Integrative analysis of low- and high-resolution eQTL.

The study of expression quantitative trait loci (eQTL) is a powerful way of detecting transcriptional regulators at a genomic scale and for elucidating how natural genetic variation impacts gene expression. Power and genetic resolution are heavily affected by the study population: whereas recombinan...

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Autores principales:	Salvatore Loguercio, Rupert W Overall, Jacob J Michaelson, Tim Wiltshire, Mathew T Pletcher, Brooke H Miller, John R Walker, Gerd Kempermann, Andrew I Su, Andreas Beyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1e6da615c0c494e9bd37ca5ba88ea12
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spelling	oai:doaj.org-article:e1e6da615c0c494e9bd37ca5ba88ea122021-11-18T07:36:59ZIntegrative analysis of low- and high-resolution eQTL.1932-620310.1371/journal.pone.0013920https://doaj.org/article/e1e6da615c0c494e9bd37ca5ba88ea122010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21085707/?tool=EBIhttps://doaj.org/toc/1932-6203The study of expression quantitative trait loci (eQTL) is a powerful way of detecting transcriptional regulators at a genomic scale and for elucidating how natural genetic variation impacts gene expression. Power and genetic resolution are heavily affected by the study population: whereas recombinant inbred (RI) strains yield greater statistical power with low genetic resolution, using diverse inbred or outbred strains improves genetic resolution at the cost of lower power. In order to overcome the limitations of both individual approaches, we combine data from RI strains with genetically more diverse strains and analyze hippocampus eQTL data obtained from mouse RI strains (BXD) and from a panel of diverse inbred strains (Mouse Diversity Panel, MDP). We perform a systematic analysis of the consistency of eQTL independently obtained from these two populations and demonstrate that a significant fraction of eQTL can be replicated. Based on existing knowledge from pathway databases we assess different approaches for using the high-resolution MDP data for fine mapping BXD eQTL. Finally, we apply this framework to an eQTL hotspot on chromosome 1 (Qrr1), which has been implicated in a range of neurological traits. Here we present the first systematic examination of the consistency between eQTL obtained independently from the BXD and MDP populations. Our analysis of fine-mapping approaches is based on 'real life' data as opposed to simulated data and it allows us to propose a strategy for using MDP data to fine map BXD eQTL. Application of this framework to Qrr1 reveals that this eQTL hotspot is not caused by just one (or few) 'master regulators', but actually by a set of polymorphic genes specific to the central nervous system.Salvatore LoguercioRupert W OverallJacob J MichaelsonTim WiltshireMathew T PletcherBrooke H MillerJohn R WalkerGerd KempermannAndrew I SuAndreas BeyerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e13920 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Salvatore Loguercio Rupert W Overall Jacob J Michaelson Tim Wiltshire Mathew T Pletcher Brooke H Miller John R Walker Gerd Kempermann Andrew I Su Andreas Beyer Integrative analysis of low- and high-resolution eQTL.
description	The study of expression quantitative trait loci (eQTL) is a powerful way of detecting transcriptional regulators at a genomic scale and for elucidating how natural genetic variation impacts gene expression. Power and genetic resolution are heavily affected by the study population: whereas recombinant inbred (RI) strains yield greater statistical power with low genetic resolution, using diverse inbred or outbred strains improves genetic resolution at the cost of lower power. In order to overcome the limitations of both individual approaches, we combine data from RI strains with genetically more diverse strains and analyze hippocampus eQTL data obtained from mouse RI strains (BXD) and from a panel of diverse inbred strains (Mouse Diversity Panel, MDP). We perform a systematic analysis of the consistency of eQTL independently obtained from these two populations and demonstrate that a significant fraction of eQTL can be replicated. Based on existing knowledge from pathway databases we assess different approaches for using the high-resolution MDP data for fine mapping BXD eQTL. Finally, we apply this framework to an eQTL hotspot on chromosome 1 (Qrr1), which has been implicated in a range of neurological traits. Here we present the first systematic examination of the consistency between eQTL obtained independently from the BXD and MDP populations. Our analysis of fine-mapping approaches is based on 'real life' data as opposed to simulated data and it allows us to propose a strategy for using MDP data to fine map BXD eQTL. Application of this framework to Qrr1 reveals that this eQTL hotspot is not caused by just one (or few) 'master regulators', but actually by a set of polymorphic genes specific to the central nervous system.
format	article
author	Salvatore Loguercio Rupert W Overall Jacob J Michaelson Tim Wiltshire Mathew T Pletcher Brooke H Miller John R Walker Gerd Kempermann Andrew I Su Andreas Beyer
author_facet	Salvatore Loguercio Rupert W Overall Jacob J Michaelson Tim Wiltshire Mathew T Pletcher Brooke H Miller John R Walker Gerd Kempermann Andrew I Su Andreas Beyer
author_sort	Salvatore Loguercio
title	Integrative analysis of low- and high-resolution eQTL.
title_short	Integrative analysis of low- and high-resolution eQTL.
title_full	Integrative analysis of low- and high-resolution eQTL.
title_fullStr	Integrative analysis of low- and high-resolution eQTL.
title_full_unstemmed	Integrative analysis of low- and high-resolution eQTL.
title_sort	integrative analysis of low- and high-resolution eqtl.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/e1e6da615c0c494e9bd37ca5ba88ea12
work_keys_str_mv	AT salvatoreloguercio integrativeanalysisoflowandhighresolutioneqtl AT rupertwoverall integrativeanalysisoflowandhighresolutioneqtl AT jacobjmichaelson integrativeanalysisoflowandhighresolutioneqtl AT timwiltshire integrativeanalysisoflowandhighresolutioneqtl AT mathewtpletcher integrativeanalysisoflowandhighresolutioneqtl AT brookehmiller integrativeanalysisoflowandhighresolutioneqtl AT johnrwalker integrativeanalysisoflowandhighresolutioneqtl AT gerdkempermann integrativeanalysisoflowandhighresolutioneqtl AT andrewisu integrativeanalysisoflowandhighresolutioneqtl AT andreasbeyer integrativeanalysisoflowandhighresolutioneqtl
_version_	1718423194451312640

Integrative analysis of low- and high-resolution eQTL.

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