Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture

Area of Science:

• Genomics
• Population Genetics
• Transcriptomics

Background:

• Human genome sequencing reveals extensive genetic variation.
• Understanding the global distribution and functional impact of this variation remains incomplete.
• Transcriptome differences across diverse human populations are not systematically analyzed.

Purpose of the Study:

• Analyze gene expression variation, alternative splicing, and regulatory genetics across diverse human populations.
• Investigate the population genetics of regulatory variation.
• Characterize transcriptome differences across human migration history.

Main Methods:

• Sequenced genomes, exomes, and transcriptomes of lymphoblastoid cell lines from 45 individuals in the Human Genome Diversity Panel (HGDP).
• Populations sampled represent broad geographic human migration history.
• Utilized allelic expression analyses and compared with International Haplotype Map Phase 3 data.

Main Results:

• Approximately 25% of individual gene expression variation is attributable to population differences.
• Most population-specific variation (75.5%) arises from expression, not splicing, with few genes showing differential splicing.
• Common regulatory variants have similar cellular effects across diverse populations.

Conclusions:

• Gene expression variation is significantly influenced by population background.
• Cellular effects of common regulatory variants are largely conserved across diverse human populations.
• Provides a resource for studying functional genetic differences across human populations.