Genetics Commons^™

Gene Ontology Analysis Of Pairwise Genetic Associations In Two Genome-Wide Studies Of Sporadic Als, Nora Chung Kim, Peter C. Andrews, Folkert W. Asselbergs, H Robert Frost, Scott M. Williams, Brent T. Harris, Cynthia Read, Kathleen D. Askland, Jason H. Moore

Dartmouth Scholarship

It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO).

Politicizing Patents - Patenting Biotechnology In The Wake Of Section 33, Prometheus, And Cls Bank, Jonathan R. K. Stroud

Celebrating WCL Student Authors

Tucked into the America Invents Act is the first statutory exemption for any patentable subject matter. Section 33 renders unpatentable all claims “encompassing a human being.” By recognizing a vague subject matter – exception for human beings despite the fact that internal policies had long militated against such patent claims, Congress has politicized the patent law to an unheard-of degree. While textually consistent with internal USPTO policy, the passage of § 33 should not be seen as an invitation to litigators to expand § 101 unpatentable-subject-matter challenges to validity by including arguments that medical methods, genetic tests, biological chimeras, or …

Characterization Of The Infectivity Of Non-Replicating Human Immunodeficiency Virus (Hiv)-Derived Viral Vectors., Vanessa E. Rodriguez, Manuel Llano, Luis Valdes

COURI Symposium Abstracts, Summer 2012

The ability of HIV-derived viral vectors to integrate genes of interest into the host genome causing permanent phenotypic modifications makes them excellent tools in gene therapy. However, integration also causes insertional mutagenesis and controlling integration site selection will increase the biosafety of these molecular tools. HIV DNA integration site selection is influenced by LEDGF/p75, a chromatin-bound cellular protein that interacts with the viral enzyme integrase through the integrase binding domain (IBD). Integrase catalyzes viral DNA integration and non-covalently associates with the HIV genome forming the pre-integration complex (PIC). Therefore, interaction of chromatin-bound LEDGF/p75 with the PIC-associated integrase tethers the HIV …

Selfish Little Circles: Transmission Bias And Evolution Of Large Deletion-Bearing Mitochondrial Dna In Caenorhabditis Briggsae Nematodes, Katie A. Clark, Dana K. Howe, Kristin Gafner, Danika Kusuma, Sita Ping, Suzanne Estes

Biology Faculty Publications and Presentations

Selfish DNA poses a significant challenge to genome stability and organismal fitness in diverse eukaryotic lineages. Although selfish mitochondrial DNA (mtDNA) has known associations with cytoplasmic male sterility in numerous gynodioecious plant species and is manifested as petite mutants in experimental yeast lab populations, examples of selfish mtDNA in animals are less common. We analyzed the inheritance and evolution of mitochondrial DNA bearing large heteroplasmic deletions including nad5 gene sequences (nad5Δ mtDNA), in the nematode Caenorhabditis briggsae. The deletion is widespread in C. briggsae natural populations and is associated with deleterious organismal effects. We studied the inheritance patterns of nad5Δ …

The Effects Of Cytokinin On The Transcriptional Regulation Of Pin Expression In Arabidopsis Thaliana, Elizabeth Burgess

Honors Theses and Capstones

The processes of cell division and differentiation are critical to the development of any multicellular organism. During the formation of plant roots these processes take place at a region of the root tip called the meristem. Cytokinin and auxin are two plant growth hormones that influence this process. Although these two growth hormones are both necessary they also appear in many ways to have an antagonistic relationship. As meristematic root cells undergo differentiation they cease dividing. It has been proposed that the size of the root meristem and thus the overall rate of root growth are determined by the balance …

Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen

Dartmouth Scholarship

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …

Genetic Comparison Of Water Molds From Embryos Of Amphibians Rana Cascadae, Bufo Boreas And Pseudacris Regilla, Kori K. Ault, James E. Johnson, Holly C. Pinkart, R. Steven Wagner

All Faculty Scholarship for the College of the Sciences

Water molds that cause the disease saprolegniasis have been implicated in widespread mortality of amphibian embryos. However, because of the limitations of traditional identification methods, water mold species involved in die-offs or utilized in ecological studies often remain unidentified or identified only as Saprolegnia ferax. Furthermore, water mold taxonomy requires revision, so very distinct organisms may all be called S. ferax. Recent DNA-based studies indicate that the diversity of water molds infecting amphibian embryos is significantly higher than what was previously known, but these studies rely on culture methods, which may be biased towards taxa that grow best …

Computational Design And Characterization Of A Temperature-Sensitive Plasmid Replicon For Gram Positive Thermophiles, Daniel G. Olson, Lee R. Lynd

Dartmouth Scholarship

Temperature-sensitive (Ts) plasmids are useful tools for genetic engineering, but there are currently none compatible with the gram positive, thermophilic, obligate anaerobe, Clostridium thermocellum. Traditional mutagenesis techniques yield Ts mutants at a low frequency, and therefore requires the development of high-throughput screening protocols, which are also not available for this organism. Recently there has been progress in the development of computer algorithms which can predict Ts mutations. Most plasmids currently used for genetic modification of C. thermocellum are based on the replicon of plasmid pNW33N, which replicates using the RepB replication protein. To address this problem, we set out …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Why Odds Ratio Estimates Of Gwas Are Almost Always Close To 1.0, Yutaka Yasui

COBRA Preprint Series

“Missing heritability” in genome-wide association studies (GWAS) refers to the seeming inability for GWAS data to capture the great majority of genetic causes of a disease in comparison to the known degree of heritability for the disease, in spite of GWAS’ genome-wide measures of genetic variations. This paper presents a simple mathematical explanation for this phenomenon, assuming that the heritability information exists in GWAS data. Specifically, it focuses on the fact that the great majority of association measures (in the form of odds ratios) from GWAS are consistently close to the value that indicates no association, explains why this occurs, …

The Tlo Proteins Are Stoichiometric Components Of Candida Albicans Mediator Anchored Via The Med3 Subunit, Anda Zhang, Kostadin O. Petrov, Emily R. Hyun, Zhongle Liu, Scott A. Gerber, Lawrence C. Myers

Dartmouth Scholarship

The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo …

Mutation And Complementation Of A Cellulose Synthase (Cesa) Gene, Ahmed Y. El-Araby

Senior Honors Projects

Cellulose is a carbohydrate polymer that is composed of repeating glucose subunits. Being the most abundant organic compound in the biosphere and comprising a large percentage of all plant biomass, cellulose is extremely plentiful and has a significant role in nature. Cellulose is present in plant cell walls, in commercial products such as those made from wood or cotton, and is of interest to the biofuel industry as a potential alternative fuel source. Although indigestible by humans, cellulose is nutritionally valuable, serving as a dietary fiber. Because of its ubiquity and importance in many areas, studying cellulose will prove to …

Signaling Pathways And Genetic Interactions That Lead To Metastatic Cancer In Drosophila Melanogaster, Amanda Cole

Renée Crown University Honors Thesis Projects - All

Cancer is a complex and multigenic disease, which is typically initiated by genetic mutations in tumor suppressor genes that regulate homeostatic mechanisms within cells. Oncogenic promoter mutations, like those involved in signal transduction pathways, also have the potential to induce cancer in an otherwise healthy organism. Transformation is highly dependent upon mutations to both tumor suppressor and oncogenes, as neither mutation is exclusive in its ability to generate malignant tumors. In the model organism, Drosophila melanogaster, I have generated metastatic cancer through the genetic effect of overactive Raf signaling, in conjugation with silencing selected tumor suppressor genes using RNA …

Fluorescence-Based Reporter For Gauging Cyclic Di-Gmp Levels In Pseudomonas Aeruginosa, Morten T. Rybtke, Bradley R. Borlee, Keiji Murakami, Yasuhiko Irie, Morten Hentzer, Thomas E. Nielsen, Michael Givskov, Matthew R. Parsek, Tim Tolker-Nielsen

Biology Faculty Publications

The increased tolerance toward the host immune system and antibiotics displayed by biofilm-forming Pseudomonas aeruginosa and other bacteria in chronic infections such as cystic fibrosis bronchopneumonia is of major concern. Targeting of biofilm formation is believed to be a key aspect in the development of novel antipathogenic drugs that can augment the effect of classic antibiotics by decreasing antimicrobial tolerance. The second messenger cyclic di-GMP is a positive regulator of biofilm formation, and cyclic di-GMP signaling is now regarded as a potential target for the development of antipathogenic compounds. Here we describe the development of fluorescent monitors that can gauge …

Knowledge, Attitudes, And Utilization Of Brca Testing Among Obstetricians And Gynecologists, Salma Nassef

Dissertations and Theses (Open Access)

Hereditary breast and ovarian cancer (HBOC) is an inherited cancer syndrome that is associated with mutations in the BRCA1 and BRCA2 genes. Carriers of BRCA mutations, both men and women, are at an increased risk for developing certain cancers. Carriers are most notably at an increased risk to develop breast and ovarian cancers; however an increased risk for prostate cancer, melanoma, and pancreatic cancers has also been associated with these mutations. In 2009 the American Congress of Obstetricians and Gynecologists (ACOG) released a practice bulletin stating that evaluating a patient’s risk for HBOC should be a routine part of obstetric …

Genetic Variation In Field And Laboratory Populations Of The Spined Soldier Bug, Podisus Maculiventris, Kathleen Kneeland, Thomas A. Coudron, Erica Lindroth, David Stanley, John E. Foster

Department of Entomology: Faculty Publications

The predatory spined soldier bug, Podisus maculiventris (Say) (Heteroptera: Pentatomidae), is an economically important and highly valued biological control agent. There is substantial information on the biology, ecology, behavior, and rearing of this stink bug. However, virtually nothing is known of its genetic variation, in natural or domesticated populations. To address this lacuna, we used amplified fragment length polymorphism (AFLP) to assess the genetic variability of field and laboratory populations. Four AFLP universal primer combinations yielded a total of 209 usable loci. The AFLP results showed greater genetic variability between populations from Missouri and Mississippi (both USA), and relatively low …

Abd-A Regulation By The Iab-8 Noncoding Rna, Maheshwar Gummalla, Robert K. Maeda, Javier J. Castro Alvarez, Henrik Gyurkovics, Kevin A. Edwards, Swetha Singari, Welcome Bender

Faculty Publications – Biological Sciences

The homeotic genes in Drosophila melanogaster are aligned on the chromosome in the order of the body segments that they affect. The genes affecting the more posterior segments repress the more anterior genes. This posterior dominance rule must be qualified in the case of abdominal-A (abd-A) repression by Abdominal-B (Abd-B). Animals lacking Abd-B show ectopic expression of abd-A in the epidermis of the eighth abdominal segment, but not in the central nervous system. Repression in these neuronal cells is accomplished by a 92 kb noncoding RNA. This "iab-8 RNA" produces a micro RNA to repress abd-A, but also has a …

Genetic Predictors Of Hyperglycemia Due To Hydrochlorothiazide Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Response to pharmacological treatment is variable among individuals. Some patients respond favorably to a drug while others develop adverse reactions. Early investigations showed evidence of variation in genes that code for drug receptors, drug transporters, and drug metabolizing enzymes; and pharmacogenetics appeared as the science that studies the relationship between drug response and genetic variation.

Thiazide diuretics are the recommended first-line monotherapy for hypertension (i.e. SBP>140 or DBP>90). Even so, diuretics are associated with adverse metabolic side effects, such as hyperglycemia, which increase the risk of developing type 2 diabetes. Published approaches testing variation in candidate genes (e.g. …

Effects Of Thymus Size And Involution On The Contribution Of Recent Thymic Emigrants To The Peripheral T Cell Pool, Michelle L. Bolner

Dissertations and Theses (Open Access)

The contribution of recent thymic emigrants (RTEs) to the peripheral naïve T cell population is necessary to maintain diversity of the T cell receptor (TCR) repertoire and produce immune responses against newly encountered antigens.

The thymus involutes with age, after irradiation or chemotherapy, and due to severe viral infections. Thymus involution results in decreased thymopoiesis and RTE output leading to a reduced diversity of peripheral T cells. This increases susceptibility to disease and impairs immune responsiveness to vaccines. Therefore, studies aimed at maintaining or regenerating thymic function are integral for maintaining and restoring peripheral TCR diversity.

Mice that express a …

Predictors Of Contralateral Breast Cancer In Brca Negative Women, Ann E. Simmons

Dissertations and Theses (Open Access)

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk …

Diversity, Identification, Mapping And Pyramiding Of Genes For Resistance To Soybean Mosaic Virus [Glycine Max (L.) Merr.], Innan Gloria Cervantes Martinez

Graduate Theses and Dissertations

Soybean Mosaic Virus (SMV) is a prevalent viral pathogen transmitted by aphids and via seed, causing significant yield loss and quality reduction. There are seven SMV strain groups (G1 to G7) and three resistance loci( Rsv1, Rsv3, and Rsv4) reported in soybean. New sources of SMV resistance would be valuable for breeding cultivars with durable resistance to multiple strains. The objectives of this research were to analyze genetic diversity of SMV-resistant soybean germplasm at the molecular level; to pyramid three genes from different sources for durable SMV resistance; and to identify and map new genes/alleles for differential reactions to SMV …

Heterotopic Ossification: Cellular Basis, Symptoms, And Treatment, Brian Wolfe

Senior Honors Theses

Heterotopic ossification (HO) is the process by which calcified bone develops in soft tissues. Because of the abnormal calcification, complications such as bone deformation, loss of range of motion, and joint immobility adversely affect patients. There are many genetic types of heterotopic ossification, namely fibrodysplasia ossificans progressiva, progressive osseous heteroplasia, and Albright hereditary osteodystrophy. However, this condition can also arise from surgery, burns, or traumatic injuries, so it is seen as an important area for research in the future. There are various treatments available such as non-steroidal anti-inflammatory drugs and radiation therapy, as well as combinations of the two. The …

Revised Selection Criteria For Candidate Restriction Enzymes In Genome Walking, Ali Taheri, Stephen J. Robinson, Isobel Parkin, Margaret Y. Gruber

Agricultural and Environmental Sciences Faculty Research

A new method to improve the efficiency of flanking sequence identification by genome walking was developed based on an expanded, sequential list of criteria for selecting candidate enzymes, plus several other optimization steps. These criteria include: step (1) initially choosing the most appropriate restriction enzyme according to the average fragment size produced by each enzyme determined using in silico digestion of genomic DNA, step (2) evaluating the in silico frequency of fragment size distribution between individual chromosomes, step (3) selecting those enzymes that generate fragments with the majority between 100 bp and 3,000 bp, step (4) weighing the advantages and …

Widespread Diversity In African Toads (Anura: Amietophrynus), Nancy P. Conkey ^, Eli Greenbaum *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

How Roads Affect The Population Genetic Structure Of The Lizard Uta Stansburiana In The Northern Chihuahuan Desert, Priscilla D. Duran ^, Kevin W. Floyd, Elizabeth J. Walsh *

COURI Symposium Abstracts, Spring 2012

Urbanization can have significant ecological effects on natural populations, including habitat fragmentation through increased road density. Roads may isolate populations, causing disruption of gene flow, inbreeding, and decreased genetic diversity. In this study we investigate how two roads, interstate highway I-10 and rural country road NM-9, affect population genetic structure of ideblotched lizards (Uta stansburiana) in the northern Chihuahuan Desert of New Mexico. Lizards were trapped on both sides of each road, plus one control site/road. Nine microsatellite loci were amplified to determine signatures of disrupted gene flow. Genotypes were obtained for 144 individuals from three sites, I-10 …

Resource Availability, Mortality And Fertility: A Path Analytic Approach To Global Life History Variation, Mark A. Caudell, Robert J. Quinlan

Human Biology Open Access Pre-Prints

Humans exhibit considerable diversity in timing and rate of reproduction. Life history theory suggests that ecological cues of resource richness and survival probabilities shape human phenotypes across populations. Populations experiencing high extrinsic mortality due to uncertainty in resources should exhibit faster life histories. Here we use a path analytic approach informed by life history theory to model the multiple pathways between resources, mortality rates, and reproductive behavior in 191 countries. Resources that account for the most variance in population mortality rates are predicted to explain the most variance in total fertility rates. Results indicate that resources (e.g., calories, sanitation, education, …

The Family Name As Socio-Cultural Feature And Genetic Metaphor: From Concepts To Methods, Pierre Darlu, Gerrit Bloothooft, Alessio Boattini, Leendert Brouwer, Matthijs Brouwer, Guy Brunet, Pascal Chareille, James Cheshire, Richard Coates, Paul Longley, Kathrin DräGer, Bertrand Desjardins, Patrick Hanks, Kees Mandemakers, Pablo Mateos, Davide Pettener, Antonella Useli, Franz Manni

Human Biology Open Access Pre-Prints

A recent workshop on "Family name between socio-cultural feature and genetic metaphor - From concepts to methods" was held in Paris on the 9th and 10th December 2010, partly sponsored by the Social Science and Humanity Institute (CNRS), and by Human Biology. This workshop was intended to facilitate exchanges on recent questions related to the names of persons and to confront different multidisciplinary approaches in a field of investigation where geneticists and historians, geographers, sociologists and ethnologists have all an active part. Here are the abstracts of some contributions.

Association Among Obesity-Related Anthropometric Phenotypes: Analyzing Genetic And Environmental Contribution, Aline Jelenkovic, Esther Rebato

Human Biology Open Access Pre-Prints

Obesity has become a public health and policy problem in many parts of the world. Epidemiological and population studies in this field are usually based on different anthropometric measures, however, common genetic and environmental factors between these phenotypes have been scarcely studied. The objective of this work is to assess the strength of these factors on the covariation among a large set of obesity-related traits. The subject group consisted of 533 nuclear families living in the Greater Bilbao (Spain), and included 1702 individuals aged 2-61 years. Detailed anthropometric measurements (stature, breadths, circumferences and skinfolds) were carried out in each subject. …

Studies On Enzyme Functional Evolution In The Sabath Multigene Family Using Phylogenetic And Biochemical Approaches, Ruiqi Huang

Masters Theses

Gene duplication is believed to be the major source for providing genetic materials for the innovation and diversification of protein functions; natural selection and/or neutral drift then works on these genetic materials to guide their evolutionary directions. Here, I used the salicylic acid/benzoic acid/theobromine (SABATH) multigene family to study how natural selection acted on duplicated genes to prompt functional diversification. Members in this family methylate plant secondary metabolites by transferring the methyl group from S-adenosyl-L-methionine (SAM) to the carboxyl group or ring nitrogen of the substrates. In the Apocynaceae and Solanaceae lineage of this family, I documented three putative gene …

Microgeographic Differentiation In Historical Yemen Inferred By Morphometric Distances, Maria Enrica Danubio, Emanuele Sanna, Fabrizio Rufo, Domenico Martorella, Elvira Vecchi, Alfredo Coppa

Human Biology Open Access Pre-Prints

This study analysed the variations in space of 8 body dimensions and 11 measures of the head of 1,244 adult Yemenite males, collected in 1933/34 by Coon in Yemen and in Hadhramawt. The aim was to evaluate the presence of geographic microdifferentiation of the populations settled in the different regions of Yemen at the time. Coon sub-divided the sample into 6 geographical areas according to birthplace and ethnicity of the individuals: Tihamah, the Western Mountains, the Central Plateau, the South Coast, the Eastern Mountains and Hadhramawt. The results of ANCOVA (age as covariate) show that the observed differences of all …