Quantitative Trait Loci Mapping of the Mouse Plasma Proteome (pQTL)
Open accessAbstract
A current challenge in the era of genome-wide studies is to determine the responsible genes and mechanisms underlying newly identified loci. Screening of the plasma proteome by high-throughput mass spectrometry (MALDI-TOF MS) is considered a promising approach for identification of metabolic and disease processes. Therefore, plasma proteome screening might be particularly useful for identifying responsible genes when combined with analysis of variation in the genome. Here, we describe a proteomic quantitative trait locus (pQTL) study of plasma proteome screens in an F2 intercross of 455 mice mapped with 177 genetic markers across the genome. A total of 69 of 176 peptides revealed significant LOD scores (≥5.35) demonstrating strong genetic regulation of distinct components of the plasma proteome. Analyses were confirmed by mechanistic studies and MALDI-TOF/TOF, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the two strongest pQTLs: A pQTL for mass-to-charge ratio (m/z) 3494 (LOD 24.9, D11Mit151) was identified as the N-terminal 35 amino acids of hemoglobin subunit A (Hba) and caused by genetic variation in Hba. Another pQTL for m/z 8713 (LOD 36.4; D1Mit111) was caused by variation in apolipoprotein A2 (Apoa2) and cosegregated with HDL cholesterol. Taken together, we show that genome-wide plasma proteome profiling in combination with genome-wide genetic screening aids in the identification of causal genetic variants affecting abundance of plasma proteins.
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Recent pQTL analyses using precise MS measurement over many samples revealed complex genetic influence on protein levels in yeast and mouse.
“Using precise MS measurement of peptides over a large number of samples, recent pQTL analyses revealed complex genetic influence on the levels of proteins in yeast (Picotti et al., 2013) and mouse (Holdt et al., 2013).”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as Holdt et al., 2013
A pQTL analysis of mouse plasma identified strong genetic determinants for approximately 40% of tested proteins and suggested causal genetic variants affecting plasma protein abundance.
“The pQTL analysis of mouse plasma identified strong genetic determinants for approximately 40% of tested proteins, and suggested causal genetic variants affecting abundance of plasma proteins (Holdt et al., 2013).”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as Holdt et al., 2013
QTL have been extensively mapped to complex traits using transcriptomics (eQTL), and more recently variants have been related to protein abundance (pQTL).
“Quantitative trait loci (QTL) have been extensively mapped to a variety of complex traits using transcriptomics in terms of the relationship between genomic variants and RNA expression (eQTL) and, more recently, variants have also been related to protein abundance (pQTL)87.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [87]
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- Authors
- Holdt, L. M., von Delft, A., Nicolaou, A., Baumann, S., Kostrzewa, M., Thiery, J., & Teupser, D.
- Affiliations
- University Hospital Leipzig (DE)
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany
- Bruker (Germany) (DE)
- Corresponding author
- Teupser, Daniel
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-01
- Volume
- 193
- Issue
- 2
- Pages
- 601-608
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC3567747
- OpenAlex
- W2158973708
- Cited by
- 18
- References
- 2
- Citations by year
- 2023: 1 · 2022: 2 · 2020: 1 · 2019: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- plasma proteome, apolipoprotein A-II, HDL cholesterol, F2 intercross, genetic markers, causal variants
- MeSH terms
- Animals, Crosses, Genetic, Genetic Markers, Hemoglobin A, Cholesterol, HDL, Mice, Inbred C57BL, Molecular Weight, Genetic Variation, Apolipoprotein A-II, Protein Structure, Tertiary, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Proteome, Quantitative Trait Loci, Mice, Static Electricity
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