Genetic architecture of protein expression and its regulation in the mouse brain

Abstract Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein exp...

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Autores principales: Alyssa Erickson, Suiping Zhou, Jie Luo, Ling Li, Xin Huang, Zachary Even, He Huang, Hai-Ming Xu, Junmin Peng, Lu Lu, Xusheng Wang
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Lenguaje:EN
Publicado: BMC 2021
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Acceso en línea:https://doaj.org/article/60239a5d9557496f9d1f68c754dfb8a5
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spelling oai:doaj.org-article:60239a5d9557496f9d1f68c754dfb8a52021-12-05T12:17:17ZGenetic architecture of protein expression and its regulation in the mouse brain10.1186/s12864-021-08168-y1471-2164https://doaj.org/article/60239a5d9557496f9d1f68c754dfb8a52021-12-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08168-yhttps://doaj.org/toc/1471-2164Abstract Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6 J (B6) and DBA/2 J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. Results By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and characterized the genetic basis of protein expression. We further applied a proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis-effects and 17 variant peptides showing trans-effects. Comparison of regulation at transcript and protein levels show a significant divergence. Conclusions The results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans-acting regulatory differences to protein expression.Alyssa EricksonSuiping ZhouJie LuoLing LiXin HuangZachary EvenHe HuangHai-Ming XuJunmin PengLu LuXusheng WangBMCarticleProteomeMouseBrainProtein expressionAllele-specific expressionProtein regulationBiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Proteome
Mouse
Brain
Protein expression
Allele-specific expression
Protein regulation
Biotechnology
TP248.13-248.65
Genetics
QH426-470
spellingShingle Proteome
Mouse
Brain
Protein expression
Allele-specific expression
Protein regulation
Biotechnology
TP248.13-248.65
Genetics
QH426-470
Alyssa Erickson
Suiping Zhou
Jie Luo
Ling Li
Xin Huang
Zachary Even
He Huang
Hai-Ming Xu
Junmin Peng
Lu Lu
Xusheng Wang
Genetic architecture of protein expression and its regulation in the mouse brain
description Abstract Background Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6 J (B6) and DBA/2 J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. Results By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and characterized the genetic basis of protein expression. We further applied a proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis-effects and 17 variant peptides showing trans-effects. Comparison of regulation at transcript and protein levels show a significant divergence. Conclusions The results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans-acting regulatory differences to protein expression.
format article
author Alyssa Erickson
Suiping Zhou
Jie Luo
Ling Li
Xin Huang
Zachary Even
He Huang
Hai-Ming Xu
Junmin Peng
Lu Lu
Xusheng Wang
author_facet Alyssa Erickson
Suiping Zhou
Jie Luo
Ling Li
Xin Huang
Zachary Even
He Huang
Hai-Ming Xu
Junmin Peng
Lu Lu
Xusheng Wang
author_sort Alyssa Erickson
title Genetic architecture of protein expression and its regulation in the mouse brain
title_short Genetic architecture of protein expression and its regulation in the mouse brain
title_full Genetic architecture of protein expression and its regulation in the mouse brain
title_fullStr Genetic architecture of protein expression and its regulation in the mouse brain
title_full_unstemmed Genetic architecture of protein expression and its regulation in the mouse brain
title_sort genetic architecture of protein expression and its regulation in the mouse brain
publisher BMC
publishDate 2021
url https://doaj.org/article/60239a5d9557496f9d1f68c754dfb8a5
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