Influence of human genome polymorphism on gene expression.

Area of Science:

• Genomics
• Systems Biology
• Human Genetics

Background:

• Genetic variation significantly impacts gene expression, leading to phenotypic diversity and disease susceptibility.
• Large-scale studies increasingly integrate genomic variation data with gene expression (genetical genomics).
• Expression quantitative trait mapping has been a focus of recent reviews, emphasizing statistical considerations.

Purpose of the Study:

• To review allele-specific expression studies in human samples.
• To discuss study design and sources of variation for mapping human cis-acting regulatory variation.
• To assess the feasibility of studying trans-acting variation in the human genome.

Main Methods:

• Comparative analysis of allele-specific expression studies.
• Review of existing literature on genetical genomics and expression quantitative traits.
• Discussion of challenges in obtaining large human tissue panels.

Main Results:

• Human lymphoblastoid cell lines from the CEPH HapMap panel are primary resources for allele-specific expression studies.
• Mapping cis-acting regulatory variation requires detailed study designs and consideration of variation sources.
• Current knowledge is insufficient for comprehensive studies of trans-acting variation.

Conclusions:

• A detailed map of human cis-acting regulatory variation is proposed as a future goal.
• Limitations include the availability of diverse tissue panels from large individual cohorts.
• Comprehensive studies of trans-acting variation present significant knowledge gaps and feasibility challenges.