Detection of Sharing by Descent, Long-range Phasing and Haplotype Imputation

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Jan 24

PMID 19165921

Citations 275

Authors

Augustine Kong

Gisli Masson

Michael L Frigge

Arnaldur Gylfason

Pasha Zusmanovich

Gudmar Thorleifsson

Pall I Olason

Andres Ingason

Stacy Steinberg

Thorunn Rafnar

Patrick Sulem

Magali Mouy

Frosti Jonsson

Unnur Thorsteinsdottir

Daniel F Gudbjartsson

Hreinn Stefansson

Kari Stefansson

Affiliations

Soon will be listed here.

Abstract

Uncertainty about the phase of strings of SNPs creates complications in genetic analysis, although methods have been developed for phasing population-based samples. However, these methods can only phase a small number of SNPs effectively and become unreliable when applied to SNPs spanning many linkage disequilibrium (LD) blocks. Here we show how to phase more than 1,000 SNPs simultaneously for a large fraction of the 35,528 Icelanders genotyped by Illumina chips. Moreover, haplotypes that are identical by descent (IBD) between close and distant relatives, for example, those separated by ten meioses or more, can often be reliably detected. This method is particularly powerful in studies of the inheritance of recurrent mutations and fine-scale recombinations in large sample sets. A further extension of the method allows us to impute long haplotypes for individuals who are not genotyped.

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