Genetics and Genomics Commons^™

Chlorovirus Pbcv-1 Encodes An Active Copper-Zinc Superoxide Dismutase, Ming Kang, Garry A. Duncan, Charles Kuszynski, George Oyler, Jiayin Zheng, Donald F. Becker, James L. Van Etten

James Van Etten Publications

Superoxide dismutases (SODs) are metalloproteins that protect organisms from toxic reactive oxygen species by catalyzing the conversion of superoxide anion to hydrogen peroxide and molecular oxygen. Chlorovirus PBCV-1 encodes a 187-amino-acid protein that resembles a Cu-Zn SOD with all of the conserved amino acid residues for binding copper and zinc (named cvSOD). cvSOD has an internal Met that results in a 165-amino-acid protein (named tcvSOD). Both cvSOD and tcvSOD recombinant proteins inhibited nitroblue tetrazolium reduction of superoxide anion generated in a xanthine-xanthine oxidase system in solution. tcvSOD was chosen for further characterization because it was easier to produce. Recombinant tcvSOD …

The Evolution Of Genomic Imprinting: Theories, Predictions And Empirical Tests, M M. Patten, L Ross, J P. Curley, David C. Queller, R Bonduriansky, J B. Wolf

Biology Faculty Research

The epigenetic phenomenon of genomic imprinting has motivated the development of numerous theories for its evolutionary origins and genomic distribution. In this review, we examine the three theories that have best withstood theoretical and empirical scrutiny. These are: Haig and colleagues’ kinship theory; Day and Bonduriansky’s sexual antagonism theory; and Wolf and Hager’s maternal–offspring coadaptation theory. These theories have fundamentally different perspectives on the adaptive significance of imprinting. The kinship theory views imprinting as a mechanism to change gene dosage, with imprinting evolving because of the differential effect that gene dosage has on the fitness of matrilineal and patrilineal relatives. …

Rna Interference As A Tool For The Functional Analysis Of Genes In The Colorado Potato Beetle, Leptinotarsa Decemlineata (Say), Ashley Danielle Yates

Department of Entomology: Dissertations, Theses, and Student Research

RNA interference (RNAi) is a naturally occurring phenomenon in eukaryotes in which a double-stranded RNA (dsRNA) suppresses the expression of a target gene. RNAi has markedly changed the way in which functional genetics studies are performed, especially in non-model organisms. In insects, the efficacy of RNAi is influenced by several factors, including the species and the methods of dsRNAs delivery.

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is a pest of the plant family Solanaceae. RNAi in the CPB is of interest for potential use in insect management and as a tool to study the interaction with host plants. …

General Approaches For Combining Multiple Rare Variant Associate Tests Provide Improved Power Across A Wider Range Of Genetic Architecture, Nathan L. Tintle, Brian Greco, Allison Hainline, Keli Liu, Jaron Arbet, Alejandra Benitez, Kelsey Grinde

Faculty Work Comprehensive List

In the wake of the widespread availability of genome sequencing data made possible by way of nextgeneration technologies, a flood of gene‐based rare variant tests have been proposed. Most methods claim superior power against particular genetic architectures. However, an important practical issue remains for the applied researcher—namely, which test should be used for a particular association study which may consider multiple genes and/or multiple phenotypes. Recently, tests have been proposed which combine individual tests to minimize power loss while improving the robustness to a wide range of genetic architectures. In our analysis, we propose an expansion of these approaches, by …

Characterizing Populations Of Non-Coding Rnas In Karenia Brevis At Different Times Of The Diel Cycle, Scott Boyd Anglin

Master's Theses

Karenia brevis is a mixotrophic, marine dinoflagellate found in the Gulf of Mexico that generates periodic, if not annual, harmful algal blooms (also known as “red tides”) in certain coastal areas. In an effort to better understand the biology of this organism, a functional genomics project has been initiated. As part of that project, it has been determined that a significant number of natural antisense transcripts (NATs) as well as double-stranded RNA (dsRNA) molecules exist within the transcriptome of K. brevis. I hypothesize that the non-coding NATs, similar to microRNAs (miRNAs) in other organisms play a role in regulating …

Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller

Dissertations and Theses (Open Access)

The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a …

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 …

Development Of Chimeric Type Iv Secretion Systems For Transfer Of Heterologous Substrates Across The Gram-Negative Cell Envelope, Trista M. Berry

Dissertations and Theses (Open Access)

