A map of human genome variation from population-scale sequencing. Academic Article uri icon

Overview

MeSH

  • Calibration
  • Chromosomes, Human, Y
  • Computational Biology
  • DNA Mutational Analysis
  • DNA, Mitochondrial
  • Evolution, Molecular
  • Female
  • Genetic Association Studies
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Mutation
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • Recombination, Genetic
  • Sample Size
  • Selection, Genetic
  • Sequence Alignment

MeSH Major

  • Genetic Variation
  • Genetics, Population
  • Genome, Human
  • Genomics
  • Sequence Analysis, DNA

abstract

  • 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.

authors

publication date

  • October 28, 2010

has subject area

  • Calibration
  • Chromosomes, Human, Y
  • Computational Biology
  • DNA Mutational Analysis
  • DNA, Mitochondrial
  • Evolution, Molecular
  • Female
  • Genetic Association Studies
  • Genetic Variation
  • Genetics, Population
  • Genome, Human
  • Genome-Wide Association Study
  • Genomics
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Mutation
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • Recombination, Genetic
  • Sample Size
  • Selection, Genetic
  • Sequence Alignment
  • Sequence Analysis, DNA

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3042601

Digital Object Identifier (DOI)

  • 10.1038/nature09534

PubMed ID

  • 20981092

Additional Document Info

start page

  • 1061

end page

  • 1073

volume

  • 467

number

  • 7319