Genetics Commons^™

Mrub_1304, Mrub_2007 And Mrub_2006 Are Orthologs Of E. Coli B_3189, B_3972, And B_0091, Respectively Within The Peptidoglycan Biosynthesis Pathway, Mylaun E. Griffith, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

No abstract provided.

Mrub_0860, Mrub_0701 And Mrub_2285 Are Orthologous To E. Coli B2892, B2562 And B3863 Within The Recfor Pathway For Homologous Recombination, Bailey Englund, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tool associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict the gene function. We investigated the biological function of the genes Mrub_0860, Mrub_0701,and Mrub_2285. We predicted that Mrub_0860 (DNA coordinates 842934..844868 on the forward strand) encodes for the enzyme single-stranded DNA-specific exonuclease, which is in the first step of homologous recombination via the RecFOR pathway (KEGG map number 03440). The E. coli K12 MG1655 ortholog is predicted to be b2892, which has the gene identifier …

Medical Genetics And Genomic Medicine In The United States. Part 2: Reproductive Genetics, Newborn Screening, Genetic Counseling, Training, And Registries, Debra S. Regier, Carlos Ferreira, Suzanne Hart, Donald Hadley, Maximilian Muenke

Pediatrics Faculty Publications

eview of genetics in the United States with emphasis on the prenatal, metabolic, genetic counseling, and training aspects of the field.

Investigation On Genetic Modifiers Of Age At Onset Of Major Depressive Disorder, Huseyin Gedik

Theses and Dissertations

Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample …

Evolution Of Molt Phenology In Dwarf Hamsters, Zachary Clare-Salzler

Graduate Student Theses, Dissertations, & Professional Papers

Environmental seasonality presents many challenges for survival. In response, organisms from across the tree of life exhibit adaptive phenology, which can facilitate survival from season to season. In particular, many species are white in the winter and brown in the summer where winter snow cover alters the visual environment. There is an extensive body of literature describing the physiological and cellular regulation of this trait in the Siberian dwarf hamster (Phodopus sungorus), but there are major shortcomings in our understanding concerning the evolution and molecular regulation of mammalian skin phenology. Notably, little is known about the genetic basis …

Evolution In Light Of Mitonuclear Landscapes: An Examination Of Mitochondrial Replacement In Killifish (Fundulus Spp.), Stephen D. Flanagan

Dissertations

The mitochondria are responsible for the bulk of energy production in eukaryotes. They possess their own genome that works in conjunction with the nuclear genome to accomplish the extraordinarily important task of energy conversion. When species hybridize there will be a mismatch in evolutionary histories between these two genomes. The deleterious interactions of these genomes have been studied in great detail (i.e. hybrid breakdown). However, little work has been conducted to understand the population genetic, and morphological consequences of wide-ranging replacement. The Fundulus notatus complex is comprised of 3 species: F. notatus, F. olivaceus, and F. euryzonus. …

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder

Dissertations and Theses (Open Access)

Over the last decade, a paradigm-shift in lung cancer therapy has evolved into targeted-driven medicinal approaches. However, patients frequently relapse and develop resistance to available therapies. Herein, we utilized genomic mutation data from advanced chemorefractory non-small cell lung cancer (NSCLC) patients enrolled in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) clinical trial to characterize novel actionable genomic alterations potentially of clinical relevance. We identified RICTOR alterations (mutations, amplifications) in 17% of lung adenocarcinomas and found RICTOR expression correlates to worse overall survival. There was enrichment of MAPK pathway genetic aberrations in key oncogenes (e.g. KRAS, BRAF, …

Characterization, Development And Multiplexing Of Microsatellite Markers In Three Commercially Exploited Reef Fish And Their Application For Stock Identification, Laura Taillebois, Christine Dudgeon, Safia Maher, David Crook, Thor Saunders, Diane P. Barton, Jonathan A. Taylor, David J. Welch, Stephen J. Newman, Michael J. Travers, Richard J. Saunders, Jennifer Ovenden

Fisheries Research Articles

Thirty-four microsatellite loci were isolated from three reef fish species; golden snapper Lutjanus johnii, blackspotted croaker Protonibea diacanthus and grass emperor Lethrinus laticaudis using a next generation sequencing approach. Both IonTorrent single reads and Illumina MiSeq paired-end reads were used, with the latter demonstrating a higher quality of reads than the IonTorrent. From the 1–1.5 million raw reads per species, we successfully obtained 10–13 polymorphic loci for each species, which satisfied stringent design criteria. We developed multiplex panels for the amplification of the golden snapper and the blackspotted croaker loci, as well as post-amplification pooling panels for the grass …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

Development Of Genomic Resources For The Evaluation Of Red Snapper, An Emerging Species Candidate For Marine Aquaculture And Stock Enhancement, Adrienne Elise Norrell

Master's Theses

The northern red snapper (Lutjanus campechanus) is a highly targeted reef fish candidate for marine aquaculture and stock enhancement in the southern United States. This work aimed to develop genomic resources for the genetic management of aquaculture programs and to investigate population structure using high-throughput sequencing technologies. Eighty-four new microsatellite markers were developed through screening of Illumina paired-end sequencing reads. Microsatellite loci and Single Nucleotide Polymorphisms (SNPs) generated through Restriction Site Associated DNA (RAD) sequencing were assayed in 5 outbred full-sib families to construct a high-density linkage map of the red snapper genome. The map consists of 7,964 …

Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff

Dissertations and Theses (Open Access)

Gene content determination and variant calling in the complex KIR genomic region are useful for immune system function analysis, pathogenesis and disease risk factor elucidation, immunotherapy development, evolutionary investigations, and human migration modeling. Sequence-specific oligonucleotide and sequence-specific primer PCR methods are the de facto standards for KIR presence/absence identification, but the current platforms are unsuitable for SNP calling, impractical for KIR typing large cohorts of DNA samples, and inapplicable for typing repositories in which sequence data, but not cells or cell analytes, are available. Alternative typing methods, such as in silico sequence-based typing, can address the problems associated with amplicon-based …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Tropical Trees As Islands: Diversity Accumulation Of Armored Scale Insects (Hemiptera: Diaspididae) On Trees As A Function Of Forest Age, Hannah Shapiro

Undergraduate Honors Theses

Armored scale insects (Hemiptera: Diaspididae) are some of the most invasive insects in the world. These cryptic plant parasites are most often encountered in managed agricultural ecosystems, but very little is known about their distribution, abundance, and diversity in tropical rainforest canopies, where they are likely to have their highest diversity. Because these ubiquitous insects are extreme generalists with undirected dispersal, their diversity (alpha and beta) accumulation can conceivably be modeled according to tenets derived from island biogeography theory. For example, one expectation is that older established trees should boast a higher species diversity and abundance than younger ones. Other …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Mrub_2874 Is Homologous To B3386 And Mrub_1349 Is Homologous To B2914, But Mrub_1349 Is Not Homologous To B4090, Samantha Murad, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

ABSTRACT. This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2874 and Mrub_1349. We predict that Mrub_2874 encodes the enzyme ribulose-5-phosphate 3-epimerase (DNA coordinates 2912530..2913204 on the reverse strand), which is the first step of the pentose phosphate pathway (KEGG map number 00030). It catalyzes the conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate. The E. coli K12 MG1655 ortholog is predicted to be b3386, which has the gene …

Comparing Meiothermus Ruber And Myxococcus Xanthus In The Purine Metabolism Pathway, Linnea J. Ritchie, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. I investigated the biological functions of Mrub_1053 Mrub_2281 and Mrub_2299. I predicted that Mrub_1053 and Mrub_2281 (DNA coordinates 1053364..1054359 on the forward strand and 2333172..2334113 on the forward strand respectively) encodes the enzyme phosphoribose-1-pyrophosphate synthetase (PRS) which is the first step of the purine synthesis pathway (KEGG). I also predicted that Mrub_2299 (DNA coordinates: 2352378..2353775 on the forward strand) encodes for Phosphoribosyl pyrophosphate (PRPP) amidotransferase, which is …

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 …

Genetic And Genomic Basis Of Antibody Response To Porcine Reproductive And Respiratory Syndrome (Prrs) In Gilts And Sows, Nick V. Serão, Robert A. Kemp, Benny Mote, Philip Willson, John C.S. Harding, Stephen C. Bishop, Graham S. Plastow, Jack C.M. Dekkers

Department of Animal Science: Faculty Publications

Background: Our recent research showed that antibody response to porcine reproductive and respiratory syndrome (PRRS), measured as sample-to-positive (S/P) ratio, is highly heritable and has a high genetic correlation with reproductive performance during a PRRS outbreak. Two major quantitative trait loci (QTL) on Sus scrofa chromosome 7 (SSC7; QTL_MHC and QTL₁₃₀) accounted for ~40 % of the genetic variance for S/P. Objectives of this study were to estimate genetic parameters for PRRS S/P in gilts during acclimation, identify regions associated with S/P, and evaluate the accuracy of genomic prediction of S/P across populations with different prevalences of …

Phenotypic And Genetic Analyses Of Adaptation To Geothermal Soils In Yellow Monkeyflowers Of Yellowstone National Park, Peter Breigenzer

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Microgeographic adaptation, which occurs on a spatial scale smaller than the dispersal distance of the evolving organisms, provides a fertile context for understanding the genetic processes that shape natural variation and contribute to biological diversity. In plants, mosaics of distinct soil conditions can select for microgeographic divergence in the face of gene flow, leading to major life history transitions and novel trait evolution. Mimulus (monkeyflowers) is an emerging model genus for ecological genomics, due to tremendous diversity, experimental tractability, and a wealth of genomic resources. In Yellowstone National Park, Mimulus guttatus occurs in both geothermal soils and nearby nonthermal bogs …

Investigating The Molecular Etiologies Of Sporadic Als (Sals) Using Rna-Sequencing, David G. Brohawn

Theses and Dissertations

ALS is an often lethal disease involving degeneration of motor neurons in the brain and spinal cord. Current treatments only extend life by several months, and novel therapies are needed. We combined RNA-Sequencing, systems biology analyses, and molecular biology assays to elucidate sporadic ALS group-specific differences in postmortem cervical spinal sections (7 sALS and 8 control samples) that may be relevant to disease pathology. >55 million 2X150 RNA-sequencing reads per sample were generated and processed.

In Chapter 2, we used bioinformatics tools to identify nuclear differentially expressed genes (DEGs) between our two groups. Further, we used Weighted Gene Co-Expression Network …

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 …

Population Genetic Structure Of Necturus Maculosus In Central And Eastern Kentucky, Mason Owen Murphy

Theses and Dissertations--Biology

Population structure is influenced by extrinsic factors, such as landscape architecture and dispersal barriers. Lotic network architecture is known to constrain ecological, demographic and evolutionary processes, including population genetic structure. I assessed the population structure of a widespread aquatic salamander, Necturus maculosus, across three river basins in central and eastern Kentucky. I examined the role of network architecture, anthropogenic barriers, and spatial scale on patterns of population structure. I also provided a review of N. maculosus capture methods and offer an improved trap design. I identified significant structuring between the combined Licking/Kinniconick basin and the Kentucky River basin, with …

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 …

An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien

Honors Scholar Theses

In recent years, several new clades within the domain Achaea have been discovered. This is due in part to microbiological sampling of novel environments, and the increasing ability to detect and sequence uncultivable organisms through metagenomic analysis. These organisms share certain features, such as small cell size and streamlined genomes. Reduction in genome size can present difficulties to phylogenetic reconstruction programs. Since there is less genetic data to work with, these organisms often have missing genes in concatenated multiple sequence alignments. Evolutionary Biologists have not reached a consensus on the placement of these lineages in the archaeal evolutionary tree. There …

Using High Throughput Genomic Sequencing To Predict Ecological Impacts On Sea Turtle Populations, Lesley Anderson

STAR Program Research Presentations

Marine turtles are long-lived, migratory vertebrates that encounter a variety of human and natural stressors throughout their lives. Understanding the biology and threats of these animals is challenging because they are hard to observe, and can migrate across whole ocean basins. Minimally invasive sampling techniques (e.g., blood samples) allow us to learn about their physiology, genetics, and the environmental conditions they have experienced. In this project, we developed a novel method to extract the RNA from whole green and loggerhead turtle blood from animals inhabiting a variety of sites across the Pacific Ocean. Some habitats are more pristine, while others …

