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.

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2)1. We used 'longrange haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection2, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population: LARGE and DMD, both related to infection by the Lassa virus3, in West Africa; SLC24A5 and SLC45A2, both involved in skin pigmentation4,5, in Europe; and EDAR and EDA2R, both involved in development of hair follicles6, in Asia. ©2007 Nature Publishing GroupCorrespondence and requests for materials should be addressed to P.C.S. (pardis@broad.mit.edu).. * These authors contributed equally to this work. † Lists of participants and affiliations appear at the end of the paper. Author Contributions P.C.S., P.V., B.F. and E.S.L. initiated the project. P.V., B.F. and P.C.S. developed key software. P.C.S., P.V., B.F., S.F.S., J.L., E.H., C.C., X.X., E.B., S.A.McC. and R.G. performed analysis. P.C.S., E.B. and E.H. performed experiments. P.C.S., E.S.L., P.V. and S.F.S. wrote the manuscript.Full Methods and any associated references are available in the online version of the paper at www.nature.com/nature.Supplementary Information is linked to the online version of the paper at www.nature.com/nature.Reprints and permissions information is available at www.nature.com/reprints. An increasing amount of information about genetic variation, together with new analytical methods, is making it possible to explore the recent evolutionary history of the human population. The first phase of the International Haplotype Map, including ~1 million single nucleotide polymorphisms (SNPs)7, allowed preliminary examination of natural selection in humans. Now, with the publication of the Phase 2 map (HapMap2)1 in a companion paper, over 3 million SNPs have been genotyped in 420 chromosomes from three continents (120 European (CEU), 120 African (YRI) and 180 Asian from Japan and China (JPT + CHB)). Europe PMC Funders GroupIn our analysis of HapMap2, we first implemented two widely used tests that detect recent positive selection by finding common alleles carried on unusually long haplotypes2. The two, the Long-Range Haplotype (LRH)8 and the integrated Haplotype Score (iHS)9 tests...

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A haplotype map of the human genomeThe International HapMap Consortium* Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

International audienceThe use of genetics and genomics within a wide range of health care settings requires health professionals to develop expertise in order to practise appropriately. There is a need for a common minimum standard of competence in genetics for health professionals in Europe but due to differences in professional education and regulation between European countries, setting curricula may not be practical. Core competences are used as a basis for health professional education in many fields and settings. An Expert Group working under the auspices of the EuroGentest project and European Society of Human Genetics Education Committee agreed that a pragmatic solution to the need to establish common standards for education and practice in genetic healthcare was to agree a set of core competences that could apply across Europe. These were agreed through an exhaustive process of consultation with relevant health professionals and patient groups. Sets of competences for practitioners working in primary, secondary and tertiary care have been agreed and were approved by the European Society of Human Genetics. The competences provide an appropriate framework for genetics education of health professionals across national boundaries and the suggested learning outcomes are available to guide development of curricula that are appropriate to the national context, educational system and healthcare setting of the professional involved. Collaboration between individuals from many European countries and professions has resulted in an adaptable framework for both pre-registration and continuing professional education. This competence framework has the potential to improve the quality of genetic healthcare for patients globally

The multicriteria decision analysis approach piloted works and could be developed for use by payers and health technology assessment bodies.

Commercial promotion of unsupported therapeutic uses of stem cells is a global problem that should be addressed by coordinated approaches at the national and international levels.