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

Autor: Alyssa Erickson, Suiping Zhou, Jie Luo, Ling Li, Xin Huang, Zachary Even, He Huang, Hai-Ming Xu, Junmin Peng, Lu Lu, Xusheng Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: BMC Genomics, Vol 22, Iss 1, Pp 1-12 (2021)
Druh dokumentu: article
ISSN: 1471-2164
DOI: 10.1186/s12864-021-08168-y
Popis: 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.
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