Physical Sciences and Mathematics Commons^™

Association Of Structural Variation (Sv) With Cardiometabolic Traits In Finns, Lei Chen

Arts & Sciences Electronic Theses and Dissertations

Cardiovascular diseases (CVDs) are known to be associated with a variety of quantitative risk factors such as cholesterol, metabolites, and insulin. Understanding the genetic basis of these quantitative traits can shed light on the etiology, prevention, diagnosis, and treatment of disease. However most prior trait-mapping studies have focused on single nucleotide variants (SNVs) and Indels, with the contribution of structural variation (SV) remaining unknown. In this thesis, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. In the first chapter, we used sensitive methods to identify and genotype 129,166 high-confidence …

The Phylogeography Of Rare Central Tennessee Glade Endemics Trifolium Calcaricum And Viola Egglestonii, Rachel Ann Lyman

Arts & Sciences Electronic Theses and Dissertations

Endemic species are range-restricted to a particular type of habitat and generally occur in a few small populations. Often endemic species are threatened or endangered due to their geographic isolation and limited habitat breadth. Despite the fact that understanding factors that may have shaped the evolutionary history of a species with a narrow distribution can provide important insights for their management and conservation, little is known about the historical forces that gave rise to many endemic species. Endemic species can arise because of factors such as variation in climate, geographic barriers, and habitat specificity, or the combination of several of …

Genetics Of Pediatric Musculoskeletal Disorders, Lilian Antunes

Arts & Sciences Electronic Theses and Dissertations

Pediatric musculoskeletal disorders are an extremely broad category of diseases that are often inherited. While individually rare, collectively these disorders are common, affecting around 3% of live births in the US. Despite the mounting clinical and molecular evidence for a genetic etiology, the cause for many patients with pediatric musculoskeletal disorders remain largely unknown. Major challenges in rare pediatric diseases include recruiting large numbers of patients and determining the significance and functional impacts of variants associated with disease within individuals or families. Whole exome sequencing (WES) is a powerful tool to identify coding variants that are associated with rare pediatric …

Multi-Omics Integration For Gene Fusion Discovery And Somatic Mutation Haplotyping In Cancer, Steven Mason Foltz

Arts & Sciences Electronic Theses and Dissertations

Cancer is a disease caused by changes to the genome and dysregulation of gene expression. Among many types of mutations, including point mutations, small insertions and deletions, large scale structural variants, and copy number changes, gene fusions are another category of genomic and transcriptomic alteration that can lead to cancer and which can serve as therapeutic targets. We studied gene fusion events using data from The Cancer Genome Atlas, including over 9,000 patients from 33 cancer types, finding patterns of gene fusion events and dysregulation of gene expression within and across cancer types. With data from the CoMMpass study (Multiple …

Grammar And Variation: Understanding How Cis-Regulatory Information Is Encoded In Mammalian Genomes, Dana Michele King

Arts & Sciences Electronic Theses and Dissertations

Understanding how genotype leads to phenotype is key to understand both the development and dysfunction of complex organisms. In the context of regulating the gene expression patterns that contribute to cell identity and function, the goal of my thesis research is to how changes in genome sequence may impact impact gene expression by determining how sequence features contribute to regulatory potential. To accomplish this goal, I first leveraged the key regulatory role of pluripotency transcription factors (TFs) in mouse embryonic stem cells (mESCs) and tested synthetically generated and genomic identified combinations of binding site for four TFs, OCT4, SOX2, KLF4, …

Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough

Arts & Sciences Electronic Theses and Dissertations

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants …

Genetic Imputation: Accuracy To Application, Shelina Raynell Ramnarine

Arts & Sciences Electronic Theses and Dissertations

Genotype imputation, the process of inferring genotypes for untyped variants, is used to identify and refine genetic association findings. This body of work focuses on assessing imputation accuracy and uses imputed data to identify genetic contributors to mentholated cigarette preference.

Inaccuracies in imputed data can distort the observed association between variants and a disease. Many statistics are used to assess accuracy; some compare imputed to genotyped data and others are calculated without reference to true genotypes. Prior work has shown that the Imputation Quality Score (IQS), which is based on Cohens kappa statistic and compares imputed genotype probabilities to true …