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Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis

Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples c...

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Autores principales: Marsden, Clare Diana, Lee, Yoosook, Kreppel, Katharina, Weakley, Allison, Cornel, Anthony, Ferguson, Heather M., Eskin, Eleazar, Lanzaro, Gregory C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887528/
https://www.ncbi.nlm.nih.gov/pubmed/24281424
http://dx.doi.org/10.1534/g3.113.008326
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author Marsden, Clare Diana
Lee, Yoosook
Kreppel, Katharina
Weakley, Allison
Cornel, Anthony
Ferguson, Heather M.
Eskin, Eleazar
Lanzaro, Gregory C.
author_facet Marsden, Clare Diana
Lee, Yoosook
Kreppel, Katharina
Weakley, Allison
Cornel, Anthony
Ferguson, Heather M.
Eskin, Eleazar
Lanzaro, Gregory C.
author_sort Marsden, Clare Diana
collection PubMed
description Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples can result in spurious associations if not accounted for. As such, it is useful to have a detailed understanding of these factors before conducting association mapping experiments. Here we conducted whole-genome sequencing on 24 specimens of the malaria mosquito vector, Anopheles arabiensis, to further understanding of patterns of genetic diversity, population subdivision and linkage disequilibrium in this species. We found high levels of genetic diversity within the An. arabiensis genome, with ~800,000 high-confidence, single- nucleotide polymorphisms detected. However, levels of nucleotide diversity varied significantly both within and between chromosomes. We observed lower diversity on the X chromosome, within some inversions, and near centromeres. Population structure was absent at the local scale (Kilombero Valley, Tanzania) but detected between distant populations (Cameroon vs. Tanzania) where differentiation was largely restricted to certain autosomal chromosomal inversions such as 2Rb. Overall, linkage disequilibrium within An. arabiensis decayed very rapidly (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium was observed within some inversions, suggesting that recombination is reduced in those regions. The overall low levels of linkage disequilibrium suggests that association studies in this taxon will be very challenging for all but variants of large effect, and will require large sample sizes.
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spelling pubmed-38875282014-01-10 Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis Marsden, Clare Diana Lee, Yoosook Kreppel, Katharina Weakley, Allison Cornel, Anthony Ferguson, Heather M. Eskin, Eleazar Lanzaro, Gregory C. G3 (Bethesda) Investigations Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples can result in spurious associations if not accounted for. As such, it is useful to have a detailed understanding of these factors before conducting association mapping experiments. Here we conducted whole-genome sequencing on 24 specimens of the malaria mosquito vector, Anopheles arabiensis, to further understanding of patterns of genetic diversity, population subdivision and linkage disequilibrium in this species. We found high levels of genetic diversity within the An. arabiensis genome, with ~800,000 high-confidence, single- nucleotide polymorphisms detected. However, levels of nucleotide diversity varied significantly both within and between chromosomes. We observed lower diversity on the X chromosome, within some inversions, and near centromeres. Population structure was absent at the local scale (Kilombero Valley, Tanzania) but detected between distant populations (Cameroon vs. Tanzania) where differentiation was largely restricted to certain autosomal chromosomal inversions such as 2Rb. Overall, linkage disequilibrium within An. arabiensis decayed very rapidly (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium was observed within some inversions, suggesting that recombination is reduced in those regions. The overall low levels of linkage disequilibrium suggests that association studies in this taxon will be very challenging for all but variants of large effect, and will require large sample sizes. Genetics Society of America 2013-11-26 /pmc/articles/PMC3887528/ /pubmed/24281424 http://dx.doi.org/10.1534/g3.113.008326 Text en Copyright © 2014 Marsden et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Marsden, Clare Diana
Lee, Yoosook
Kreppel, Katharina
Weakley, Allison
Cornel, Anthony
Ferguson, Heather M.
Eskin, Eleazar
Lanzaro, Gregory C.
Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis
title Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis
title_full Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis
title_fullStr Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis
title_full_unstemmed Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis
title_short Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria Vector Anopheles arabiensis
title_sort diversity, differentiation, and linkage disequilibrium: prospects for association mapping in the malaria vector anopheles arabiensis
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887528/
https://www.ncbi.nlm.nih.gov/pubmed/24281424
http://dx.doi.org/10.1534/g3.113.008326
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