title: Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA.
abstract: The efficiency of single-nucleotide polymorphism haplotype analysis may be increased by DNA pooling, which can dramatically reduce the number of genotyping assays. We develop a method for obtaining maximum likelihood estimates of haplotype frequencies for different pool sizes, assess the accuracy of these estimates, and show that pooling DNA samples is efficient in estimating haplotype frequencies. Although pooling K individuals increases ambiguities, at least for small pool size K and small numbers of loci, the uncertainty of estimation increases <K times that of unpooled DNA. We also develop the asymptotic variance-covariance of maximum likelihood estimates and evaluate the accuracy of variance estimates by Monte Carlo methods. When the sample size of pools is moderately large, the asymptotic variance estimates are rather accurate. Completely or partially missing genotyping information is allowed for in our analysis. Finally, our methods are applied to single-nucleotide polymorphisms in the angiotensinogen gene.
authors.affiliation: Laboratory of Statistical Genetics, The Rockefeller University, New York, NY 10021, USA. yyang@linkage.rockefeller.edu
authors.forename: Yaning
authors.initials: Y
authors.lastname: Yang
authors.forename: Jingshan
authors.initials: J
authors.lastname: Zhang
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
mesh_terms: D000465:Algorithms; D000704:Analysis of Variance; D000808:Angiotensinogen / Q000235:genetics; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D000808:Angiotensinogen; D004247:DNA