14.4. Y chromosome HaplogroupsA maximum likelihood haplogroup tree under a HKY model of evolution was produced using phyML, and bootstrap values were produced using 100 subsamplings. Trees were produced using both all 2870 filtered sites (Supplementary Figure 7), and the 1971 UYR sites; though there was very little difference between the two trees. The haplogroup tree classifies all the major haplogroups as monomorphic, and recovers the relationships between them, with high bootstrap confidence. It also shows evidence for a deep division between haplogroups DE and CT, previously identified only by a single marker (P143; Karafet, Mendez et al. 2008). New insights into recent human evolution can also be gained from the branch lengths; for example, the short internal branch lengths within the haplogroup R1b relative to the other haplogroups suggest a recent expansion of this European haplogroup (Balaresque, Bowden et al. 2010).
Nature 467 , 1061–1073 (28 October 2010) doi:10.1038/nature09534
A map of human genome variation from population-scale sequencing
The 1000 Genomes Project Consortium
The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother–father–child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.