Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes
Open Access
- 3 February 2011
- journal article
- Published by Springer Science and Business Media LLC in BMC Medicine
- Vol. 9 (1), 12
- https://doi.org/10.1186/1741-7015-9-12
Abstract
During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/This publication has 151 references indexed in Scilit:
- Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBDInflammatory Bowel Diseases, 2009
- Copy-number variations (CNVs) of the human sex steroid metabolizing genesUGT2B17andUGT2B28and their associations with aUGT2B15functional polymorphismHuman Mutation, 2009
- SRp38 Regulates Alternative Splicing and Is Required for Ca2+ Handling in the Embryonic HeartDevelopmental Cell, 2009
- Uracil in DNA: Consequences for carcinogenesis and chemotherapyBiochemical Pharmacology, 2008
- RetromerCurrent Opinion in Cell Biology, 2008
- Association Study of Wnt Signaling Pathway Genes in Bipolar DisorderArchives of General Psychiatry, 2008
- Neuronal Peroxisome Proliferator-Activated Receptor γ Signaling: Regulation by Mood-Stabilizer ValproateJournal of Molecular Neuroscience, 2008
- The Fine-Scale and Complex Architecture of Human Copy-Number VariationAmerican Journal of Human Genetics, 2008
- Global variation in copy number in the human genomeNature, 2006
- Regulating Gene Expression through RNA Nuclear RetentionCell, 2005