Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes

dc.contributor.authorPrescott, Natalie Jen_ZA
dc.contributor.authorLehne, Benjaminen_ZA
dc.contributor.authorStone, Kristinaen_ZA
dc.contributor.authorLee, James Cen_ZA
dc.contributor.authorTaylor, Kirstinen_ZA
dc.contributor.authorKnight, Joen_ZA
dc.contributor.authorPapouli, Efterpien_ZA
dc.contributor.authorMirza, Muddassar Men_ZA
dc.contributor.authorSimpson, Michael Aen_ZA
dc.contributor.authorSpain, Sarah Len_ZA
dc.date.accessioned2015-11-23T12:35:49Z
dc.date.available2015-11-23T12:35:49Z
dc.date.issued2015en_ZA
dc.description.abstractAuthor Summary Crohn's disease and ulcerative colitis are two forms of inflammatory bowel disease which cause chronic inflammation of the gastrointestinal tract. Common genetic variants in more than 160 regions of the human genome have been associated with an altered risk of these disorders, but leave much of the estimated genetic contribution to disease risk unexplained. We sought to establish whether rare genetic variants which alter the structure or function of the proteins encoded by genes also contribute to disease susceptibility. We used high throughput DNA sequencing to screen over 500 genes for such variants in nearly 500 patients and controls, and validated interesting variants in about 10,000 patients and 7,000 controls. We detected association of a limited number of rare variants from coding regions with disease, suggesting that they do not account for a large proportion of genetic susceptibility. However, they highlight the involvement of genes of potential importance in the development of inflammatory bowel disease, including those involved in the activation of immune cells, the regulation of immune response genes, and the degradation of proteins in cells.en_ZA
dc.identifier.apacitationPrescott, N. J., Lehne, B., Stone, K., Lee, J. C., Taylor, K., Knight, J., ... Spain, S. L. (2015). Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes. <i>PLOS Genetics</i>, http://hdl.handle.net/11427/15331en_ZA
dc.identifier.chicagocitationPrescott, Natalie J, Benjamin Lehne, Kristina Stone, James C Lee, Kirstin Taylor, Jo Knight, Efterpi Papouli, Muddassar M Mirza, Michael A Simpson, and Sarah L Spain "Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes." <i>PLOS Genetics</i> (2015) http://hdl.handle.net/11427/15331en_ZA
dc.identifier.citationPrescott, N. J., Lehne, B., Stone, K., Lee, J. C., Taylor, K., Knight, J., ... & UK IBD Genetics Consortium. (2015). Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes. PLoS Genet, 11(2), e1004955. doi:10.1371/journal.pgen.1004955en_ZA
dc.identifier.ris TY - Journal Article AU - Prescott, Natalie J AU - Lehne, Benjamin AU - Stone, Kristina AU - Lee, James C AU - Taylor, Kirstin AU - Knight, Jo AU - Papouli, Efterpi AU - Mirza, Muddassar M AU - Simpson, Michael A AU - Spain, Sarah L AB - Author Summary Crohn's disease and ulcerative colitis are two forms of inflammatory bowel disease which cause chronic inflammation of the gastrointestinal tract. Common genetic variants in more than 160 regions of the human genome have been associated with an altered risk of these disorders, but leave much of the estimated genetic contribution to disease risk unexplained. We sought to establish whether rare genetic variants which alter the structure or function of the proteins encoded by genes also contribute to disease susceptibility. We used high throughput DNA sequencing to screen over 500 genes for such variants in nearly 500 patients and controls, and validated interesting variants in about 10,000 patients and 7,000 controls. We detected association of a limited number of rare variants from coding regions with disease, suggesting that they do not account for a large proportion of genetic susceptibility. However, they highlight the involvement of genes of potential importance in the development of inflammatory bowel disease, including those involved in the activation of immune cells, the regulation of immune response genes, and the degradation of proteins in cells. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pgen.1004955 DP - University of Cape Town J1 - PLOS Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes TI - Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes UR - http://hdl.handle.net/11427/15331 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15331
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pgen.1004955
dc.identifier.vancouvercitationPrescott NJ, Lehne B, Stone K, Lee JC, Taylor K, Knight J, et al. Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes. PLOS Genetics. 2015; http://hdl.handle.net/11427/15331.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2015 Prescott et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Geneticsen_ZA
dc.source.urihttp://journals.plos.org/plosgeneticsen_ZA
dc.subject.otherGene poolen_ZA
dc.subject.otherInflammatory bowel diseaseen_ZA
dc.subject.otherGenome-wide association studiesen_ZA
dc.subject.otherGenotypingen_ZA
dc.subject.otherAllelesen_ZA
dc.subject.otherGene sequencingen_ZA
dc.subject.otherVariant genotypesen_ZA
dc.subject.otherCrohn's diseaseen_ZA
dc.titlePooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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