Studying concomitantly both gene expression profiling and protein expression profiling

The “genome” comprises all the genes of a species, aligned in linear fashion along the chromosomes. One chromosome contains the “haploid genome” (about 3 x 109 nucleotides) Both chromosomes (all pairs of chromosomes) contain the “diploid genome” (~6 x 109 nucleotides). The sum of all transcribed DNA is the “transcriptome”, and the sum of all proteins––which should include all post-translational products as well––would be regarded as the “proteome”. A “quantitative trait locus” (QTL) is a segment of DNA (the ‘locus’) that correlates with variation in a phenotype (the quantitative trait’). Typically, the QTL is linked to, or contains, those genes that control that phenotype.

Genetic variation modulates protein expression through both transcriptional and post-transcriptional mechanisms. To characterize the consequences of natural genetic diversity on the proteome, authors [attached article] combined a multiplexed mass spectrometry-based method for protein quantification with an emerging outbred mouse model containing extensive genetic variation from eight inbred founder strains. By measuring genome-wide transcript and protein expression in liver from the “192-Diversity Outbred Mouse” Project, they identified 2,866 protein quantitative trait loci (pQTL) with twice as many local (cis), as distant (trans), genetic variants. These data support distinct transcriptional and post-transcriptional models underlying the observed pQTL effects. Using a sensitive approach to mediation analysis, authors were often able to identify a second protein or transcript as causal mediator of a distant pQTL. Their analysis reveals an extensive network of direct protein–protein interactions. Lastly, authors show that local genotype can provide accurate predictions of protein abundance in an independent cohort of the collaborative-cross mice.

Nature  23 June 2o16; 534: 500–505

This entry was posted in Center for Environmental Genetics. Bookmark the permalink.