Treatment- and population-dependent activity patterns of behavioral and expression QTLs.

Genetic control of gene expression and higher-order phenotypes is almost invariably dependent on environment and experimental conditions. We use two families of recombinant inbred strains of mice (LXS and BXD) to study treatment- and genotype-dependent control of hippocampal gene expression and beha...

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Main Authors: Jesse D Ziebarth, Melloni N Cook, Xusheng Wang, Robert W Williams, Lu Lu, Yan Cui
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359631/?tool=EBI
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author Jesse D Ziebarth
Melloni N Cook
Xusheng Wang
Robert W Williams
Lu Lu
Yan Cui
author_facet Jesse D Ziebarth
Melloni N Cook
Xusheng Wang
Robert W Williams
Lu Lu
Yan Cui
author_sort Jesse D Ziebarth
collection DOAJ
description Genetic control of gene expression and higher-order phenotypes is almost invariably dependent on environment and experimental conditions. We use two families of recombinant inbred strains of mice (LXS and BXD) to study treatment- and genotype-dependent control of hippocampal gene expression and behavioral phenotypes. We analyzed responses to all combinations of two experimental perturbations, ethanol and restraint stress, in both families, allowing for comparisons across 8 combinations of treatment and population. We introduce the concept of QTL activity patterns to characterize how associations between genomic loci and traits vary across treatments. We identified several significant behavioral QTLs and many expression QTLs (eQTLs). The behavioral QTLs are highly dependent on treatment and population. We classified eQTLs into three groups: cis-eQTLs (expression variation that maps to within 5 Mb of the cognate gene), syntenic trans-eQTLs (the gene and the QTL are on the same chromosome but not within 5 Mb), and non-syntenic trans-eQTLs (the gene and the QTL are on different chromosomes). We found that most non-syntenic trans-eQTLs were treatment-specific whereas both classes of syntenic eQTLs were more conserved across treatments. We also found there was a correlation between regions along the genome enriched for eQTLs and SNPs that were conserved across the LXS and BXD families. Genes with eQTLs that co-localized with the behavioral QTLs and displayed similar QTL activity patterns were identified as potential candidate genes associated with the phenotypes, yielding identification of novel genes as well as genes that have been previously associated with responses to ethanol.
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spelling doaj.art-80ea68498bb64f48af3131e52e8e04b52022-12-21T20:34:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3180510.1371/journal.pone.0031805Treatment- and population-dependent activity patterns of behavioral and expression QTLs.Jesse D ZiebarthMelloni N CookXusheng WangRobert W WilliamsLu LuYan CuiGenetic control of gene expression and higher-order phenotypes is almost invariably dependent on environment and experimental conditions. We use two families of recombinant inbred strains of mice (LXS and BXD) to study treatment- and genotype-dependent control of hippocampal gene expression and behavioral phenotypes. We analyzed responses to all combinations of two experimental perturbations, ethanol and restraint stress, in both families, allowing for comparisons across 8 combinations of treatment and population. We introduce the concept of QTL activity patterns to characterize how associations between genomic loci and traits vary across treatments. We identified several significant behavioral QTLs and many expression QTLs (eQTLs). The behavioral QTLs are highly dependent on treatment and population. We classified eQTLs into three groups: cis-eQTLs (expression variation that maps to within 5 Mb of the cognate gene), syntenic trans-eQTLs (the gene and the QTL are on the same chromosome but not within 5 Mb), and non-syntenic trans-eQTLs (the gene and the QTL are on different chromosomes). We found that most non-syntenic trans-eQTLs were treatment-specific whereas both classes of syntenic eQTLs were more conserved across treatments. We also found there was a correlation between regions along the genome enriched for eQTLs and SNPs that were conserved across the LXS and BXD families. Genes with eQTLs that co-localized with the behavioral QTLs and displayed similar QTL activity patterns were identified as potential candidate genes associated with the phenotypes, yielding identification of novel genes as well as genes that have been previously associated with responses to ethanol.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359631/?tool=EBI
spellingShingle Jesse D Ziebarth
Melloni N Cook
Xusheng Wang
Robert W Williams
Lu Lu
Yan Cui
Treatment- and population-dependent activity patterns of behavioral and expression QTLs.
PLoS ONE
title Treatment- and population-dependent activity patterns of behavioral and expression QTLs.
title_full Treatment- and population-dependent activity patterns of behavioral and expression QTLs.
title_fullStr Treatment- and population-dependent activity patterns of behavioral and expression QTLs.
title_full_unstemmed Treatment- and population-dependent activity patterns of behavioral and expression QTLs.
title_short Treatment- and population-dependent activity patterns of behavioral and expression QTLs.
title_sort treatment and population dependent activity patterns of behavioral and expression qtls
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359631/?tool=EBI
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AT robertwwilliams treatmentandpopulationdependentactivitypatternsofbehavioralandexpressionqtls
AT lulu treatmentandpopulationdependentactivitypatternsofbehavioralandexpressionqtls
AT yancui treatmentandpopulationdependentactivitypatternsofbehavioralandexpressionqtls