Many bacteria use Type IV Secretion Systems (T4SSs) to aid in pathogenesis by translocating virulence factors across the cell envelope and into eukaryotic cells. These systems are structurally and functionally diverse, but are often compared to the archetypal VirB/VirD4 T4SS of Agrobacterium tumefaciens. This system is composed of the VirD4 type IV coupling protein (T4CP) and 11 VirB subunits (VirB1-11) that assemble as the secretion channel and an extracellular pilus. The T4CP is an inner membrane ATPase that interacts with T4SS substrates and the secretion channel, and is thought to link substrates with the secretion channel and possibly energize …

Utilizing Haplotypes For Sensitive Snp Array-Based Discovery Of Somatic Chromosomal Mutations, Selina M. Vattathil

Dissertations and Theses (Open Access)

Somatic copy-number (CN) gains and losses and copy-neutral loss of heterozygosity (CNLOH) frequently occur in tumors and play a major role in the progression of disease by altering gene dosage and unmasking deleterious recessive variants. Characterizing these mutations in an individual tumor sample is therefore critical for research on the relationship of specific mutations to disease outcome and for clinical decision-making based on mutations with known impact. A pervasive hindrance to sensitive detection of these mutations is genetic heterogeneity and high levels of contaminating normal cells in tumor samples, which limit the fraction of cells carrying informative mutations. The method …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations and Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations and Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Development Of A Molecular Gram-Stain Assay For The Diagnosis Of Blood Stream Infections Associated With Sepsis, Douglas Bryan Litwin

Dissertations and Theses (Open Access)

Sepsis is a serious medical condition resulting from the severe dysregulation of the immune response that is generally triggered by infection. It affects more than 1.1 million Americans, has an average mortality rate of 30%, and is estimated to cost $24.3 billion annually. Currently, blood culture followed by Gram-stain analysis is the gold standard for diagnosing bacterial infections associated with sepsis. This method generates a high rate of false negative results and, in general, requires 20 to 48 hr to provide results. Both of these problems are related to the requirement that the bacterial pathogens grow under defined laboratory conditions. …

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Graduate Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important …

Sheep Updates 2014, James Kynge, David Lindsay, Johan Greeff, John Young, Luke Stephen, Graham Gardner, Stephen Lee, Bindi Murray, James Rowe

Sheep Updates

This session covers nine papers from different authors:

Genetic Research: A brave new world of opportunities

1. "China's Appetite" - The implications for WA, James Kynge, Chairman, FT Confidential Research, Emerging Markets Editor, Financial Times, London.

2. The genetics warm-up - the secret language of genetic research and its impacts on WA's sheep flock, Professor David Lindsay, University of Western Australia, Perth WA

The strength of genetic data: is it really valuable?

3. Genetic research in Western Australia - What have the compromises in production been? Johan Greeff, Senior Geneticist, Department of Agriculture and Food Western Australia

4. Show …

An Exploration Of Fern Genome Space, Paul G. Wolf, Emily B. Sessa, D. Blaine Marchant, Fay-Wei Li, Carl J. Rothfels, Erin M. Sigel, Mathew A. Gitzendanner, Clayton J. Visger, Jo Ann Banks, Douglas E. Soltis, Pamela S. Soltis, Kathleen M. Pryer, Joshua P. Der

An Exploration of Fern Genome Space

Ferns are one of the few remaining major clades of land plants for which a complete genome sequence is lacking. Knowledge of genome space in ferns will enable broad-scale comparative analyses of land plant genes and genomes, provide insights into genome evolution across green plants, and shed light on genetic and genomic features that characterize ferns, such as their high chromosome numbers and large genome sizes. As part of an initial exploration into fern genome space, we used a whole genome shotgun sequencing approach to obtain low-density coverage (1X to 2X) for six fern species from the Polypodiales (Ceratopteris …

Metagenomic Identification Of A Novel Salt Tolerance Gene From The Human Gut Microbiome Which Encodes A Membrane Protein With Homology To A Brp/Blh-Family Beta-Carotene 15,15'-Monooxygenase, Eamonn P. Culligan, Roy D. Sleator, Julian R. Marchesi, Colin Hill

Department of Biological Sciences Publications

The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane.

