Detection of sharing by descent, long-range phasing and haplotype imputation

• Published in: Nature genetics Vol. 40; no. 9; pp. 1068 - 1075
• Main Authors: Kong, Augustine, Stefansson, Kari, Masson, Gisli, Frigge, Michael L, Gylfason, Arnaldur, Zusmanovich, Pasha, Thorleifsson, Gudmar, Olason, Pall I, Ingason, Andres, Steinberg, Stacy, Rafnar, Thorunn, Sulem, Patrick, Mouy, Magali, Jonsson, Frosti, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F, Stefansson, Hreinn
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2008; Nature Publishing Group
• Subjects: Agriculture; Algorithms; Analysis; Animal Genetics and Genomics; Base Sequence; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; DNA microarrays; Families & family life; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Function; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Genetics, Population; Genotype & phenotype; Haplotypes; Human Genetics; Humans; Iceland; Inheritance Patterns; Major Histocompatibility Complex; Male; Models, Genetic; Multiple imputation (Statistics); Parents & parenting; Polymorphism, Single Nucleotide; Single nucleotide polymorphisms; Statistical methods; Studies; Surrogate mothers; Iceland; Detection; Haplotype
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.216

Augustine Kong and colleagues describe an approach for phasing SNPs into long haplotypes spanning multiple blocks of linkage disequilibrium. The method, termed long-range phasing, can be also used to impute long haplotypes for ungenotyped individuals. 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.