Genetic Architecture of Protein Expression and its Regulation in the Mouse Brain

Natural variation in protein expression is common in all organisms and contribute 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/6J (B6) and DBA/2J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and identified four common inheritance patterns, including dominant, additive, over- and under-dominant expression. We further applied the proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE).