Statistical methods for multi-marker testing in genetic association studies

As the development of genotyping and next-generation sequencing technologies, multi-marker testing in genome-wide association study and rare variant association study became active research areas in statistical genetics. This dissertation contains three methodologies for association study by exploring different genetic data features and demonstrates how to use those methods to test genetic association hypothesis. The methods can be categorized into in three scenarios: 1) multi-marker testing for strong Linkage Disequilibrium regions, 2) multi-marker testing for family-based association studies, 3) multi-marker testing for rare variant association study. I also discussed the advantage of using these methods and demonstrated its power by simulation studies and applications to real genetic data.

ASSESSMENT OF ASPEN AND NORTHERN HARDWOODS EXTENT IN THIRTY THREE COUNTIES OF UPPER/LOWER MICHIGAN

The importance of the United States' wood and wood byproducts as biomass feedstocks is increasing as the concern about security and sustainability of global energy production continues to rise. Thus, second generation woody feedstock sources in Michigan, e.g., hybrid poplar and hybrid willow (Populus spp.), are viewed as a potential source of biomass for the proposed biofuel ethanol production plant in Kinross, MI. It is important to gain an understanding of the spatial distribution of current feedstock sources, harvesting accessibility via the transportation infrastructure and land ownerships in order to ensure long-term feedstock extent. This research provides insights into the current extent of aspen and northern hardwoods, and an assessment of potential for expanding the area of these feedstock sources based on pre-European settlement conditions. A geographic information system (GIS) was developed to compile available geospatial data for 33 counties located within 150 miles of the Kinross facility. These include present day and pre-European settlement land use/cover, soils, road infrastructure, and land ownerships. The results suggest that a significant amount of northern hardwoods has been converted to other land use/cover types since European settlement, and the "scattering" of aspen stands has increased. Furthermore, a significant amount of woody biomass is available in close proximity to the existing road network, which can be effectively utilized as feedstock. Potential aspen and northern hardwoods restoration areas are identified in the vicinity of road networks which can be used for future woody feedstock production.

POPLAR GENE EXPRESSION DATA ANALYSIS PIPELINES

Analyzing large-scale gene expression data is a labor-intensive and time-consuming process. To make data analysis easier, we developed a set of pipelines for rapid processing and analysis poplar gene expression data for knowledge discovery. Of all pipelines developed, differentially expressed genes (DEGs) pipeline is the one designed to identify biologically important genes that are differentially expressed in one of multiple time points for conditions. Pathway analysis pipeline was designed to identify the differentially expression metabolic pathways. Protein domain enrichment pipeline can identify the enriched protein domains present in the DEGs. Finally, Gene Ontology (GO) enrichment analysis pipeline was developed to identify the enriched GO terms in the DEGs. Our pipeline tools can analyze both microarray gene data and high-throughput gene data. These two types of data are obtained by two different technologies. A microarray technology is to measure gene expression levels via microarray chips, a collection of microscopic DNA spots attached to a solid (glass) surface, whereas high throughput sequencing, also called as the next-generation sequencing, is a new technology to measure gene expression levels by directly sequencing mRNAs, and obtaining each mRNA’s copy numbers in cells or tissues. We also developed a web portal (http://sys.bio.mtu.edu/) to make all pipelines available to public to facilitate users to analyze their gene expression data. In addition to the analyses mentioned above, it can also perform GO hierarchy analysis, i.e. construct GO trees using a list of GO terms as an input.