Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel.

Published

Journal Article

A major use of the 1000 Genomes Project (1000 GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000 GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants.

Full Text

Duke Authors

Cited Authors

  • Delaneau, O; Marchini, J; 1000 Genomes Project Consortium,

Published Date

  • June 13, 2014

Published In

Volume / Issue

  • 5 /

Start / End Page

  • 3934 -

PubMed ID

  • 25653097

Pubmed Central ID

  • 25653097

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms4934

Language

  • eng