Genetics Commons^™

The Foundations Of Network Dynamics In An Rna Recombinase System, Jessica Anne Mellor Yeates

Dissertations and Theses

How life originated from physical and chemical processes is one of the great questions still unanswered today. Studies towards this effort have transitioned from the notion of a single self-replicating entity to the idea that a network of interacting molecules made this initial biological leap. In order to understand the chemical kinetic and thermodynamic mechanisms that could engender pre-life type networks we present an empirical characterization of a network of RNA recombinase molecules. We begin with 1-, 2-, and 3-molecular ensembles and provide a game theoretic analysis to describe the frequency dependent dynamics of competing and cooperating RNA genotypes. This …

Identification Of Biomarkers For The Overall Survival Of Ovarian Cancer Patients, Kristi Mai

Graduate Theses and Dissertations

Rapid advance in sequencing technology has led to genome-wide analysis of genetic and epigenetic features simultaneously, making it possible to understand the biological mechanisms underlying cancer initiation and progression. However, how to identify important prognostic features poses a great challenge for both statistical modeling and computing. In this thesis, a network-based approach is applied to the Cancer Genome Atlas (TCGA) ovarian cancer data to identify important genes related to the overall survival of ovarian cancer patients. In the first step, a stepwise correlation-based selector is used to reduce the dimensionality of TCGA data, by filtering out a large number of …

Global Genetic Connectivity And Diversity In A Shark Of High Conservation Concern, The Oceanic Whitetip, Carcharhinus Longimanus, Cassandra L. Ruck

HCNSO Student Theses and Dissertations

The oceanic whitetip shark, Carcharhinus longimanus, is a circumtropical pelagic shark of high conservation concern (IUCN Red List: “Critically Endangered” in the Western North and Western Central Atlantic and “Vulnerable” globally). I present the first, population genetic assessment of the oceanic whitetip shark on a global scale, based on analysis of two mitochondrial genome regions (entire 1066-1067 bp control region and 784 bp partial ND4 gene), and nine nuclear microsatellite loci. No population structure was detected within the Western Atlantic. However, highly significant population structure was detected between Western Atlantic and Indo-Pacific Ocean sharks across all markers. Additionally, a …

Scalable Parallelization Of A Markov Coalescent Genealogy Sampler, Philip E. Davis

Masters Theses

Coalescent genealogy samplers are effective tools for the study of population genetics. They are used to estimate the historical parameters of a population based upon the sampling of present-day genetic information. A popular approach employs Markov chain Monte Carlo (MCMC) methods. While effective, these methods are very computationally intensive, often taking weeks to run. Although attempts have been made to leverage parallelism in an effort to reduce runtimes, they have not resulted in scalable solutions. Due to the inherently sequential nature of MCMC methods, their performance has suffered diminishing returns when applied to large-scale computing clusters. In the interests of …

A Mitochondrial Dna-Based Computational Model Of The Spread Of Human Populations, Peter Revesz

School of Computing: Faculty Publications

This paper presents a mitochondrial DNA-based computational model of the spread of human populations. The computation model is based on a new measure of the relatedness of two populations that may be both heterogeneous in terms of their set of mtDNA haplogroups. The measure gives an exponentially increasing weight for the similarity of two haplogroups with the number of levels shared in the mtDNA classification tree. In an experiment, the computational model is applied to the study of the relatedness of seven human populations ranging from the Neolithic through the Bronze Age to the present. The human populations included in …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Vanadium Toxicological Potential Versus Its Pharmacological Activity: New Developments And Research, Agnieszka Ścibior, Juan Llopis, Alvin A. Holder, Mario Altamirano-Lozano

Chemistry & Biochemistry Faculty Publications

Scibior, A., Llopis, J., Holder, A. A., & Altamirano-Lozano, M. (2016). Vanadium toxicological potential versus its pharmacological activity: New developments and research. Oxidative Medicine and Cellular Longevity, 2016, 1-2. doi: 10.1155/2016/7612347

Identification Of Lead-Sensitive Expression And Splicing Quantitative Trait Loci In Drosophila Melanogaster By Analysis Of Rna-Seq Data, Wen Qu

