Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies.
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http://dx.doi.org/10.1038/ng861 | DOI Listing |
Science
January 2025
Center for Pulmonary Vascular Biology and Medicine, Pittsburgh, Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.
View Article and Find Full Text PDFPLoS One
January 2025
Cancer Center, Kagoshima University Hospital, Kagoshima, Japan.
Kinase-related gene fusion and point mutations play pivotal roles as drivers in cancer, necessitating optimized, targeted therapy against these alterations. The efficacy of molecularly targeted therapeutics varies depending on the specific alteration, with great success reported for such therapeutics in the treatment of cancer with kinase fusion proteins. However, the involvement of actionable alterations in solid tumors, especially regarding kinase fusions, remains unclear.
View Article and Find Full Text PDFAnn Med
December 2025
Department of General Practice, Hainan affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, China.
Background: Although existing studies have identified some genetic loci associated with chronic obstructive pulmonary disease (COPD) susceptibility, many variants remain to be discovered. The aim of this study was to further explore the potential relationship between single nucleotide polymorphisms (SNPs) and COPD risk.
Methods: Nine hundred and ninety-six subjects were recruited (498 COPD cases and 498 healthy controls).
Int J Epidemiol
December 2024
International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France.
Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.
Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.
Front Cell Infect Microbiol
January 2025
Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Background: The vitamin D pathway contributes to the microbicidal activity of macrophages against infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to evaluate single-nucleotide polymorphisms (SNPs) in the components of the vitamin D pathway and associated cytokine genes that could be related to resistance or susceptibility to American tegumentary leishmaniasis (ATL).
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