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Genetic modulation of protein expression in rat brain
Ling Li1,2, Zhiping Wu3,4, Andrea Guarracino2,5
1Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Iscience
|March 24, 2025
Summary
This study analyzed brain protein expression in rats, identifying genetic links to complex traits. Findings reveal how protein variations influence brain function and disease susceptibility.
Area of Science:
- Neuroscience
- Genetics
- Proteomics
Background:
- Genetic variations influence protein expression, impacting common diseases and complex traits.
- Protein expression is less explored than mRNA or classical phenotypes in genetic studies.
Purpose of the Study:
- To systematically analyze brain proteomes in a rat family to understand genetic modulation of protein expression.
- To identify proteins with differential expression and link them to genetic loci.
- To explore connections between rat protein quantitative trait loci (pQTLs) and human disorders.
Main Methods:
- Tandem mass tag (TMT)-based quantitative mass spectrometry was used to analyze brain proteomes.
- Proteins were quantified across parental and recombinant inbred (RI) rat strains.
- Proteogenomics and sex-specific analyses were employed to identify variant peptides and cis-pQTLs.
Main Results:
- Quantified 8,119 proteins, identifying 597 with differential expression and 464 linked to cis-acting quantitative trait loci (pQTLs).
- Identified 95 variant peptides through proteogenomics.
- Revealed shared and distinct cis-pQTLs between sexes and improved candidate gene identification using the rat pangenome.
Conclusions:
- Large-scale proteo-genetic datasets are valuable for understanding brain protein modulation.
- This study enhances the ability to pinpoint candidate genes for pQTLs.
- Findings contribute to elucidating the links between protein variations in the brain and complex central nervous system (CNS) traits.
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