title: Haplotype block partitioning and tag SNP selection using genotype data and their applications to association studies.
abstract: Recent studies have revealed that linkage disequilibrium (LD) patterns vary across the human genome with some regions of high LD interspersed by regions of low LD. A small fraction of SNPs (tag SNPs) is sufficient to capture most of the haplotype structure of the human genome. In this paper, we develop a method to partition haplotypes into blocks and to identify tag SNPs based on genotype data by combining a dynamic programming algorithm for haplotype block partitioning and tag SNP selection based on haplotype data with a variation of the expectation maximization (EM) algorithm for haplotype inference. We assess the effects of using either haplotype or genotype data in haplotype block identification and tag SNP selection as a function of several factors, including sample size, density or number of SNPs studied, allele frequencies, fraction of missing data, and genotyping error rate, using extensive simulations. We find that a modest number of haplotype or genotype samples will result in consistent block partitions and tag SNP selection. The power of association studies based on tag SNPs using genotype data is similar to that using haplotype data.
authors.affiliation: Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-1113, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: Zhaohui S
authors.initials: ZS
authors.lastname: Qin
authors.forename: Jun S
authors.initials: JS
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Waterman
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
mesh_terms: D000465:Algorithms; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods / Q000706:statistics & numerical data; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003198:Computer Simulation; D015342:DNA Probes / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D012107:Research Design / Q000706:statistics & numerical data; D018401:Sample Size
chemical_list: D015342:DNA Probes; D005819:Genetic Markers