Wayne State University Dissertations

Lead exposure has long been one of the most important topics in global public health since it is a potent developmental neurotoxin. Here, we conducted an expression QTL (eQTLs) analysis, which is genome-wide association analysis of genetic variants with differential gene expression, in the male heads of 79 Drosophila melanogaster recombinant inbred lines originally from eight parental strains in the presence or absence of developmental exposure to 250 µM lead acetate. The aim was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs and 952 trans-eQTLs (1000 permutation threshold at …

Sample Size Estimation For Genomics Experiments With Dependent End Points, Desmond Koomson

Open Access Theses & Dissertations

In typical genomics studies involving numerous association tests of gene mutations with a disease, error rate control via multiplicity adjustment is paramount because even if all genes were to be non-differentially associated, we would still make some false positives. Many methods exist that incorporate the control of multiplicity for normally distributed endpoints in sample size estimation, but none addresses the issue for non-normally correlated endpoints.

One common practice in the literature is to assume an equal correlation among all differentially associated or expressed genes, thereby using the generalized binomial or beta-binomial model to compute the comparison-wise power of detecting these …

Apply Data Clustering To Gene Expression Data, Abdullah Jameel Abualhamayl Mr.

Electronic Theses, Projects, and Dissertations

Data clustering plays an important role in effective analysis of gene expression. Although DNA microarray technology facilitates expression monitoring, several challenges arise when dealing with gene expression datasets. Some of these challenges are the enormous number of genes, the dimensionality of the data, and the change of data over time. The genetic groups which are biologically interlinked can be identified through clustering. This project aims to clarify the steps to apply clustering analysis of genes involved in a published dataset. The methodology for this project includes the selection of the dataset representation, the selection of gene datasets, Similarity Matrix Selection, …

Meta-Analysis Of Genome-Wide Association Studies With Correlated Individuals: Application To The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Tamar Sofer, John R. Shaffer, Misa Graff, Qibin Qi, Adrienne M. Stilp, Stephanie M. Gogarten, Kari E. North, Carmen R. Isasi, Cathy C. Laurie, Adam A. Szpiro

UW Biostatistics Working Paper Series

Investigators often meta-analyze multiple genome-wide association studies (GWASs) to increase the power to detect associations of single nucleotide polymorphisms (SNPs) with a trait. Meta-analysis is also performed within a single cohort that is stratified by, e.g., sex or ancestry group. Having correlated individuals among the strata may complicate meta-analyses, limit power, and inflate Type 1 error. For example, in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), sources of correlation include genetic relatedness, shared household, and shared community. We propose a novel mixed-effect model for meta-analysis, “MetaCor", which accounts for correlation between stratum-specific effect estimates. Simulations show that MetaCor controls …

An Incremental Phylogenetic Tree Algorithm Based On Repeated Insertions Of Species, Peter Revesz, Zhiqiang Li

School of Computing: Conference and Workshop Papers

In this paper, we introduce a new phylogenetic tree algorithm that generates phylogenetic trees by repeatedly inserting species one-by-one. The incremental phylogenetic tree algorithm can work on proteins or DNA sequences. Computer experiments show that the new algorithm is better than the commonly used UPGMA and Neighbor Joining algorithms.

A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Gtex Consortium, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im

Bioinformatics Faculty Publications

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys …

Germline Mutation Detection In Next Generation Sequencing Data And Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome, Gang Peng

Dissertations and Theses (Open Access)

Next generation sequencing technology has been widely used in genomic analysis, but its application has been compromised by the missing true variants, especially when these variants are rare. We proposed a family-based variant calling method, FamSeq, integrating Mendelian transmission information with de novo mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real data, FamSeq works better than the single individual based method.

In FamSeq, we implemented four different methods for the Mendelian genetic …

Genetics Of Obesity In Starr County, Texas Mexican Americans, Heather M. Highland

Dissertations and Theses (Open Access)

Currently, over two-thirds of Americans are classified as over-weight or obese. Obesity increases risk for many other diseases including type 2 diabetes, heart disease, stroke, and cancer, making obesity the largest public health problem in America and most other Westernized nations. Hispanics have a higher rate of both obesity and type 2 diabetes, making them a particularly interesting population in which to study obesity. For the last 33 years, the Starr County Health Studies has collected an array of phenotypes and biological samples from residents of Starr County, along Texas-Mexico border. This study includes 825 subjects who were not known …

Heterogeneous Dynamics In Dna Site Discrimination By The Structurally Homologous Dna-Binding Domains Of Ets-Family Transcription Factors, Gaofei He, Ana Tolic, James Bashkin, Gregory Poon

Chemistry & Biochemistry Faculty Works

The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only …

Fisheries Management Paper No.273 - Blue Swimmer Crab Resource Of The Peel-Harvey Estuary Harvest Strategy, 2015-2020. Version 1.0, Department Of Fisheries, Western Australia

Fisheries Management Papers

Harvest strategies for aquatic resources managed by the Western Australian Department of Fisheries (the Department) are formal documents prepared to support the decision-making processes required to ensure the management of these resources are consistent with the principles of Ecologically Sustainable Development (ESD). The objectives of ESD are reflected in the objects of the Fish Resources Management Act 1994 (FRMA), Section 3, and the draft Aquatic Resources Management Bill 2013 (ARMB), Clause 9, which will replace the FRMA once enacted.

The publication of these strategies is intended to make the decision-making considerations and processes for the management of specified aquatic resources …

Expression, Purification, And Activity Of Peptidyl-Trna Hydrolase 1 Of Rickettsia Rickettsii, Jessica Osler

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Proof-Of-Concept Of Environmental Dna Tools For Atlantic Sturgeon Management, Jameson Hinkle

Theses and Dissertations

Abstract

The Atlantic Sturgeon (Acipenser oxyrinchus oxyrinchus, Mitchell) is an anadromous species that spawns in tidal freshwater rivers from Canada to Florida. Overfishing, river sedimentation and alteration of the river bottom have decreased Atlantic Sturgeon populations, and NOAA lists the species as endangered. Ecologists sometimes find it difficult to locate individuals of a species that is rare, endangered or invasive. The need for methods less invasive that can create more resolution of cryptic species presence is necessary. Environmental DNA (eDNA) is a non-invasive means of detecting rare, endangered, or invasive species by isolating nuclear or mitochondrial DNA (mtDNA) from the …

A Meta-Analysis Of Association Between One-Carbon Metabolism Gene Polymorphisms And Risk Of Prostate Cancer, Mahmood Tazari

Walden Dissertations and Doctoral Studies

Prostate cancer is the most common cancer among men. The purpose of this quantitative, meta-analysis study was to examine one-carbon metabolism gene polymorphisms in a group of genes to determine their association with prostate cancer risk. The genetic epidemiology theory provided the framework for the study. The data collected were from published articles. From over 2,800 individual studies, 20 articles were retained for results and data abstraction, following the title, abstract screen, and full text screening in the second phase. The data were analyzed by a meta-analysis statistical method, combining the results from selected studies to estimate the overall association. …

An Assessment Of The Role Of Roads In Population Demography And Genetic Structuring In Two Species Of Lizards In The Northern Chihuahuan Desert, Kevin Floyd

Open Access Theses & Dissertations

Roads can fragment habitat and increase mortality rates of wildlife, potentially reducing population sizes and gene flow, which in turn can reduce genetic diversity through genetic drift. Although negative road impacts have been found in a variety of taxa, not all species are impacted. For instance, species that move less and rarely encounter roads and those that avoid the roads are predicted to not be negatively affected. Yet tests of these predictions are uncommon, especially for reptiles and particularly lizards. Side-blotched lizards (Uta stansburiana) are small sit-and-wait predators, while the larger marbled whiptails (Aspidoscelis marmorata) are active foragers. Their responses …

Testing Gene-Environment Interactions In The Presence Of Measurement Error, Chongzhi Di, Li Hsu, Charles Kooperberg, Alex Reiner, Ross Prentice

UW Biostatistics Working Paper Series

Complex diseases result from an interplay between genetic and environmental risk factors, and it is of great interest to study the gene-environment interaction (GxE) to understand the etiology of complex diseases. Recent developments in genetics field allows one to study GxE systematically. However, one difficulty with GxE arises from the fact that environmental exposures are often measured with error. In this paper, we focus on testing GxE when the environmental exposure E is subject to measurement error. Surprisingly, contrast to the well-established results that the naive test ignoring measurement error is valid in testing the main effects, we find that …

Cloning And Characterization Of Il-1Β, Il-8, Il-10, And Tnfα From Golden Tilefish (Lopholatilus Chamaeleonticeps) And Red Snapper (Lutjanus Campechanus), Kristina L. Deak

