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