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Originally published as Genetics Published Articles Ahead of Print on October 18, 2007.

Genetics, Vol. 177, 1929-1940, November 2007, Copyright © 2007
doi:10.1534/genetics.107.079525

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A New Method for Haplotype Inference Including Full-Sib Information

Xiang Dong Ding*,{dagger}, Henner Simianer* and Qin Zhang{dagger},1

* University of Goettingen, Institute of Animal Breeding and Genetics, 37075 Goettingen, Germany and {dagger} State Key Laboratories of Agrobiotechnology, Key Laboratory for Animal Breeding and Genetics of Ministry of Agriculture of China, College of Animal Science and Technology, China Agricultural University, Beijing, 100094, China

1 Corresponding author: College of Animal Science and Technology, China Agricultural University, Beijing, 100094, China.
E-mail: qzhang{at}cau.edu.cn

Recent literature has suggested that haplotype inference through close relatives, especially from nuclear families, can be an alternative strategy in determining linkage phase and estimating haplotype frequencies. In the case of no possibility to obtain genotypes for parents, and only full-sib information being used, a new approach is suggested to infer phase and to reconstruct haplotypes. We present a maximum-likelihood method via an expectation-maximization algorithm, called FSHAP, using only full-sib information when parent information is not available. FSHAP can deal with families with an arbitrary number of children, and missing parents or missing genotypes can be handled as well. In a simulation study we compare FSHAP with another existing expectation-maximization (EM)-based approach (FAMHAP), the conditioning approach implemented in FBAT and GENEHUNTER, which is only pedigree based and assumes linkage equilibrium. In most situations, FSHAP has the smallest discrepancy of haplotype frequency estimation and the lowest error rate in haplotype reconstruction, only in some cases FAMHAP yields comparable results. GENEHUNTER produces the largest discrepancy, and FBAT produces the highest error rate in offspring in most situations. Among the methods compared, FSHAP has the highest accuracy in reconstructing the diplotypes of the unavailable parents. Potential limitations of the method, e.g., in analyzing very large haplotypes, are indicated and possible solutions are discussed.






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Copyright © 2007 by the Genetics Society of America.