Haplotype Blocks.ppt

Haplotype Blocks An Overview A. Polanski Department of Statistics Rice University Key Papers N. Patil et al., (2001), Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21, Science, vol. 294, pp. 1719-1723 N. Wang et al., (2002), Distribution of Recombination Crossovers and the Origin of Haplotype Blocks: The Interplay of Population History, Recombination and Mutation, Am. J. Hum. Genet., vol. 71, pp. 1227-1234. K. Zhang et al., (2002), A Dynamic Programming Algorithm for Haplotype Block Partitioning, PNAS, vol. 99, pp. 7335-7339 Supplementary Papers R. Hudson, N. Kaplan, (1985), Statistical Properties of the Number of Recombination Events in The History of a Sample of DNA sequences, Genetics, vol. 111, pp. 147-164 R. Hudson, 2002, Generating Samples under a Wright-Fisher Neutral Model of Genetic Variation, Bioinformatics, vol. 18, pp. 337-338 D. Reich et al., (2001), Linkage Disequilibrium in the Human Genome, Nature, vol. 411, pp. 199-204 What are Haplotype Blocks ? Haplotype block = a sequence of contiguous markers on DNA, homogeneous according to some criterion Markers = Single Nucleotide Polymorphisms (SNPs) Data (Patil et al. 2001) Chromosome 21 Physically separated the two copies of chromosome 21 using a rodent-human somatic cell hybrid technique Sample of 20 copies of chromosome 21 bases) Found: 35989 SNPs Problems How do we determine boundaries between blocks ? Average value of standarized coefficient of linkage disequilibrium is greater than some threshold (Wang et al. 2002, Reich et al. 2001) Infer sites in the sample of DNA sequences where recombination events happened in the past history (Wang et al. 2002, Hudson, 2002) Chromosome coverage – minimum number of SNPs to account for majority of haplotypes (Patil et al. 2001, Zhang et al. 2002) What evolutionary forces are responsible for haplotype blocks formation ? Mutation Genetic drift Recombination Recombination h