Gene expression variability within and between human populations and implications toward disease susceptibility.
Variations in gene expression level might lead to phenotypic diversity across individuals or populations. Although many human genes are found to have differential mRNA levels between populations, the extent of gene expression that could vary within and between populations largely remains elusive. To investigate the dynamic range of gene expression, we analyzed the expression variability of ∼18, 000 human genes across individuals within HapMap populations. Although ∼20% of human genes show differentiated mRNA levels between populations, our results show that expression variability of most human genes in one population is not significantly deviant from another population, except for a small fraction that do show substantially higher expression variability in a particular population. By associating expression variability with sequence polymorphism, intriguingly, we found SNPs in the untranslated regions (5' and 3'UTRs) of these variable genes show consistently elevated population heterozygosity. We performed differential expression analysis on a genome-wide scale, and found substantially reduced expression variability for a large number of genes, prohibiting them from being differentially expressed between populations. Functional analysis revealed that genes with the greatest within-population expression variability are significantly enriched for chemokine signaling in HIV-1 infection, and for HIV-interacting proteins that control viral entry, replication, and propagation. This observation combined with the finding that known human HIV host factors show substantially elevated expression variability, collectively suggest that gene expression variability might explain differential HIV susceptibility across individuals.
Li
Jingjing
J
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
Liu
Yu
Y
Kim
Taehyung
T
Min
Renqiang
R
Zhang
Zhaolei
Z
D018925:Chemokines / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011153:Population / Q000235:genetics; D020506:Untranslated Regions / Q000235:genetics; D053586:Virus Internalization; D014779:Virus Replication / Q000235:genetics
D018925:Chemokines; D020506:Untranslated Regions