Genetics of natural variation in human gene expression
This project focuses on the genetics of variation in human gene expression. Previously, we found abundant natural variation in expression level and evidence of a genetic contribution to this variation (Cheung et al. 2003). We are performing genetic analyses to identify the determinants of this variation (Morley et al, 2004; Cheung et al, 2005).
We have measured the expression levels of several thousand genes in lymphoblasts of members of the CEPH families. We treated the expression levels as quantitative traits, and carried out genome-wide linkage analyses to determine the chromosomal locations linked to these expression phenotypes. Initial results showed significant evidence of linkage for about 1,000 expression phenotypes (p < 3.7 x 10-5 (lod 3.4)). Among them, some have evidence of linkage far beyond this threshold. We examined the chromosomal regions that are linked to the expression levels of the ~1,000 phenotypes. We found that the majority of them (> 70%) act in trans, and that many genes have multiple regulators (QTLs) of expression.
To confirm and narrow the regulatory regions identified by the linkage analyses, we are performing whole genome and regional association analyses. In addition, we are performing molecular studies to characterize the transcriptional regulators.
In this presentation, I will show data from these analyses and describe the global landscape of variation in gene expression and transcriptional control in the human genome.