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Global haplotype partitioning for maximal associated SNP pairs

DOI: 10.1186/1471-2105-10-269

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Abstract:

In comparison with other methods, our algorithm reports blocks of larger average size. Nevertheless, the haplotype diversity within the blocks is captured by a small number of tagSNPs. Resampling HapMap haplotypes under a block-based model of recombination showed that our algorithm is robust in reproducing the same partitioning for recombinant samples. Our algorithm performed better than previously reported models in a case-control association study aimed at mapping a single locus trait, based on simulation results that were evaluated by a block-based statistical test. Compared to methods of haplotype block partitioning, we performed best on detection of recombination hotspots.Our proposed method divides chromosomes into the regions within which allelic associations of SNP pairs are maximized. This approach presents a native design for dimension reduction in genome-wide association studies. Our results show that the pairwise allelic association of SNPs can describe various features of genomic variation, in particular recombination hotspots.Analysis of Single Nucleotide Polymorphisms (SNPs) in the DNA of unrelated individuals revealed a block-like structure of haplotype variation along the human genome. Using the first available genome-wide data of SNPs on chromosome 21, Patil et al. [1] showed that in particular regions on the chromosome, the observed diversity of SNP haplotypes is less than the expected. Almost at the same time, a similar structure in haplotypes within a region of 103 SNPs on chromosome region 5q31 was reported by Daly et al. [2]. In the latter study, a block structure of haplotypes was revealed using a Hidden Markov Model for estimating recombination rates. This approach, unlike models based on haplotype diversity, incorporated a quantity measuring Linkage Disequilibrium (LD) between pairs of SNPs.It is well known that effects such as population bottlenecks, geographic isolation, and natural selection can increase the extent of linkage disequilibr

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