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Hum Mol Genet. 2010 Oct 15;19(R2):R221-6. doi: 10.1093/hmg/ddq403. Epub 2010 Sep 28.

Fine-scale population structure and the era of next-generation sequencing.

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  • 1Department of Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.

Abstract

Fine-scale population structure characterizes most continents and is especially pronounced in non-cosmopolitan populations. Roughly half of the world's population remains non-cosmopolitan and even populations within cities often assort along ethnic and linguistic categories. Barriers to random mating can be ecologically extreme, such as the Sahara Desert, or cultural, such as the Indian caste system. In either case, subpopulations accumulate genetic differences if the barrier is maintained over multiple generations. Genome-wide polymorphism data, initially with only a few hundred autosomal microsatellites, have clearly established differences in allele frequency not only among continental regions, but also within continents and within countries. We review recent evidence from the analysis of genome-wide polymorphism data for genetic boundaries delineating human population structure and the main demographic and genomic processes shaping variation, and discuss the implications of population structure for the distribution and discovery of disease-causing genetic variants, in the light of the imminent availability of sequencing data for a multitude of diverse human genomes.

PMID:
20876616
[PubMed - indexed for MEDLINE]
PMCID:
PMC2953744
Free PMC Article

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