Characterization Of Putative Wnt3a-Inducible Enhancers, Katelynn C. Lee, Nicholas Hum, Aimy Sebastian, Gabriela Loots

STAR Program Research Presentations

The Wnt signaling pathway has been previously shown to play a major role in regulating bone metabolism and it is emerging as a target for the therapeutic intervention of bone thinning disorders such as osteoporosis. Several Wnt proteins have been shown to be expressed in bone and mutations in Wnt pathway members such as Wnt co-receptor Lrp5 and Wnt inhibitor Sost have been shown to be associated with low or high bone mass disorders, however, very little is known about specific roles played by different Wnt ligands in bone development, repair and remodeling. To identify downstream targets of Wnt signaling …

Identification Of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing, Timothy B. Palculict

Dissertations and Theses (Open Access)

Wilms tumor, a childhood tumor arising from undifferentiated renal mesenchyme, is diagnosed in North America at a frequency of 1 in 10,000 live births and accounts for 5% of all pediatric cancers. The etiology of Wilms tumor is heterogeneous with multiple genes known to have an effect on Wilms tumor development; however, these genes are rarely associated with familial Wilms tumor. Gene mutations in WT1, WTX, CTNNB1 and TP53 are observed in a third of sporadic tumors, while the causative gene(s) responsible for familial Wilms tumor are largely unknown. Approximately 2% of Wilms tumor patients have a family …

Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li

Dissertations and Theses (Open Access)

A typical human exome harbors dozens of loss-of-function (LOF) variants predicted to severely disrupt or abolish gene function. These variants are enriched at the extremely rare end of the allele frequency spectrum (< 0.1%), suggesting purifying selection against these sites. However, most previous population-based sequencing studies have not included analysis of genotype-phenotype relationships with LOF variants. Thus, the contribution of LOF variation to health and disease within the general population remains largely uncharacterized.

Using whole exome sequence from 8,554 participants in the Atherosclerosis Risk in Communities (ARIC) study, we explored the impact of LOF variation on a broad spectrum of human phenotypes. First, we selected 20 common chronic disease risk factor phenotypes and performed gene-based association tests. Analysis of this sample verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Novel relationships included …

Mutations That Separate The Functions Of The Proofreading Subunit Of The Escherichia Coli Replicase, Zakiya Whatley, Kenneth N. Kreuzer

Biology Faculty Publications

The dnaQ gene of Escherichia coli encodes the Ɛ subunit of DNA polymerase III, which provides the 3' - 5' exonuclease proofreading activity of the replicative polymerase. Prior studies have shown that loss of Ɛ leads to high mutation frequency, partially constitutive SOS, and poor growth. In addition, a previous study from our laboratory identified dnaQ knockout mutants in a screen for mutants specifically defective in the SOS response after quinolone (nalidixic acid) treatment. To explain these results, we propose a model whereby, in addition to proofreading, Ɛ plays a distinct role in replisome disassembly and/or processing of stalled replication …

Mongolians In The Genetic Landscape Of Central Asia: Exploring The Genetic Relations Among Mongolians And Other World Populations, Jane E. Brissenden, Judith R. Kidd, Baigalmaa Evsanaa, Ariunaa Togtokh, Andrew J. Pakstis, Françoise Friedlaender, Kenneth K. Kidd, Janet M. Roscoe

Human Biology Open Access Pre-Prints

Genetic data on North Central Asian populations are underrepresented in the literature, especially autosomal markers. In the present study we use 812 single nucleotide polymorphisms that are distributed across all the human autosomes and that have been extensively studied at Yale to examine the affinities of two recently collected, samples of populations: rural and cosmopolitan Mongolians from Ulaanbaatar and nomadic, Turkic-speaking Tsaatan from Mongolia near the Siberian border. We compare these two populations to one another and to a global set of populations and discuss their relationships to New World populations. Specifically, we analyze data on 521 autosomal loci (single …