Location: HSEB Room 2948 Gene mapping methods identify genes and mutational variants that underlie heritable traits. The term, identity by descent (IBD), is used for describing genomic material in individual samples that is inherited from a common founder. It is a fundamental concept that has been applied in gene mapping techniques, such as linkage analysis and genome-wide association studies (GWAS). In this dissertation, we develop and apply multi-locus shared genomic segment (SGS) methods that utilizes identity-by-state (IBS) in unphased genotype data to infer regions of IBD. The methods of directing IBS mapping is computationally efficient for whole genome high-density single nucleotide polymorphism (SNP) data, and can be used to address situations where statistical methods for IBD calculation is cumbersome. We use SGS to address population genetic questions, and through its application we proposed regions of recent positive selection in human genome. Knowledge of evolutionary genetics and its localization in the human genome can shed light in gene mapping of common complex traits. In its applications for high-risk pedigrees, SGS has shown its potential for investigating rare risk variants in simulated data, as well as mapping of breast cancer disease loci in real genotype dataset. Our findings suggest that SGS methods have good potential for evolutionary genetic study and disease gene mapping. The design and analysis strategies demonstrated in this dissertation aim to provide additional tools for innovational studies for investigation of common complex diseases. The dissection of disease etiologies carried out in genetic epidemiology society are making contributions to translational studies of personalized genetic medicine, as well as transformation of public health policy.
July 29, 2011
10:00 am