Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - The effect of haplotype-block definitions on inference of haplotype-block structure and htSNPs selection
AU - Ding, Keyue
AU - Zhou, Kaixin
AU - Zhang, Jing
AU - Knight, Joanne
AU - Zhang, Xuegong
AU - Shen, Yan
PY - 2005/1
Y1 - 2005/1
N2 - It has been recently suggested that the human genome is organized as a series of haplotype blocks, and efforts to create a genome-wide haplotype map are already underway. Several computational algorithms have been proposed to partition the genome. However, little is known about their behaviors in relation to the haplotype-block partitioning and haplotype-tagging SNPs selection. Here, we present a systematic comparison of three classes of haplotype-block partition definitions, a diversity-based method, a linkage-disequilibrium (LD)-based method, and a recombination-based method. The data used were derived from a coalescent simulation under both a uniform recombination model and one that assumes recombination hotspots. There were considerable differences in haplotype information loss in the measure of entropy when the partition methods were compared under different population-genetics scenarios. Under both recombination models, the results from the LD-based definition and the recombination-based definition were more similar to each other than were the results from the diversity-based definition. This work demonstrates that when undertaking haplotype-based association mapping, the choice of haplotype-block definition and SNP selection requires careful consideration.
AB - It has been recently suggested that the human genome is organized as a series of haplotype blocks, and efforts to create a genome-wide haplotype map are already underway. Several computational algorithms have been proposed to partition the genome. However, little is known about their behaviors in relation to the haplotype-block partitioning and haplotype-tagging SNPs selection. Here, we present a systematic comparison of three classes of haplotype-block partition definitions, a diversity-based method, a linkage-disequilibrium (LD)-based method, and a recombination-based method. The data used were derived from a coalescent simulation under both a uniform recombination model and one that assumes recombination hotspots. There were considerable differences in haplotype information loss in the measure of entropy when the partition methods were compared under different population-genetics scenarios. Under both recombination models, the results from the LD-based definition and the recombination-based definition were more similar to each other than were the results from the diversity-based definition. This work demonstrates that when undertaking haplotype-based association mapping, the choice of haplotype-block definition and SNP selection requires careful consideration.
KW - Algorithms
KW - Chromosome Mapping
KW - Computational Biology
KW - Computer Simulation
KW - Genetic Markers
KW - Genetic Variation
KW - Genetics, Population
KW - Genome, Human
KW - Humans
KW - Models, Genetic
KW - Polymorphism, Single Nucleotide
KW - Recombination, Genetic
KW - Selection, Genetic
U2 - 10.1093/molbev/msh266
DO - 10.1093/molbev/msh266
M3 - Journal article
C2 - 15371531
VL - 22
SP - 148
EP - 159
JO - Molecular Biology and Evolution
JF - Molecular Biology and Evolution
SN - 0737-4038
IS - 1
ER -