Nature Genetics30, 385 - 393 (2002)
Published online: 25 March 2002; | doi:10.1038/ng861
Genetic analysis of the mouse brain proteome
Joachim Klose1, Christina Nock1, 2, 3, Marion Herrmann1, Kai Stühler4, Katrin Marcus4, Martin Blüggel5, Eberhard Krause6, Leonard C. Schalkwyk7, Sohaila Rastan8, Steve D.M. Brown9, Konrad Büssow3, Heinz Himmelbauer3
& Hans Lehrach3
1
Institut für Humangenetik, Humboldt-Universität zu Berlin, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany.
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.
