Gene expression variability within and between human populations and implications toward disease susceptibility

Area of Science:

• Genomics
• Human Genetics
• Molecular Biology

Background:

• Gene expression variation contributes to phenotypic diversity.
• Understanding within- and between-population gene expression variability is crucial but remains challenging.

Purpose of the Study:

• To investigate the dynamic range of gene expression variability across individuals within human populations.
• To explore the relationship between gene expression variability, sequence polymorphism, and differential gene expression.

Main Methods:

• Analyzed expression variability of approximately 18,000 human genes across HapMap populations.
• Associated expression variability with sequence polymorphism, focusing on SNPs in untranslated regions (UTRs).
• Performed genome-wide differential expression analysis.

Main Results:

• Most genes exhibit similar expression variability across populations; a small fraction shows significantly higher variability in specific populations.
• SNPs in untranslated regions of highly variable genes show elevated population heterozygosity.
• Many genes display reduced expression variability, limiting their potential for differential expression between populations.

Conclusions:

• Gene expression variability, particularly in specific genes, may explain differential susceptibility to infections such as HIV (Human Immunodeficiency Virus).
• Genes with high within-population variability are enriched in pathways related to HIV infection, including viral entry and replication.