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Genotype, haplotype and copy-number variation in worldwide human populations

2008; Nature Portfolio; Volume: 451; Issue: 7181 Linguagem: Inglês

10.1038/nature06742

1476-4687

Mattias Jakobsson, Sonja W. Scholz, Paul Scheet, J. Raphael Gibbs, Jenna M. VanLiere, Hon‐Chung Fung, Zachary A. Szpiech, J. H. Degnan, Kai Wang, Rita Guerreiro, José Brás, Jennifer C. Schymick, Dena Hernández, Bryan J. Traynor, Javier Simón‐Sánchez, Mar Matarín, Angela Britton, Joyce van de Leemput, Ian Rafferty, Maja Bućan, Howard M. Cann, John Hardy, Noah A. Rosenberg, Andrew Singleton,

Genomics and Rare Diseases

The analysis of genome-wide patterns of variation in human populations can provide genetic evidence of patterns of human migration and adaptation across the world. Two contrasting papers in this issue illustrate the power of the method. By combining a large number of datasets, Lohmueller et al. obtain precise estimates of the number of deleterious mutations carried by each of 15 African-Americans and 20 European-Americans, resequenced across 11,000 genes. They find that individuals with a European background have more potentially damaging mutations lurking in their genomes than those with an African background. This is interpreted as a genetic legacy from the 'out-of-Africa' bottleneck that accompanied the peopling of Europe. Jakobsson et al. take a broader snapshot of human variation by examining 29 populations in the Human Genome Diversity Project. They obtain genotype data for over 500,000 markers in the human genome. Echoing the study of Americans with African and European backgrounds, these data reveal increasing linkage disequilibrium with increasing geographic distance from Africa. A report detailing genotype data for over 500,000 markers in the human genome by examining 29 populations in the Human Genome Diversity Project. Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups1,2,3. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected—including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas—the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.