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Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross

BACKGROUND: A powerful way to identify genes for complex traits it to combine genetic and genomic methods. Many trait quantitative trait loci (QTLs) for complex traits are sex specific, but the reason for this is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: RNA was prepared from bone marrow...

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Autores principales: Bhasin, Jeffrey M., Chakrabarti, Enakshi, Peng, Dao-Quan, Kulkarni, Aneesh, Chen, Xi, Smith, Jonathan D.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174529/
https://www.ncbi.nlm.nih.gov/pubmed/18197246
http://dx.doi.org/10.1371/journal.pone.0001435
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author Bhasin, Jeffrey M.
Chakrabarti, Enakshi
Peng, Dao-Quan
Kulkarni, Aneesh
Chen, Xi
Smith, Jonathan D.
author_facet Bhasin, Jeffrey M.
Chakrabarti, Enakshi
Peng, Dao-Quan
Kulkarni, Aneesh
Chen, Xi
Smith, Jonathan D.
author_sort Bhasin, Jeffrey M.
collection PubMed
description BACKGROUND: A powerful way to identify genes for complex traits it to combine genetic and genomic methods. Many trait quantitative trait loci (QTLs) for complex traits are sex specific, but the reason for this is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: RNA was prepared from bone marrow derived macrophages of 93 female and 114 male F(2) mice derived from a strain intercross between apoE-deficient mice on the AKR and DBA/2 genetic backgrounds, and was subjected to transcriptome profiling using microarrays. A high density genome scan was performed using a mouse SNP chip, and expression QTLs (eQTLs) were located for expressed transcripts. Using suggestive and significant LOD score cutoffs of 3.0 and 4.3, respectively, thousands of eQTLs in the female and male cohorts were identified. At the suggestive LOD threshold the majority of the eQTLs were trans eQTLs, mapping unlinked to the position of the gene. Cis eQTLs, which mapped to the location of the gene, had much higher LOD scores than trans eQTLs, indicating their more direct effect on gene expression. The majority of cis eQTLs were common to both males and females, but only ∼1% of the trans eQTLs were shared by both sexes. At the significant LOD threshold, the majority of eQTLs were cis eQTLs, which were mostly sex-shared, while the trans eQTLs were overwhelmingly sex-specific. Pooling the male and female data, 31% of expressed transcripts were expressed at different levels in males vs. females after correction for multiple testing. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate a large sex effect on gene expression and trans regulation, under conditions where male and female derived cells were cultured ex vivo and thus without the influence of endogenous sex steroids. These data suggest that eQTL data from male and female mice should be analyzed separately, as many effects, such as trans regulation are sex specific.
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spelling pubmed-21745292008-01-16 Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross Bhasin, Jeffrey M. Chakrabarti, Enakshi Peng, Dao-Quan Kulkarni, Aneesh Chen, Xi Smith, Jonathan D. PLoS One Research Article BACKGROUND: A powerful way to identify genes for complex traits it to combine genetic and genomic methods. Many trait quantitative trait loci (QTLs) for complex traits are sex specific, but the reason for this is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: RNA was prepared from bone marrow derived macrophages of 93 female and 114 male F(2) mice derived from a strain intercross between apoE-deficient mice on the AKR and DBA/2 genetic backgrounds, and was subjected to transcriptome profiling using microarrays. A high density genome scan was performed using a mouse SNP chip, and expression QTLs (eQTLs) were located for expressed transcripts. Using suggestive and significant LOD score cutoffs of 3.0 and 4.3, respectively, thousands of eQTLs in the female and male cohorts were identified. At the suggestive LOD threshold the majority of the eQTLs were trans eQTLs, mapping unlinked to the position of the gene. Cis eQTLs, which mapped to the location of the gene, had much higher LOD scores than trans eQTLs, indicating their more direct effect on gene expression. The majority of cis eQTLs were common to both males and females, but only ∼1% of the trans eQTLs were shared by both sexes. At the significant LOD threshold, the majority of eQTLs were cis eQTLs, which were mostly sex-shared, while the trans eQTLs were overwhelmingly sex-specific. Pooling the male and female data, 31% of expressed transcripts were expressed at different levels in males vs. females after correction for multiple testing. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate a large sex effect on gene expression and trans regulation, under conditions where male and female derived cells were cultured ex vivo and thus without the influence of endogenous sex steroids. These data suggest that eQTL data from male and female mice should be analyzed separately, as many effects, such as trans regulation are sex specific. Public Library of Science 2008-01-16 /pmc/articles/PMC2174529/ /pubmed/18197246 http://dx.doi.org/10.1371/journal.pone.0001435 Text en Bhasin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhasin, Jeffrey M.
Chakrabarti, Enakshi
Peng, Dao-Quan
Kulkarni, Aneesh
Chen, Xi
Smith, Jonathan D.
Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross
title Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross
title_full Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross
title_fullStr Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross
title_full_unstemmed Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross
title_short Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross
title_sort sex specific gene regulation and expression qtls in mouse macrophages from a strain intercross
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174529/
https://www.ncbi.nlm.nih.gov/pubmed/18197246
http://dx.doi.org/10.1371/journal.pone.0001435
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