Genetic analysis of the mouse brain proteome.
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.
Klose
Joachim
J
Institut für Humangenetik, Humboldt-Universität zu Berlin, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany. joachim.klose@charite.de
Nock
Christina
C
Herrmann
Marion
M
Stühler
Kai
K
Marcus
Katrin
K
Blüggel
Martin
M
Krause
Eberhard
E
Schalkwyk
Leonard C
LC
Rastan
Sohaila
S
Brown
Steve D M
SD
Büssow
Konrad
K
Himmelbauer
Heinz
H
Lehrach
Hans
H
D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004247:DNA / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006579:Heterozygote; D013058:Mass Spectrometry; D051379:Mice; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D020033:Protein Isoforms
D005819:Genetic Markers; D020033:Protein Isoforms; D004247:DNA