A global reference for human genetic variation

A global reference for human genetic variation · SciRah

^aDepartment of Genetics, Albert Einstein College of Medicine, Bronx, 10461, New York, USA
^bCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USA
^cVertex Pharmaceuticals, Boston, 02210, Massachusetts, USA
^dWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK
^eIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Nr Saffron Walden, CB10 1XL, Essex, UK
^fMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA
^gCenter for Comparative and Population Genomics, Cornell University, Ithaca, 14850, New York, USA
^hDepartment of Statistics, University of Oxford, Oxford, OX1 3TG, UK
ⁱWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
^jDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, 98195, Washington, USA
^kHoward Hughes Medical Institute, University of Washington, Seattle, 98195, Washington, USA
^lEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
^mThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USA
ⁿBaylor College of Medicine, Human Genome Sequencing Center, Houston, 77030, Texas, USA
^oUS National Institutes of Health, National Human Genome Research Institute, 31 Center Drive, Bethesda, 20892, Maryland, USA
^pCentre of Genomics and Policy, McGill University, Montreal, H3A 1A4, Quebec, Canada
^qEuropean Molecular Biology Laboratory, Genome Biology Research Unit, Meyerhofstr. 1, Heidelberg, Germany
^rDepartment of Life Sciences, Ewha Womans University, Ewhayeodae-gil, Seodaemun-gu, Seoul, South Korea, 120-750
^sThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, 06032, Connecticut, USA
^tMax Planck Institute for Molecular Genetics, D-14195 Berlin-Dahlem, Germany
^uDahlem Centre for Genome Research and Medical Systems Biology, D-14195 Berlin-Dahlem, Germany
^vMcDonnell Genome Institute at Washington University, Washington University School of Medicine, St Louis, 63108, Missouri, USA
^wUSTAR Center for Genetic Discovery & Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, 84112, Utah, USA
^xAffymetrix, Santa Clara, California, 95051, USA
^yUS National Institutes of Health, National Center for Biotechnology Information, 45 Center Drive, Bethesda, 20892, Maryland, USA
^zBGI-Shenzhen, Shenzhen 518083, China
^aaDepartment of Biology, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, 2200, Denmark
^abDepartment of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, 21 Sassoon Road, Hong Kong
^acMacau University of Science and Technology, Avenida Wai long, Taipa, 999078, Macau, China
^adPrincess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 80205, Saudi Arabia
✉Corresponding author

Abstract

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics. The 1000 Genomes Project has sought to comprehensively catalogue human genetic variation across populations, providing a valuable public genomic resource. The data obtained so far have found applications ranging from association studies and fine mapping studies to the filtering of likely neutral variants in rare-disease cohorts. The authors now report on the final phase of the project, phase 3, which covers previously uncharacterized areas of human genetic diversity in terms of the populations sampled and categories of characterized variation. The sample now includes more than 2,500 individuals from 26 global populations, with low coverage whole-genome and deep exome sequencing, as well as dense microarray genotyping. They find that while most common variants are shared across populations, rarer variants are often restricted to closely related populations. The authors also demonstrate the use of the phase 3 dataset as a reference panel for imputation to improve the resolution in genetic association studies.

TL;DRThe 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping. (Semantic Scholar)

A global reference for human genetic variation

Abstract

Plain-language summary

Discussion