Polymorphic cis- and trans-regulation of human gene expression

Area of Science:

• Genomics
• Human Genetics
• Gene Regulation

Background:

• Human gene expression levels exhibit significant individual variation.
• This variation can be leveraged as a quantitative phenotype in genetic studies to identify gene regulators.
• Genome-wide scans can reveal regulatory mechanisms without prior assumptions.

Purpose of the Study:

• To conduct genetic analyses in a large sample size to identify cis- and trans-acting polymorphic regulators of human gene expression.
• To characterize previously unknown regulatory relationships and mechanisms.
• To enhance the resolution of polymorphic gene expression regulation analysis.

Main Methods:

• Genome-wide genetic analyses utilizing expression levels as quantitative phenotypes.
• Validation of cis-acting regulators via RNA-Seq and differential allelic expression.
• Validation of trans-regulators through gene knockdown, metabolic assays, and chromosome conformation capture (3C).

Main Results:

• Identification of cis- and trans-acting polymorphic regulators for approximately 1,000 human genes.
• The majority of identified regulators act in trans to their target genes.
• A significant proportion of these trans-regulators were previously unrecognized for their role in gene expression regulation.

Conclusions:

• Polymorphic variation significantly influences human gene expression through both cis- and trans-acting regulators.
• This study identified a substantial number of novel gene expression regulators, particularly in trans.
• The findings provide a higher resolution characterization of polymorphic gene expression regulation, enabling new avenues for research.