Genetic basis of proteome variation in yeast.
Proper regulation of protein levels is essential for health, and abnormal levels of proteins are hallmarks of many diseases. A number of studies have recently shown that messenger RNA levels vary among individuals of a species and that genetic linkage analysis can be used to identify quantitative trait loci that influence these levels. By contrast, little is known about the genetic basis of variation in protein levels in genetically diverse populations, in large part because techniques for large-scale measurements of protein abundance lag far behind those for measuring transcript abundance. Here we describe a label-free, mass spectrometry-based approach to measuring protein levels in total unfractionated cellular proteins, and we apply this approach to elucidate the genetic basis of variation in protein abundance in a cross between two diverse strains of yeast. Loci that influenced protein abundance differed from those that influenced transcript levels, emphasizing the importance of direct analysis of the proteome.
Foss
Eric J
EJ
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Radulovic
Dragan
D
Shaffer
Scott A
SA
Ruderfer
Douglas M
DM
Bedalov
Antonio
A
Goodlett
David R
DR
Kruglyak
Leonid
L
D015153:Blotting, Western; D002853:Chromatography, Liquid; D015825:Chromosomes, Fungal / Q000235:genetics; D020869:Gene Expression Profiling; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation; D020543:Proteome / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005819:Genetic Markers; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins