Genetics and Genomics Commons^™

Dna Secondary Structures And Their Contribution To Mutagenesis In B. Subtilis Stationary Phase Cells, Carmen Vallin, Katherine Ona, Chris Ross, Ronald E. Yasbin, Eduardo A. Robleto

Undergraduate Research Opportunities Program (UROP)

It is widely known and accepted that the cause of many mutations in cells are generated during the replication process of actively dividing cells, however more recent research has shown that mutations also arise in non growing conditions, a phenomenon known stationary phase mutagenesis. Much of what is known come from studies in eukaryotic and bacterial models. It is proposed that in nongrowing cells, the process of transcription plays an important role in mutagenesis. I will test the hypothesis that secondary structures formed of DNA generated transcription promote mutagenesis. The sequences transcriptiongenerated structures are speculated to be prone to mutations …

Stationary Phase Mutagenesis In Bacillus Subtilis: The Interaction Between Transcription And Error-Prone Replication In Conditions Of Stress, Mary Girard, Eduardo Robleto

Undergraduate Research Opportunities Program (UROP)

While under conditions of stress, non-dividing cells may acquire beneficial mutations. This is referred to as stationary phase mutagenesis, or adaptive mutagenesis. Previous research has shown that actively transcribed genes and those under selective pressure are prone to mutations that confer escape from non-dividing conditions. Accordingly, strains lacking transcription factors have shown a drastically lower number of mutations that confer escape while under amino acid starvation than those observed in the wildtype background. Also, error-prone DNA polymerases are known to be active in cells under stress and it has been shown that strains lacking an error-prone DNA polymerase display reduced …

Bridging Functional Genomics And Toxicogenomics Through Dna Microarrays In A Fish Model, Shuzhao Li

Dissertations

In a case study of finding gene expression signatures for environmental stressors in Cyprinodon variegatus, this dissertation examines several important issues of applying DNA microarray technology to fish toxicogenomics. The most relevant disciplines, fish toxicogenomics and computational systems biology are reviewed in Chapter 1. Chapter 2 reviews major aspects of DNA microarray technology.

On DNA microarrays, even for probes that target the same transcript, large variations are seen in the probe signals. These variations are partly dependent and partly independent on probe sequences. Chapter 3 estimates the sequence independent variation by combining experimental and computational approaches. Chapter 4 and …

Searching For The Binding Partners For The Novel Phkg1 Variant Γ 181, Kishore Polireddy

Masters Theses & Specialist Projects

No abstract provided.

Fisheries Management Paper No.245 - Aquaculture Of Coral, Live Rocks And Associated Products. Aquaculture Policy, Department Of Fisheries, Western Australia

Fisheries Management Papers

Aquarium enthusiasts use corals, live rock and associated products (e.g. live sand) for display and to maintain healthy water quality conditions in their marine aquariums. There is a large and growing market for these products. While the wild harvest fisheries for aquarium products in Western Australia are sustainably managed, output is capped, so increased product is needed to meet the market demand. With a trend towards the capping of wild harvest and additional pressures, such as the introduction of Marine Parks and other marine protected areas, the aquaculture of these products is set for industry development and expansion.

The large …

Adding Upstream Sequence And A Downstream Reporter To The Bile Acid Inducible Promoter Of Clostridium Scindens Vpi 12708, Bryan Patrick Mason

Masters Theses & Specialist Projects

Bile acids in the small intestines of animals serve to breakdown fats and fatsoluble vitamins. Most of the bile acids are reabsorbed into the enterohepatic circulation, but approximately five percent of these bile acids pass into the large intestine. These bile acids are swiftly deconjugated by the bacterial population, and then subjected to further intestinal bacterial chemical modifications. The most significant of these modifications are 7α-dehydroxylations which form secondary bile acids (deoxycholate and lithocholate). Much research has illuminated the 7α-dehydroxylation pathway: of particular interest is the bile acid inducible operon, for which Clostridium scindens VPI 12708 serves as the model …

Rapid Evolution Of Sex-Pheromone-Producing Enzyme In Drosophila, Troy R. Shirangi, Héloïse D. Dufour, Thomas M. Williams, Sean B. Carroll

Biology Faculty Publications

A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We …

Trio Logic Regression - Detection Of Snp - Snp Interactions In Case-Parent Trios, Qing Li, Thomas A. Louis, M. Daniele Fallin, Ingo Ruczinski

Johns Hopkins University, Dept. of Biostatistics Working Papers

Statistical approaches to evaluate higher order SNP-SNP and SNP-environment interactions are critical in genetic association studies, as susceptibility to complex disease is likely to be related to the interaction of multiple SNPs and environmental factors. Logic regression (Kooperberg et al., 2001; Ruczinski et al., 2003) is one such approach, where interactions between SNPs and environmental variables are assessed in a regression framework, and interactions become part of the model search space. In this manuscript we extend the logic regression methodology, originally developed for cohort and case-control studies, for studies of trios with affected probands. Trio logic regression accounts for the …

Investigating The Roles Of Ndj1 And Tid1 In Distributive Segregation Using Non-Exchange Chromosomes, Jonathan V. Henzel

Master's Theses

Meiosis is a specialized cell division that leads to a reduction of ploidy in sexually reproducing organisms through segregation of homologous chromosomes at the first meiotic division. Improper segregation of chromosomes during meiosis results in anueploidy, which is usually fatal during embryonic development. The meiotic process is therefore tightly regulated. Typically, proper segregation of homologs at meiosis I requires pairing of homologous chromosomes, followed by crossover recombination between homologs. Crossovers enable proper chromosomal segregation during the first meiotic division in part by establishing tension in the meiotic spindle. However, in the absence of crossovers, some cells maintain the ability to …

Spatial Patterns, Population Genetics, And Multiple Paternity Of The Freshwater Mussel Villosa Iris, (Lea 1829), Allison Marie Asher

Student Theses and Dissertations

To better understand the migration and spatial patterns, population dynamics, population genetics, and paternity in Villosa iris, I conducted studies in the Spring (SR) and South Fork Spring (SFSR) rivers in 2006 and 2007. Population estimates were 166 ± 32 and 381 ± 37 individuals for SFSR1 and SR1, respectively. Home range and migration rates were small and male and female spatial patterns corresponded with spawning patterns, with more males found upstream of non-gravid females. Population genetic structuring was low between all populations (F_{st= 0.028), genetic diversity was lower in the SFSR (Fst= 0.012) than in …}

Molecular Phylogenetic, Morphometric, And Life History Analyses Of The Special Concern Freshwater Mussels: Obovaria Jacksoniana (Frierson, 1912) And Villosa Arkansasensis (Lea, 1862), Kentaro Inoue

Student Theses and Dissertations

The special concern Obovaria jacksoniana occurs from the Mississippi Interior Basin to Mobile River drainage. Villosa arkansasensis is often difficult to distinguish from O. jacksoniana based on conchological characters. Since both species have been ranked with conservation status, determining taxonomy and classification are important for conservation. The overall goal of my thesis was to better understand the taxonomic relationship between two species. Molecular phylogenetics, morphometrics, and life history analysis were three approaches used to provide a clearer picture of the genetic and taxonomical status of two species. Based on the findings of individual chapters, my overall conclusion is that O. …

Comparative Genomics And Molecular Evolution: New Genomic Resources For The Hymenoptera And Evolutionary Studies On The Genes Of The Nasonia Vitripennis Hox Complex., Monica Munoz-Torres

All Dissertations

Research on insects, the most successful group from all metazoans on earth, has important societal, as well as scientific benefits. Insects occupy a wide range of roles, which have an effect on human life either because the former pose serious threats to public health and commercial crops as well as in some cases represent the only way to propagate food resources. Despite their tremendous importance, insect genomics remained an uneven territory dominated by studies in the Drosophila group and the mosquitoes. This dissertation attempts to: 1) report on advances in the development and characterization of genomic tools for species of …

Application Of Microsatellite/Ssr Markers For The Identification Of Peach Rootstocks And Chromosomal Regions Associated With The Response To Peach Tree Short Life Syndrome, Xiaoyu Liu

All Dissertations

Peach Tree Short Life (PTSL) is a complicated disease syndrome involving nematodes, temperature, soil conditions, pruning and secondary pathogens. The disease occurs commonly in the southeastern U.S., and possibly in other areas of the U.S., Europe, South America and South Africa as the related Bacterial Canker Complex. PTSL causes premature tree death during the 3rd or 4th year after planting, resulting in large economic losses for growers. Recently, Guardian® &lsquo BY520-9&rsquo rootstock was selected for its tolerance to PTSL; however, the genetic basis for this tolerance remains unknown.
Nemaguard, a PTSL susceptible rootstock, and Guardian® selection 3-17-7 were crossed. Each …

Altered Regulation Of Aquaporin Gene Expression In Allergen And Il-13-Induced Mouse Models Of Asthma, Carissa M. Krane, Bijia Deng, Venkateshwar Mutyam, Casey A. Mcdonald, Stephen Pazdziorko, Lawrence Mason, Samuel Goldman, Marion Kasaian, Divya Chaudhary, Cara Williams, Melisa W.Y. Ho

Biology Faculty Publications

IL-13 is known to affect many processes that contribute to an asthmatic phenotype, including inflammation, fibrosis, and mucus production. Members of the aquaporin (AQP) family of transmembrane water channels are targets of regulation in models of lung injury and inflammation. Therefore, we examined AQP mRNA and protein expression in allergen and IL-13-induced mouse models of asthma. Lungs from ovalbumin sensitized and ovalbumin challenged (OVA/OVA) and IL-13 treated mice showed airway thickening, increased mucus production, and pulmonary eosinophilia. Pulmonary function tests showed a significant increase in methacholine-induced airway hyperreactivity in OVA/OVA and IL-13-treated mice as compared with controls. Quantitative PCR analysis …

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma, Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Faculty, Staff and Student Publications

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Multifactor Dimensionality Reduction Analysis Identifies Specific Nucleotide Patterns Promoting Genetic Polymorphisms, Eric Arehart, Scott Gleim, Bill White, John Hwa, Jason H. Moore

Dartmouth Scholarship

The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs) constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation.

Fitting Ace Structural Equation Models To Case-Control Family Data, Kristin N. Javaras, James I. Hudson, Nan M. Laird

COBRA Preprint Series

Investigators interested in whether a disease aggregates in families often collect case-control family data, which consist of disease status and covariate information for families selected via case or control probands. Here, we focus on the use of case-control family data to investigate the relative contributions to the disease of additive genetic effects (A), shared family environment (C), and unique environment (E). To this end, we describe a ACE model for binary family data and then introduce an approach to fitting the model to case-control family data. The structural equation model, which has been described previously, combines a general-family extension of …

Constructing And Using Case Studies In Genetics To Engage Students In Active Learning, Sue Styer

Faculty Publications & Research

One of the national goals in science education is to teach science in a way that mirrors the process of science as inquiry, described by the National Science Education Standards (NSES) Science Teaching Standard B and Content Standard A (NRC, 1996). Inquiry-based learning, including the use of case studies, is one of several types of active learning that allows students to experience critical thinking skills inherent in the science process (Handelsman et al., 2007). Using case studies also develops skills in group learning and personalizes and humanizes science, making it more relevant to students (National Center for Case Study Teaching …

Wnt And Egf Pathways Act Together To Induce C. Elegans Male Hook Development, Hui Yu, Adeline Seah, Michael A. Herman, Edwin L. Ferguson, H. Robert Horvitz, Paul W. Sternberg

School of Biological Sciences: Faculty Publications

Comparative studies of vulva development between Caenorhabditis elegans and other nematode species have provided some insight into the evolution of patterning networks. However, molecular genetic details are available only in C. elegans and Pristionchus pacificus. To extend our knowledge on the evolution of patterning networks, we studied the C. elegans male hook competence group (HCG), an equivalence group that has similar developmental origins to the vulval precursor cells (VPCs), which generate the vulva in the hermaphrodite. Similar to VPC fate specification, each HCG cell adopts one of three fates (1°, 2°, 3°), and 2° HCG fate specification …

Efficient Gene Replacements In Toxoplasma Gondii Strains Deficient For Nonhomologous End Joining, Barbara A. Fox, Jessica G. Ristuccia, Jason P. Gigley, David J. Bzik

Dartmouth Scholarship

A high frequency of nonhomologous recombination has hampered gene targeting approaches in the model apicomplexan parasite Toxoplasma gondii. To address whether the nonhomologous end-joining (NHEJ) DNA repair pathway could be disrupted in this obligate intracellular parasite, putative KU proteins were identified and a predicted KU80 gene was deleted. The efficiency of gene targeting via double-crossover homologous recombination at several genetic loci was found to be greater than 97% of the total transformants in KU80 knockouts. Gene replacement efficiency was markedly increased (300- to 400-fold) in KU80 knockouts compared to wild-type strains. Target DNA flanks of only approximately 500 bp were …

Associaton Tests That Accommodate Genotyping Errors, Ingo Ruczinski, Qing Li, Benilton Carvalho, M. Daniele Fallin, Rafael A. Irizarry, Thomas A. Louis

Johns Hopkins University, Dept. of Biostatistics Working Papers

High-throughput SNP arrays provide estimates of genotypes for up to one million loci, often used in genome-wide association studies. While these estimates are typically very accurate, genotyping errors do occur, which can influence in particular the most extreme test statistics and p-values. Estimates for the genotype uncertainties are also available, although typically ignored. In this manuscript, we develop a framework to incorporate these genotype uncertainties in case-control studies for any genetic model. We verify that using the assumption of a “local alternative” in the score test is very reasonable for effect sizes typically seen in SNP association studies, and show …

Sparse Linear Discriminant Analysis For Simultaneous Testing For The Significance Of A Gene Set/Pathway And Gene Selection, Michael C. Wu, Lingson Zhang, Zhaoxi Wang, David C. Christiani, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Hidden Markov Random Field Model For Genome-Wide Association Studies, Hongzhe Li, Zhi Wei, J M. Maris

UPenn Biostatistics Working Papers

Genome-wide association studies (GWAS) are increasingly utilized for identifying novel susceptible genetic variants for complex traits, but there is little consensus on analysis methods for such data. Most commonly used methods include single SNP analysis or haplotype analysis with Bonferroni correction for multiple comparisons. Since the SNPs in typical GWAS are often in linkage disequilibrium (LD), at least locally, Bonferonni correction of multiple comparisons often leads to conservative error control and therefore lower statistical power. In this paper, we propose a hidden Markov random field model (HMRF) for GWAS analysis based on a weighted LD graph built from the prior …

Genetic And Environmental Contributions To Body Mass Index: Comparative Analysis Of Monozygotic Twins, Dizygotic Twins And Same-Age Unrelated Siblings, Nancy Segal, R. Feng, Shirley Mcguire, D. Allison, S. Miller

Psychology

Background—Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from …

Thirty-Seven Additional Microsatellite Loci In The Pacific Lion-Paw Scallop (Nodipecten Subnodosus) And Cross-Amplification In Other Pectinids, Jessica Lynn Petersen, Ana M. Ibarra, Bernie May

Department of Animal Science: Faculty Publications

We characterized 37 new microsatellite markers in the Pacific lion-paw scallop (Nodipecten subnodosus) and tested for cross-amplification in four other species. Genetic diversity was estimated using 24 individuals from the Lagoon Ojo de Liebre, B.C.S., Mexico. Allelic richness varied from 5 to 27 alleles per locus and the average expected heterozygosity was 0.76. Ten loci exhibited significant departure from Hardy–Weinberg equilibrium likely due to the presence of null alleles. Sixteen of these markers cross-amplified in closely related N. nodosus, while little or no amplification was observed in three Argopecten species.

Development Of Pcr Assays To Detect And Characterise Salmonella Isolates From Cheese And Meat Products By Utilizing An Integrated Genomics Approach, Noelle Geraldine Mccarthy

Theses

Salmonella is an extremely important foodborne pathogen which is responsible for millions of cases of gastroenteritis annually. Salmonella outbreaks have been associated with numerous common food stuffs such as meat, dairy and seafood. Traditional culture based methods for the detection Salmonella are labourious and costly. Rapid detection and serovar identification would dramatically decrease the time required to identify Salmonella outbreaks and potential health risks.

In the US 99% of all Salmonella infections are caused by members of Salmonella enterica subspecies 1. Serovars within subspecies 1 can vary due to host specificity and pathogenicity. DNA sequencing projects have provided valuable genomic …

Proactive Procreation : Ethical Implications Of New Genetic Technologies For Parental Obligations To Future Offspring, L Syd M. Johnson

Legacy Theses & Dissertations (2009 - 2024)

This dissertation examines the ethical implications of recent genetic innovations, particularly preimplantation genetic diagnosis, for the obligations and duties of parents to future children. I critique common but uncompelling objections to the use of genetic information, diagnosis, and technology to influence the characteristics of future offspring, and conclude that genetic selection and enhancement are not different in kind or degree from other means of selection, direction, and enhancement that parents engage in to shape the lives of their children. Procreation is morally risky -- it risks imposing substantial burdens on persons who would not otherwise have to bear those burdens, …

Role Of Cyp2a5 In Drug Metabolism, Chemical Toxicity, And Maintenance Of Steroid Hormone Homeostasis : Insights From Studies On A Novel Cyp2a5-Null Mouse Model, Xin Zhou

Legacy Theses & Dissertations (2009 - 2024)

The central hypothesis is that CYP2A5 plays an important role in the metabolism of xenobiotic substrates, and in the toxicity induced by over-exposure to drugs, as well as in the metabolism of endogenous compounds and regulation of steroid hormone homeostasis. The specific aims are: 1) to generate and characterize a Cyp2a5-null mouse; 2) to determine the role of CYP2A5 in the systemic clearance of nicotine and cotinine; and 3) to explore the mechanisms underlying the resistance of the lateral nasal gland (LNG) of male Cyp2g1-null/Cyp2a5-low mouse and Cyp2a5-null mouse to acetaminophen (AP) toxicity.

An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert

Legacy Theses & Dissertations (2009 - 2024)

The receptor protein tyrosine kinases (RPTKs) and the non- receptor protein tyrosine kinases (PTKs) are among the most commonly up-regulated genes found in all types of cancers. Although, a large body of data implicates a majority of tyrosine kinases (TKs) in cancer, few have been extensively evaluated for any potential therapeutic benefit in any of the many subtypes of breast cancer. We have used RNA interference (RNAi) to perform a large-scale loss-of-function analysis to facilitate the identification of individual factors necessary for the survival of an ErbB2 positive breast cancer cell line. We have found that 30% of the TKs …

Estrogenic Compounds Downstream From Three Small Cities In Eastern Nebraska: Occurrence And Biological Effect, Marlo K. Sellin, Daniel D. Snow, Debbie L. Akerly, Alan S. Kolok

Biology Faculty Publications

Recent studies have detected estrogenic compounds in surface waters in North America and Europe. Furthermore, the presence of estrogenic compounds in surface waters has been attributed, in some cases, to the discharge of wastewater treatment plant (WWTP) effluent. The primary objective of the current study was to determine if WWTP effluent contributes estrogens to the surface waters of Nebraska. A second objective of this study was to determine if estrogens were found in concentrations sufficient enough to manifest feminizing effects on fish. These objectives were satisfied by deploying polar organic chemical integrative samplers (POCIS) and caged fathead minnows at eight …