Architecture of population-differentiated polymorphisms in the human genome

Autoři: Maulana Bachtiar aff001;  Yu Jin aff002;  Jingbo Wang aff001;  Tin Wee Tan aff001;  Samuel S. Chong aff004;  Kenneth H. K. Ban aff001;  Caroline G. L. Lee aff001
Působiště autorů: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore aff001;  Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore aff002;  National Supercomputing Centre Singapore, Singapore aff003;  Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore aff004;  Cancer & Stem Cell Biology Programme, Duke-NUS Graduate Medical School, Singapore aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224089


Population variation in disease and other phenotype are partly attributed to single nucleotide polymorphisms (SNPs) in the human genome. Due to selection pressure, two individuals from the same ancestral population have more genetic similarity compared to individuals from further geographic regions. Here, we elucidated the genomic population differentiation pattern, by interrogating >22,000,000 SNPs. Majority of population-differentiated (pd) SNPs (~95%), including the potentially functional (pf) (~84%) subset reside in non-genic regions, compared to the proportion of all SNPs (58%) found in non-genic regions. This suggests that differences between populations are more likely due to differences in gene regulation rather than protein function. Actin Cytoskeleton, Axonal Guidance and Protein Kinase A signaling pathways are enriched with genes carrying at least three pdSNPs (enriched pdGenes), while Antigen Presentation, Hepatic Fibrosis and Huntington Disease Signalling pathways are over-represented by enriched pf-pdGenes. An inverse correlation between chromosome size and the proportion of pd-/pf-pdSNPs was observed. Smaller chromosomes have relatively more of such SNPs including genes carrying these SNPs. Genes associated with common diseases and enriched with these pd-/pfpdSNPs are localized to 11 different chromosomes, with immune-related disease pd/pf-pdGenes mainly residing in chromosome 6 while neurological disease pd/pf-pdGenes residing in smaller chromosomes including chromosome 21/22. The associated diseases were reported to show population differences in incidence, severity and/or etiology. In summary, this study highlights the non-sporadic nature of population differentiation footprint in the human genome, which can potentially lead to the identification of genomic regions that play roles in the manifestation of phenotypic differences, including in disease predisposition and drug response.

Klíčová slova:

Comparative genomics – Europe – Gene regulation – Chromosome structure and function – Chromosomes – Population genetics – Structural genomics – Human genomics


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2019 Číslo 10