Genome Technology Center

Contrasting genetic regulation of the proteome and the transcriptome

Eric Foss
Fred Hutchinson Cancer Research Center

In recent years there have been an enormous number of studies aimed at understanding how the genetic diversity in naturally occurring populations manifests itself in variation in the levels of thousands of transcripts. However, if changes in transcript levels are to have important biological consequences, they must lead to changes in protein levels. Little is known about the extent to which variation in transcript levels in naturally occurring populations implies variation in protein levels, largely because techniques for comparative analysis of the proteomes of large numbers of individuals do not exist.
We have developed a mathematical approach to mass spectrometry-based protein quantitation that allows us to compare the proteomes of large numbers of individuals, and we have applied this technology in a genetically diverse population of yeast. We find that for most genes, transcript levels show little correlation with protein levels, and we have used genetic mapping to dissect the biology underlying this observation. I will discuss this work and also describe how we are using these insights and this technology to find clinically useful protein biomarkers in acute leukemia.

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