USF Tampa Graduate Theses and Dissertations

Cytokines are pleiotropic and redundant signaling molecules that govern the inflammatory response and immunity, a critical ecological parameter for organism success and population growth. Produced at the site of injury or pathogen intrusion by a variety of cell types, cytokines mediate cell-signaling in either an autocrine or paracrine manner. The type and magnitude of the cytokine milieu produced subsequently dictates the strength and form of immune response. As the most diverse vertebrate group, with a high sensitivity to contaminants, fish represent an important foci for the evaluation of immune system evolution, function, and alteration upon toxicant exposure. While many cytokines …

Fisheries Management Paper No.266 - Exmouth Gulf Prawn Managed Fishery Bycatch Action Plan 2014-2019. Version 1.0, Department Of Fisheries, Western Australia

Fisheries Management Papers

Bycatch is described as the part of the catch which is returned to the sea (usually referred to as non-retained or discarded) either because it has no commercial value or because legislative requirements preclude it being retained. Thus, this Bycatch Action Plan (BAP) includes unmarketable finfish and invertebrate species, along with endangered, threatened and protected (ETP) species, such as marine mammals, reptiles and some elasmobranchs.

It is Government policy to minimise bycatch in all commercial fisheries. This BAP details a program of actions to address bycatch issues in the Exmouth Gulf Prawn Managed Fishery (EGPMF), in accordance with the EGPMF …

Scalable Combinatorial Tools For Health Disparities Research, Michael A. Langston, Robert S. Levine, Barbara J. Kilbourne, Gary L. Rogers Jr., Anne D. Kershenbaum, Suzanne H. Baktash, Steven S. Coughlin, Arnold M. Saxton, Vincent K. Agboto, Darryl B. Hood, Maureen Y. Litchveld, Tonny J. Oyana, Patricia Matthews-Juarez, Paul D. Juarez

Sociology Faculty Research

Despite staggering investments made in unraveling the human genome, current estimates suggest that as much as 90% of the variance in cancer and chronic diseases can be attributed to factors outside an individual’s genetic endowment, particularly to environmental exposures experienced across his or her life course. New analytical approaches are clearly required as investigators turn to complicated systems theory and ecological, place-based and life-history perspectives in order to understand more clearly the relationships between social determinants, environmental exposures and health disparities. While traditional data analysis techniques remain foundational to health disparities research, they are easily overwhelmed by the ever-increasing size …

Comparison Of Sequence Alignment Algorithms, Tejas Gandhi

Journal of Undergraduate Research at Minnesota State University, Mankato

The fact that biological sequences can be represented as strings belonging to a finite alphabet (A, C, G, and T for DNA) plays an important role in connecting biology to computer science. String representation allows researchers to apply various string comparison techniques available in computer science. As a result, various applications have been developed that facilitate the task of sequence alignment. The problem of finding sequence alignments consists of finding the best match between two biological sequences. A best match can infer an evolutionary relationship and functional similarity. However, there is a lack of research on how reliable and efficient …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Computational Analysis Of Gene Expression And Connectivity Patterns In The Convoluted Structures Of Mouse Cerebellum, Tao Zeng

Computer Science Theses & Dissertations

One significant difference between evolved mammalian brains and other species is that mammalian brains exhibit increasingly convoluted structures in the cerebral cortex. Groove and ridge shaped structures named gyri and sulci expand surface area of cerebral cortex, making more functions possible. Prior studies using neuroimaging techniques such as dMRI and DTI have revealed that neural fibers are heavily connected to gyri comparing to those connected to sulci, such macro-scale experiments indicates that gyri are involved in large scale information processing while sulci process information locally. However, molecular and cellar level evidences, namely, gene expression pattern and its resulting neuronal connectivity …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations and Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Five Fundamental Gaps In Nature-Nurture Science, Peter J. Taylor

Working Papers on Science in a Changing World

Difficulties identifying causally relevant genetic variants underlying patterns of human variation have been given competing interpretations. The debate is illuminated in this article by drawing attention to the issue of underlying heterogeneity—the possibility that genetic and environmental factors or entities underlying a trait are heterogeneous—as well as four other fundamental gaps in the methods and interpretation of classical quantitative genetics: "Genetic" and "environmental" fractions of variation in traits are distinct from measurable genetic and environmental factors underlying the traits’ development; Standard formulas for partitioning variation in human traits are unreliable; Methods for translation from fractions of variation to measurable …