Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data.
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 collec...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0047597&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849727504509566976 |
|---|---|
| author | Allison R Baker Feiyou Qiu April Kaur Randhawa David J Horne Mark D Adams Muki Shey Jill Barnholtz-Sloan Harriet Mayanja-Kizza Gilla Kaplan Willem A Hanekom W Henry Boom Thomas R Hawn Catherine M Stein Tuberculosis Research Unit and South African Tuberculosis Vaccine Initiative Team |
| author_facet | Allison R Baker Feiyou Qiu April Kaur Randhawa David J Horne Mark D Adams Muki Shey Jill Barnholtz-Sloan Harriet Mayanja-Kizza Gilla Kaplan Willem A Hanekom W Henry Boom Thomas R Hawn Catherine M Stein Tuberculosis Research Unit and South African Tuberculosis Vaccine Initiative Team |
| author_sort | Allison R Baker |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1234d6fa91e74d0c86ff9b89e355e15b |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1234d6fa91e74d0c86ff9b89e355e15b2025-08-20T03:09:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4759710.1371/journal.pone.0047597Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data.Allison R BakerFeiyou QiuApril Kaur RandhawaDavid J HorneMark D AdamsMuki SheyJill Barnholtz-SloanHarriet Mayanja-KizzaGilla KaplanWillem A HanekomW Henry BoomThomas R HawnCatherine M SteinTuberculosis Research Unit and South African Tuberculosis Vaccine Initiative TeamGenetic 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0047597&type=printable |
| spellingShingle | Allison R Baker Feiyou Qiu April Kaur Randhawa David J Horne Mark D Adams Muki Shey Jill Barnholtz-Sloan Harriet Mayanja-Kizza Gilla Kaplan Willem A Hanekom W Henry Boom Thomas R Hawn Catherine M Stein Tuberculosis Research Unit and South African Tuberculosis Vaccine Initiative Team Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. PLoS ONE |
| title | Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. |
| title_full | Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. |
| title_fullStr | Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. |
| title_full_unstemmed | Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. |
| title_short | Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data. |
| title_sort | genetic variation in tlr genes in ugandan and south african populations and comparison with hapmap data |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0047597&type=printable |
| work_keys_str_mv | AT allisonrbaker geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT feiyouqiu geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT aprilkaurrandhawa geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT davidjhorne geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT markdadams geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT mukishey geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT jillbarnholtzsloan geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT harrietmayanjakizza geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT gillakaplan geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT willemahanekom geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT whenryboom geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT thomasrhawn geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT catherinemstein geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata AT tuberculosisresearchunitandsouthafricantuberculosisvaccineinitiativeteam geneticvariationintlrgenesinugandanandsouthafricanpopulationsandcomparisonwithhapmapdata |