Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data

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dc.contributor.authorBaker, Allison Ren_ZA
dc.contributor.authorQiu, Feiyouen_ZA
dc.contributor.authorRandhawa, April Kauren_ZA
dc.contributor.authorHorne, David Jen_ZA
dc.contributor.authorAdams, Mark Den_ZA
dc.contributor.authorShey, Mukien_ZA
dc.contributor.authorBarnholtz-Sloan, Jillen_ZA
dc.contributor.authorMayanja-Kizza, Harrieten_ZA
dc.contributor.authorKaplan, Gillaen_ZA
dc.contributor.authorHanekom, Willem Aen_ZA
dc.contributor.authorBoom, W Henryen_ZA
dc.contributor.authorHawn, Thomas Ren_ZA
dc.contributor.authorStein, Catherine Men_ZA
dc.date.accessioned2016-01-11T06:52:14Z
dc.date.available2016-01-11T06:52:14Z
dc.date.issued2012en_ZA
dc.description.abstractGenetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts.en_ZA
dc.identifier.apacitationBaker, A. R., Qiu, F., Randhawa, A. K., Horne, D. J., Adams, M. D., Shey, M., ... Stein, C. M. (2012). Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. <i>PLoS One</i>, http://hdl.handle.net/11427/16260en_ZA
dc.identifier.chicagocitationBaker, Allison R, Feiyou Qiu, April Kaur Randhawa, David J Horne, Mark D Adams, Muki Shey, Jill Barnholtz-Sloan, et al "Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16260en_ZA
dc.identifier.citationBaker, A. R., Qiu, F., Randhawa, A. K., Horne, D. J., Adams, M. D., Shey, M., ... & Boom, W. H. (2011). Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. PloS one, 7(10), e47597. doi:10.1371/journal.pone.0047597en_ZA
dc.identifier.ris TY - Journal Article AU - Baker, Allison R AU - Qiu, Feiyou AU - Randhawa, April Kaur AU - Horne, David J AU - Adams, Mark D AU - Shey, Muki AU - Barnholtz-Sloan, Jill AU - Mayanja-Kizza, Harriet AU - Kaplan, Gilla AU - Hanekom, Willem A AU - Boom, W Henry AU - Hawn, Thomas R AU - Stein, Catherine M AB - Genetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0047597 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data TI - Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data UR - http://hdl.handle.net/11427/16260 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16260
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0047597
dc.identifier.vancouvercitationBaker AR, Qiu F, Randhawa AK, Horne DJ, Adams MD, Shey M, et al. Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. PLoS One. 2012; http://hdl.handle.net/11427/16260.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentSouth African Tuberculosis Vaccine Initiative (SATVI)en_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© 2012 Baker et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherHaplotypesen_ZA
dc.subject.otherPopulation geneticsen_ZA
dc.subject.otherToll-like receptorsen_ZA
dc.subject.otherAfricansen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherGenetic epidemiologyen_ZA
dc.subject.otherSequence databasesen_ZA
dc.subject.otherGenetics of diseaseen_ZA
dc.titleGenetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap dataen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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