathi Rao, MD, V.S. Balakrishnan, MD, PhD

Der(22) Syndrome and Velo-Cardio-Facial Syndrome/DiGeorge Syndrome Share a 1.5- Mb Region of Overlap on Chromosome 22q11 B. Funke, L. Edelmann, N. McCain,

Mapping of the Major Psoriasis-Susceptibility Locus (PSORS1) in a 70-Kb Interval around the Corneodesmosin Gene (CDSN) Sandro Orrù, Erika Giuressi, Carlo.

Test for Interaction between Two Unlinked Loci

Psoriasis Genetics: The Way Forward

Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci Eilis Hannon, Mike Weedon, Nicholas Bray,

Whole-chromosome view of gene density, inverse environmental variation, inverse total variation, and open chromatin signature. Whole-chromosome view of.

Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors Michael Dannemann, Aida M.

Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males Hilde Van Esch, Marijke.

Genomewide Comparison of DNA Sequences between Humans and Chimpanzees

E. Ekelund, A. Sääf, M. Tengvall-Linder, E. Melen, J. Link, J

Bruce Rannala, Jeff P. Reeve The American Journal of Human Genetics

Presentation transcript:

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