Collective Behaviour Without Collective Order In Wild Swarms Of Midges, Alessandro Attanasi, Andrea Cavagna, Lorenzo Del Castello, Irene Giardina, Stefania Melillo, Leonardo Parisi, Oliver Pohl, Bruno Rossaro, Edward Shen, Edmondo Silvestri, Massimilano Viale

Publications and Research

Collective behaviour is a widespread phenomenon in biology, cutting through a huge span of scales, from cell colonies up to bird flocks and fish schools. The most prominent trait of collective behaviour is the emergence of global order: individuals synchronize their states, giving the stunning impression that the group behaves as one. In many biological systems, though, it is unclear whether global order is present. A paradigmatic case is that of insect swarms, whose erratic movements seem to suggest that group formation is a mere epiphenomenon of the independent interaction of each individual with an external landmark. In these cases, …

Population And Demographic Structure Of Ixodes Scapularis Say In The Eastern United States., Joyce M. Sakamoto, Jerome Goddard, Jason L. Rasgon

CALS Publications

INTRODUCTION: The most significant vector of tick-borne pathogens in the United States is Ixodes scapularis Say (the blacklegged tick). Previous studies have identified significant genetic, behavioral and morphological differences between northern vs. southern populations of this tick. Because tick-borne pathogens are dependent on their vectors for transmission, a baseline understanding of the vector population structure is crucial to determining the risks and epidemiology of pathogen transmission. METHODS: We investigated population genetic variation of I. scapularis populations in the eastern United States using a multilocus approach. We sequenced and analyzed the mitochondrial COI and 16S genes and three nuclear genes (serpin2, …

Regulation Of Strand-Specific Processing In Human Pre-Mir-371 And Its Mouse Homologs, Jianting Shi

Graduate School of Biomedical Sciences Theses and Dissertations

MicroRNAs (miRNAs) are small noncoding RNAs, known to regulate genes by inducing target mRNA degradation or translational repression. This regulatory function has been shown to assist developmental timing control and increasingly more evidence reveals some of the miRNAs may have tissue/cell type-specific function, showing the potential to assist cell differentiation. Mouse miR-290-295 cluster is embryonic stem cell (ESCs)-specific miRNA cluster and human miR-371-373 cluster has been verified to be its functional homolog. We have previously demonstrated that human pre-miR-371 is processed into multiple miRNA species, which represent the seeds of the mouse of miR-290-5p, miR-292-5p, miR-292-3p-iso2 and miR-293-3p. Deep sequencing …

The Search, The Jackson Laboratory

Search Magazine

No abstract provided.

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated …

Expression Of Chlorovirus Mt325 Aquaglyceroporin (Aqpv1) In Tobacco And Its Role In Mitigating Drought Stress, Saadia Bihmidine, Mingxia Cao, Ming Kang, Tala Awada, James L. Van Etten, David Dunigan, Thomas E. Clemente

James Van Etten Publications

Main conclusions A Chlorovirus aquaglyceroporin expressed in tobacco is localized to the plastid and plasma membranes. Transgenic events display improved response to water deficit. Necrosis in adult stage plants is observed.

Aquaglyceroporins are a subclass of the water channel aquaporin proteins (AQPs) that transport glycerol along with other small molecules transcellular in addition to water. In the studies communicated herein, we analyzed the expression of the aquaglyceroporin gene designated, aqpv1, from Chlorovirus MT325, in tobacco (Nicotiana tabacum), along with phenotypic changes induced by aqpv1 expression in planta. Interestingly, aqpv1 expression under control of either a constitutive or …

Functional Genomics Of Maize Endosperm Maturation And Protein Quality, Lingling Yuan

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Maize is one of the most important cereal crops and widely cultivated throughout the world. The study on maize kernel development including protein quality improvement is essential for removing dietary protein deficiency because of the lack of essential amino acids, especially lysine and tryptophan, in maize kernel. Quality Protein Maize (QPM) is a hard kernel variant of the high-lysine mutant, opaque-2. We created opaque QPM variants to identify opaque-2 modifier genes and to investigate deletion mutagenesis combined with Illumina sequencing as a maize functional genomics tool. A K0326Y-QPM deletion mutant, line 107, was null for the 27- and 50-kD …

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …

The Dynamic Proliferation Of Cansines Mirrors The Complex Evolution Of Feliforms, Kathryn B. Walters-Conte, Diana L. E. Johnson, Warren E. Johnson, Stephen J. O'Brien, Jill Pecon-Slattery

Biology Faculty Articles

Background: Repetitive short interspersed elements (SINEs) are retrotransposons ubiquitous in mammalian genomes and are highly informative markers to identify species and phylogenetic associations. Of these, SINEs unique to the order Carnivora (CanSINEs) yield novel insights on genome evolution in domestic dogs and cats, but less is known about their role in related carnivores. In particular, genome-wide assessment of CanSINE evolution has yet to be completed across the Feliformia (cat-like) suborder of Carnivora. Within Feliformia, the cat family Felidae is composed of 37 species and numerous subspecies organized into eight monophyletic lineages that likely arose 10 million years ago. Using …

Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels And Status Of Regional Lymph Nodes In Patients With Sporadic Colorectal Cancer From Southern China, Yu Liang, Weizhong Tang, Tiquiang Huang, Yong Gao, Aihua Tan, Xiaobo Yang, Haiying Zhang, Yanling Hu, Xue Qin, Shan Li, Shijun Zhang, Linjian Mo, Zhenjia Liang, Deyi Shi, Zhang Huang, Yingyong Guan, Jicheng Zhou, Cheryl Winkler, Stephen J. O'Brien, Jianfeng Xu, Zengnan Mo, Tao Peng

Marine & Environmental Sciences Faculty Articles

Background:  Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications.

Methods and Findings:  Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI …

Evaluation Of The Power And Type 1 Error Of Recently Proposed Family-Based Tests Of Assocations For Rare Variants, Allison Hainline, Carolina Alvarez, Alexander Luedtke, Brian Greco, Andrew Beck, Nathan L. Tintle

Faculty Work Comprehensive List

Until very recently, few methods existed to analyze rare-variant association with binary phenotypes in complex pedigrees. We consider a set of recently proposed methods applied to the simulated and real hypertension phenotype as part of the Genetic Analysis Workshop 18. Minimal power of the methods is observed for genes containing variants with weak effects on the phenotype. Application of the methods to the real hypertension phenotype yielded no genes meeting a strict Bonferroni cutoff of significance. Some prior literature connects 3 of the 5 most associated genes (p <1 × 10−4) to hypertension or related phenotypes. Further methodological development is needed to extend these methods to handle covariates, and to explore more powerful test alternatives.

Evaluating The Concordance Between Sequencing, Imputation And Microarray Genotype Calls In The Gaw18 Data, Ally Rogers, Andrew Beck, Nathan L. Tintle

Faculty Work Comprehensive List

Genotype errors are well known to increase type I errors and/or decrease power in related tests of genotypephenotype association, depending on whether the genotype error mechanism is associated with the phenotype. These relationships hold for both single and multimarker tests of genotype-phenotype association. To assess the potential for genotype errors in Genetic Analysis Workshop 18 (GAW18) data, where no gold standard genotype calls are available, we explored concordance rates between sequencing, imputation, and microarray genotype calls. Our analysis shows that missing data rates for sequenced individuals are high and that there is a modest amount of called genotype discordance between …

Genetic Analysis Workshop 18: Methods And Strategies For Analyzing Human Sequence And Phenotype Data In Members Of Extended Pedigrees, Heike Bickeboller, Julia N. Bailey, Joseph Beyene, Rita M. Cantor, Heather J. Cordell, Robert C. Culverhouse, Corinne D. Engelman, David W. Fardo, Saurabh Ghosh, Inke R. Konig, Justo Lorenzo Bermejo, Phillip E. Melton, Stephanie A. Santorico, Glen A. Satten, Lei Sun, Nathan L. Tintle, Andreas Ziegler, Jean W. Maccluer, Laura Almasy

Faculty Work Comprehensive List

Genetic Analysis Workshop 18 provided a platform for developing and evaluating statistical methods to analyze whole-genome sequence data from a pedigree-based sample. In this article we present an overview of the data sets and the contributions that analyzed these data. The family data, donated by the Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Ethnic Samples Consortium, included sequence-level genotypes based on sequencing and imputation, genome-wide association genotypes from prior genotyping arrays, and phenotypes from longitudinal assessments. The contributions from individual research groups were extensively discussed before, during, and after the workshop in theme-based discussion groups before being submitted …

Application Of Family-Based Tests Of Association For Rare Variants To Pathways, Brian Greco, Alexander Luedtke, Allison Hainline, Carolina Alvarez, Andrew Beck, Nathan L. Tintle

Faculty Work Comprehensive List

Pathway analysis approaches for sequence data typically either operate in a single stage (all variants within all genes in the pathway are combined into a single, very large set of variants that can then be analyzed using standard “gene-based” test statistics) or in 2-stages (gene-based p values are computed for all genes in the pathway, and then the gene-based p values are combined into a single pathway p value). To date, little consideration has been given to the performance of gene-based tests (typically designed for a smaller number of single-nucleotide variants [SNVs]) when the number of SNVs in the gene …