Haplotype inference in random population samples

Am J Hum Genet. 2002 Nov;71(5):1129-37. doi: 10.1086/344347. Epub 2002 Oct 17.


Contemporary genotyping and sequencing methods do not provide information on linkage phase in diploid organisms. The application of statistical methods to infer and reconstruct linkage phase in samples of diploid sequences is a potentially time- and labor-saving method. The Stephens-Smith-Donnelly (SSD) algorithm is one such method, which incorporates concepts from population genetics theory in a Markov chain-Monte Carlo technique. We applied a modified SSD method, as well as the expectation-maximization and partition-ligation algorithms, to sequence data from eight loci spanning >1 Mb on the human X chromosome. We demonstrate that the accuracy of the modified SSD method is better than that of the other algorithms and is superior in terms of the number of sites that may be processed. Also, we find phase reconstructions by the modified SSD method to be highly accurate over regions with high linkage disequilibrium (LD). If only polymorphisms with a minor allele frequency >0.2 are analyzed and scored according to the fraction of neighbor relations correctly called, reconstructions are 95.2% accurate over entire 100-kb stretches and are 98.6% accurate within blocks of high LD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms*
  • Chromosomes, Human, X
  • Haplotypes*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Software*