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Haplotypic analysis of the TNF locus by association efficiency and entropy
BACKGROUND: To understand the causal basis of TNF associations with disease, it is necessary to understand the haplotypic structure of this locus. We genotyped 12 single-nucleotide polymorphisms (SNPs) distributed over 4.3 kilobases in 296 healthy, unrelated Gambian and Malawian adults. We generated...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154575/ https://www.ncbi.nlm.nih.gov/pubmed/12702205 http://dx.doi.org/10.1186/gb-2003-4-4-r24 |
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author | Ackerman, Hans Usen, Stanley Mott, Richard Richardson, Anna Sisay-Joof, Fatoumatta Katundu, Pauline Taylor, Terrie Ward, Ryk Molyneux, Malcolm Pinder, Margaret Kwiatkowski, Dominic P |
author_facet | Ackerman, Hans Usen, Stanley Mott, Richard Richardson, Anna Sisay-Joof, Fatoumatta Katundu, Pauline Taylor, Terrie Ward, Ryk Molyneux, Malcolm Pinder, Margaret Kwiatkowski, Dominic P |
author_sort | Ackerman, Hans |
collection | PubMed |
description | BACKGROUND: To understand the causal basis of TNF associations with disease, it is necessary to understand the haplotypic structure of this locus. We genotyped 12 single-nucleotide polymorphisms (SNPs) distributed over 4.3 kilobases in 296 healthy, unrelated Gambian and Malawian adults. We generated 592 high-quality haplotypes by integrating family- and population-based reconstruction methods. RESULTS: We found 32 different haplotypes, of which 13 were shared between the two populations. Both populations were haplotypically diverse (gene diversity = 0.80, Gambia; 0.85, Malawi) and significantly differentiated (p < 10(-5 )by exact test). More than a quarter of marker pairs showed evidence of intragenic recombination (29% Gambia; 27% Malawi). We applied two new methods of analyzing haplotypic data: association efficiency analysis (AEA), which describes the ability of each SNP to detect every other SNP in a case-control scenario; and the entropy maximization method (EMM), which selects the subset of SNPs that most effectively dissects the underlying haplotypic structure. AEA revealed that many SNPs in TNF are poor markers of each other. The EMM showed that 8 of 12 SNPs (Gambia) and 7 of 12 SNPs (Malawi) are required to describe 95% of the haplotypic diversity. CONCLUSIONS: The TNF locus in the Gambian and Malawi sample is haplotypically diverse and has a rich history of intragenic recombination. As a consequence, a large proportion of TNF SNPs must be typed to detect a disease-modifying SNP at this locus. The most informative subset of SNPs to genotype differs between the two populations. |
format | Text |
id | pubmed-154575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-1545752003-05-08 Haplotypic analysis of the TNF locus by association efficiency and entropy Ackerman, Hans Usen, Stanley Mott, Richard Richardson, Anna Sisay-Joof, Fatoumatta Katundu, Pauline Taylor, Terrie Ward, Ryk Molyneux, Malcolm Pinder, Margaret Kwiatkowski, Dominic P Genome Biol Research BACKGROUND: To understand the causal basis of TNF associations with disease, it is necessary to understand the haplotypic structure of this locus. We genotyped 12 single-nucleotide polymorphisms (SNPs) distributed over 4.3 kilobases in 296 healthy, unrelated Gambian and Malawian adults. We generated 592 high-quality haplotypes by integrating family- and population-based reconstruction methods. RESULTS: We found 32 different haplotypes, of which 13 were shared between the two populations. Both populations were haplotypically diverse (gene diversity = 0.80, Gambia; 0.85, Malawi) and significantly differentiated (p < 10(-5 )by exact test). More than a quarter of marker pairs showed evidence of intragenic recombination (29% Gambia; 27% Malawi). We applied two new methods of analyzing haplotypic data: association efficiency analysis (AEA), which describes the ability of each SNP to detect every other SNP in a case-control scenario; and the entropy maximization method (EMM), which selects the subset of SNPs that most effectively dissects the underlying haplotypic structure. AEA revealed that many SNPs in TNF are poor markers of each other. The EMM showed that 8 of 12 SNPs (Gambia) and 7 of 12 SNPs (Malawi) are required to describe 95% of the haplotypic diversity. CONCLUSIONS: The TNF locus in the Gambian and Malawi sample is haplotypically diverse and has a rich history of intragenic recombination. As a consequence, a large proportion of TNF SNPs must be typed to detect a disease-modifying SNP at this locus. The most informative subset of SNPs to genotype differs between the two populations. BioMed Central 2003 2003-03-17 /pmc/articles/PMC154575/ /pubmed/12702205 http://dx.doi.org/10.1186/gb-2003-4-4-r24 Text en Copyright © 2003 Ackerman et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Ackerman, Hans Usen, Stanley Mott, Richard Richardson, Anna Sisay-Joof, Fatoumatta Katundu, Pauline Taylor, Terrie Ward, Ryk Molyneux, Malcolm Pinder, Margaret Kwiatkowski, Dominic P Haplotypic analysis of the TNF locus by association efficiency and entropy |
title | Haplotypic analysis of the TNF locus by association efficiency and entropy |
title_full | Haplotypic analysis of the TNF locus by association efficiency and entropy |
title_fullStr | Haplotypic analysis of the TNF locus by association efficiency and entropy |
title_full_unstemmed | Haplotypic analysis of the TNF locus by association efficiency and entropy |
title_short | Haplotypic analysis of the TNF locus by association efficiency and entropy |
title_sort | haplotypic analysis of the tnf locus by association efficiency and entropy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154575/ https://www.ncbi.nlm.nih.gov/pubmed/12702205 http://dx.doi.org/10.1186/gb-2003-4-4-r24 |
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