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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A.K. and K.S. planned and supervised the research. A.K. wrote the first draft of the paper and together with K.S. and G.M. did most of the writing for the final version. The idea of long range phasing (LRP) originated from A.K. and G.M., motivated by a problem posed by H.S. G.M. and P.I.O. coded the LRP algorithm. A.K., M.L.F., A.G. and P.Z. contributed to the study of the population characteristics of Iceland. A.K., G.T. and M.L.F. contributed to the recombination study. A.K., H.S., S.S. and A.I. contributed to the study of the deletion at 15q11. A.K., D.F.G., T.R., P.S. and M.L.F. contributed to the haplotype imputation study. U.T., M.M. and F.J. contributed to genotyping.
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Kong, A., Masson, G., Frigge, M. et al. Detection of sharing by descent, long-range phasing and haplotype imputation. Nat Genet 40, 1068–1075 (2008). https://doi.org/10.1038/ng.216
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DOI: https://doi.org/10.1038/ng.216
