Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes
| Autor: | A E Wiskin, Claire Willis, Nadeem A. Afzal, Andrew Collins, Katja Christodoulou, Sarah Ennis, Jane Gibson, R Mark Beattie, Michael A. Simpson, John W. Holloway, William J. Tapper, Rosanna Upstill-Goddard |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Candidate gene Adolescent crohn's disease DNA Mutational Analysis Nod2 Signaling Adaptor Protein Human leukocyte antigen Biology Bioinformatics paediatric gastroenterology Frameshift mutation Cohort Studies 03 medical and health sciences 0302 clinical medicine Crohn Disease Gene Frequency Genetic predisposition Humans Computer Simulation Exome Genetic Predisposition to Disease Age of Onset Child Allele frequency Genetic Association Studies Exome sequencing ulcerative colitis 030304 developmental biology Genetic association Genetics 0303 health sciences zollinger ellison syndrome Models Genetic Inflammatory Bowel Disease IBD-genetics Gastroenterology Inflammatory Bowel Diseases 3. Good health Phenotype Child Preschool Mutation Colitis Ulcerative Female 030211 gastroenterology & hepatology Common disease-common variant |
| Zdroj: | Gut |
| ISSN: | 1468-3288 0017-5749 |
| DOI: | 10.1136/gutjnl-2011-301833 |
| Popis: | Background Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. Objective To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. Design DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. Results Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of |
| Databáze: | OpenAIRE |
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