Genetics and Genomics Commons^™

System Genetic Analysis Of Mechanisms Underlying Excessive Alcohol Consumption, Maren L. Smith

Theses and Dissertations

Increased alcohol consumption over time is one of the characteristic symptoms of Alcohol Use Disorder (AUD). The molecular mechanisms underlying this escalation in intake is still the subject of study. However, the mesocortical and mesolimbic dopamine pathways, and the extended amygdala, because of their involvement in reward and reinforcement are believed to play key roles in these behavioral changes. Multiple gene expression studies have shown that alcohol affects the expression of thousands of genes in the brain. The studies discussed in this document use the systems biology technique of co-expression network analysis to attempt to find

patterns within genome-wide expression …

A Pipeline For Creation Of Genome-Scale Metabolic Reconstructions, Shaun W. Norris

Theses and Dissertations

The decreasing costs of next generation sequencing technologies and the increasing speeds at which they work have lead to an abundance of 'omic datasets. The need for tools and methods to analyze, annotate, and model these datasets to better understand biological systems is growing. Here we present a novel software pipeline to reconstruct the metabolic model of an organism in silico starting from its genome sequence and a novel compilation of biological databases to better serve the generation of metabolic models. We validate these methods using five Gardnerella vaginalis strains and compare the gene annotation results to NCBI and the …

Power Analysis In Applied Linear Regression For Cell Type-Specific Differential Expression Detection, Edmund Glass

Theses and Dissertations

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from any tissues suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. However, this variability may actually be advantageous, as heterogeneous gene expression measurements coupled with cell counts may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression. Yet, they do not consider many artifacts hidden in high-dimensional gene expression …

Genomic Comparisons And Genome Architecture Of Divergent Trypanosoma Species, Katie Bradwell

Theses and Dissertations

Virulent Trypanosoma cruzi, and the non-pathogenic Trypanosoma conorhini and Trypanosoma rangeli are protozoan parasites with divergent lifestyles. T. cruzi and T. rangeli are endemic to Latin America, whereas T. conorhini is tropicopolitan. Reduviid bug vectors spread these parasites to mammalian hosts, within which T. rangeli and T. conorhini replicate extracellularly, while T. cruzi has intracellular stages. Firstly, this work compares the genomes of these parasites to understand their differing phenotypes. Secondly, genome architecture of T. cruzi is examined to address the effect of a complex hybridization history, polycistronic transcription, and genome plasticity on this organism, and study its highly …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …