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Linkage disequilibrium interval mapping of quantitative trait loci
BACKGROUND: For many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559614/ https://www.ncbi.nlm.nih.gov/pubmed/16542433 http://dx.doi.org/10.1186/1471-2164-7-54 |
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author | Boitard, Simon Abdallah, Jihad de Rochambeau, Hubert Cierco-Ayrolles, Christine Mangin, Brigitte |
author_facet | Boitard, Simon Abdallah, Jihad de Rochambeau, Hubert Cierco-Ayrolles, Christine Mangin, Brigitte |
author_sort | Boitard, Simon |
collection | PubMed |
description | BACKGROUND: For many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed to deal with simply inherited disease traits. However, locating quantitative trait loci is statistically more challenging and considerable research is needed to provide robust and computationally efficient methods. RESULTS: Under a three-locus Wright-Fisher model, we derived approximate expressions for the expected haplotype frequencies in a population. We considered haplotypes comprising one trait locus and two flanking markers. Using these theoretical expressions, we built a likelihood-maximization method, called HAPim, for estimating the location of a quantitative trait locus. For each postulated position, the method only requires information from the two flanking markers. Over a wide range of simulation scenarios it was found to be more accurate than a two-marker composite likelihood method. It also performed as well as identity by descent methods, whilst being valuable in a wider range of populations. CONCLUSION: Our method makes efficient use of marker information, and can be valuable for fine mapping purposes. Its performance is increased if multiallelic markers are available. Several improvements can be developed to account for more complex evolution scenarios or provide robust confidence intervals for the location estimates. |
format | Text |
id | pubmed-1559614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-15596142006-09-11 Linkage disequilibrium interval mapping of quantitative trait loci Boitard, Simon Abdallah, Jihad de Rochambeau, Hubert Cierco-Ayrolles, Christine Mangin, Brigitte BMC Genomics Methodology Article BACKGROUND: For many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed to deal with simply inherited disease traits. However, locating quantitative trait loci is statistically more challenging and considerable research is needed to provide robust and computationally efficient methods. RESULTS: Under a three-locus Wright-Fisher model, we derived approximate expressions for the expected haplotype frequencies in a population. We considered haplotypes comprising one trait locus and two flanking markers. Using these theoretical expressions, we built a likelihood-maximization method, called HAPim, for estimating the location of a quantitative trait locus. For each postulated position, the method only requires information from the two flanking markers. Over a wide range of simulation scenarios it was found to be more accurate than a two-marker composite likelihood method. It also performed as well as identity by descent methods, whilst being valuable in a wider range of populations. CONCLUSION: Our method makes efficient use of marker information, and can be valuable for fine mapping purposes. Its performance is increased if multiallelic markers are available. Several improvements can be developed to account for more complex evolution scenarios or provide robust confidence intervals for the location estimates. BioMed Central 2006-03-16 /pmc/articles/PMC1559614/ /pubmed/16542433 http://dx.doi.org/10.1186/1471-2164-7-54 Text en Copyright © 2006 Boitard et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methodology Article Boitard, Simon Abdallah, Jihad de Rochambeau, Hubert Cierco-Ayrolles, Christine Mangin, Brigitte Linkage disequilibrium interval mapping of quantitative trait loci |
title | Linkage disequilibrium interval mapping of quantitative trait loci |
title_full | Linkage disequilibrium interval mapping of quantitative trait loci |
title_fullStr | Linkage disequilibrium interval mapping of quantitative trait loci |
title_full_unstemmed | Linkage disequilibrium interval mapping of quantitative trait loci |
title_short | Linkage disequilibrium interval mapping of quantitative trait loci |
title_sort | linkage disequilibrium interval mapping of quantitative trait loci |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559614/ https://www.ncbi.nlm.nih.gov/pubmed/16542433 http://dx.doi.org/10.1186/1471-2164-7-54 |
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