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Health

Two papers in Nature Genetics on gene expression

Gene ExpressionBy Razib KhanSeptember 17, 2007 7:57 PM

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A genome-wide association study of global gene expression:

We found that 15,084 transcripts (28%) representing 6,660 genes had narrow-sense heritabilities (H^2) > 0.3. We executed genome-wide association scans for these traits and found peak lod scores between 3.68 and 59.1. The most highly heritable traits were markedly enriched in Gene Ontology descriptors for response to unfolded protein (chaperonins and heat shock proteins), regulation of progression through the cell cycle, RNA processing, DNA repair, immune responses and apoptosis. SNPs that regulate expression of these genes are candidates in the study of degenerative diseases, malignancy, infection and inflammation. We have created a downloadable database to facilitate use of our findings in the mapping of complex disease loci.

And, Population genomics of human gene expression:

Genetic variation influences gene expression, and this variation in gene expression can be efficiently mapped to specific genomic regions and variants...We find that gene expression is heritable and that differentiation between populations is in agreement with earlier small-scale studies. A detailed association analysis of over 2.2 million common SNPs per population (5% frequency in HapMap) with gene expression identified at least 1,348 genes with association signals in cis and at least 180 in trans. Replication in at least one independent population was achieved for 37% of cis signals and 15% of trans signals, respectively.

Our results strongly support an abundance of cis-regulatory variation in the human genome

. Detection of trans effects is limited but suggests that regulatory variation may be the key primary effect contributing to phenotypic variation in humans. We also explore several methodologies that improve the current state of analysis of gene expression variation. You can read about the debate about cis-regulatory changes at evolgen.

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