Haplotype block and genetic association

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dc.contributor.advisorGuerra, Rudyen_US
dc.creatorYu, Zhaoxiaen_US
dc.date.accessioned2009-06-04T07:59:46Zen_US
dc.date.available2009-06-04T07:59:46Zen_US
dc.date.issued2006en_US
dc.description.abstractThe recently identified (Daly et al. 2001 and Patil et al. 2001) block-like structure in the human genome has attracted much attention since each haplotype block contains limited sequence variation, which can reduce the complexity in genetic mapping studies. This dissertation focuses on estimating haplotype block structures and their application to genetic mapping using single nucleotide polymorphisms (SNPs) from unrelated individuals. Among other issues, the traditional single marker association study leads to the problem of multiple testing, which is still not well understood in the context of genomewide association studies. The haplotype-based approach is one way to lessen certain problems caused by multiple testing. There is also evidence that haplotype based tests have higher statistical power. We first propose a novel approach to estimate haplotype blocks based on pairwise linkage disequilibrium (LD). The application to simulated data shows that our new approach has higher power than several existing methods in identifying haplotype blocks. We also examine the impact of marker density and different tagging strategies on the estimation of haplotype blocks. We introduce a new statistic to measure the difference between two different block partitions. Applying the new statistic to real and simulated data we show that a higher marker density is needed than previously expected in order to recover the true block structure over a given region. Finally, we analyzed a real SNP data set. A comparison of the haplotype-SNP based method to the more traditional single-SNP based method shows that the two methods tend to agree more when halplotype block sizes are small. On the other hand, the haplotype-SNP based approach does not always have higher power than the single-SNP based study as is supported by theoretical considerations. Indeed, long haplotype blocks where the LD structure might be very complex can lead to inferior power compared to single-SNP approaches. In practice, it is recommended that single-SNP analyses be run routinely, especially in the presence of moderate to long blocks.en_US
dc.format.extent118 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS STAT. 2006 YUen_US
dc.identifier.citationYu, Zhaoxia. "Haplotype block and genetic association." (2006) Diss., Rice University. <a href="https://hdl.handle.net/1911/19001">https://hdl.handle.net/1911/19001</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/19001en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectBiostatisticsen_US
dc.subjectGeneticsen_US
dc.subjectStatisticsen_US
dc.titleHaplotype block and genetic associationen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentStatisticsen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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