Genetic Modulation of Protein Expression in Rat Brain

• DOI: 10.1101/2024.02.17.580840
• Publication Date: 2024-02-27T18:08:14Z
• Authors: Ling Li; Zhiping Wu; Andrea Guarracino; Flavia Villani; Deihui Kong; Ariana Mancieri; Aijun Zhang; Laura Saba; Hao Chen; Hana Brozka; Karel Vales; Anna N. Senko; Gerd Kempermann; Ales Stuchlik; Michal Pravenec; Pjotr Prins; Junmin Peng; Robert W. Williams; Xusheng Wang
• Keywords: Proteome; Proteogenomics; Genetic linkage; Genetic architecture

Abstract Genetic variations in protein expression are implicated a broad spectrum of common diseases and complex traits. However, the fundamental genetic architecture variation have received comparatively less attention than either mRNA or classical phenotypes. In this study, we systematically quantified proteins brains large family rats using tandem mass tag (TMT)-based quantitative mass-spectrometry (MS) technology. We identified comprehensive proteome 8,119 from Spontaneously Hypertensive (SHR/Olalpcv), Brown Norway with polydactyly-luxate (BN-Lx/Cub), 29 their fully inbred HXB/BXH progeny. Differential (DE) analysis 597 significant differences between parental strains (fold change > 2 FDR < 0.01). characterized 95 variant peptides by proteogenomics approach discovered 464 linked to strong cis -acting trait loci (pQTLs, 0.05). also explored linkage pQTLs behavioral phenotypes examined sex-specific reveal both distinct shared -pQTLs sexes. Furthermore, creating novel view rat pangenome, improved ability pinpoint candidate genes underlying pQTL. Finally, connection human disorders, underscoring translational potential our findings. Collectively, work demonstrates value systematic proteo-genetic datasets understanding modulation brain its functional central nervous system (CNS)