Genetics and Genomics Commons^™

Contribution Of The Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (Erpc) To Complement Resistance Of Borrelia Burgdorferi, Claudia Hammerschmidt, Teresia Hallström, Christine Skerka, Reinhard Wallich, Brian Stevenson, Peter F Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated …

"Release Factor 2 (Rf2) Is A Key Structural Component Found In The Ribosomes Of All Prokaryotic Organisms…", Zachary Wise

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

No abstract provided.

The Role Of Chromatin And Cofactors In The Transcriptional Memory Effect Exerted In Saccharomyces Cerevisiae, Emily Leigh Paul

Legacy Theses & Dissertations (2009 - 2024)

Abf1 and Rap1 are functionally similar general regulatory factors (GRFs) found in Saccharomyces cerevisiae . Abf1, in its role as a transcriptional activator, exerts a memory effect on some genes under its control. This effect results in transcription levels remaining steady when Abf1 dissociates from its binding site in a conditional mutant. In contrast, Rap1 fails to elicit the same effect on its regulatory targets. Transcriptional memory effects have been observed in many fields of study, including immunology, cancer, and stem cells, and conservation of transcription machinery will allow studies in yeast to be applied to higher organisms.

The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake

Legacy Theses & Dissertations (2009 - 2024)

Candida albicans is a fungal pathogen that causes serious infections among immune-compromised patients and premature infants. C. albicans can become drug resistant, therefore, identifying new antifungal drug targets is an important goal. Here, we study a peptidyl-prolyl cis/trans isomerase called Ess1 as a potential drug target. Ess1 is conserved among pathogenic fungi, and therefore, potential inhibitors of Ess1 should display a broad spectrum of activity. We confirm that Ess1 is essential for growth in Candida albicans, but unlike the previously published find, deleting one copy of the C. albicans ESS1 gene did not affect morphogenetic switching. However, further reducing activity …

An Unbiased Approach To Identify Genes Involved In Development In A Turtle With Temperature-Dependent Sex Determination, Jena L. Chojnowski, Edward L. Braun

Natural Sciences Faculty Publications

Many reptiles exhibit temperature-dependent sex determination (TSD). The initial cue in TSD is incubation temperature, unlike genotypic sex determination (GSD) where it is determined by the presence of specific alleles (or genetic loci). We used patterns of gene expression to identify candidates for genes with a role in TSD and other developmental processes without making a priori assumptions about the identity of these genes (ortholog-based approach). We identified genes with sexually dimorphic mRNA accumulation during the temperature sensitive period of development in the Red-eared slider turtle (Trachemys scripta), a turtle with TSD. Genes with differential mRNA accumulation in response to …

Consuming Direct-To-Consumer Genetic Tests: The Role Of Genetic Literacy And Knowledge Calibration, Yvette E. Pearson, Yuping Liu-Thompkins

Philosophy Faculty Publications

As direct-to-consumer marketing of medical genetic tests grows in popularity, there is an increasing need to better understand the ethical and public policy implications of such products. The complexity of genetic tests raises serious concerns about whether consumers possess the knowledge to make sound decisions about their use. This research examines the effects of educational intervention and feedback on consumers' genetic literacy and calibration -- the gap between consumers' actual knowledge and how much they think they know. The authors find that consumers' genetic knowledge was generally low and that people tended to underestimate their knowledge level. Furthermore, consumers' perceived …

Dynamics Of Envelope Evolution In Clade C Shiv-Infected Pig-Tailed Macaques During Disease Progression Analyzed By Ultra-Deep Pyrosequencing, For Yue Tso, Damien C. Tully, Sandra Gonzalez, Christopher Quince, On Ho, Patricia Polacino, Ruth M. Ruprecht, Shiu-Lok Hu, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of nonhuman primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a nonprogressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep …

Mechanistic Studies Of A Novel Ppar-Gamma Mutant That Causes Lipodystrophy And Diabetes, Olga Astapova

Wayne State University Dissertations

PPAR-gamma is a nuclear receptor that plays a central role in metabolic regulation by regulating extensive gene expression networks in adipose, liver, skeletal muscle and many other tissues. Human PPAR-gamma mutations are rare and cause a monogenetic form of severe type II diabetes with metabolic syndrome, known as familiar partial lypodystrophy. The E157D PPAR-gamma mutant causes atypical lipodystrophy in a large Canadian kindred, presenting with multiple musculoskeletal, neurological and hematological abnormalities in addition to the classic lipodystrophy features of insulin-resistant diabetes, hypertension and dyslipidemia. This mutation is localized to the p-box of PPAR-gamma, a small region that interacts directly with …

Genetics And Cancer, Sachin Puri

A with Honors Projects

Genes' effect in body and relationship with cancer. Role in cell cycle and angiogenesis.

Cryptic Distant Relatives Are Common In Both Isolated And Cosmopolitan Genetic Samples, Brenna M. Henn, Lawrence S. Hon, J. Michael Macpherson, Nicholas Eriksson, Serge Saxonov, Itsik Pe'er, Joanna Mountain

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2nd to 9th cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100–300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD) in a subset of individuals from the 23andMe customer database (n = 22,757) and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952). With data from 121 populations, we show that the average amount …

Effects Of Reactive Oxygen Species On Life History Traits Of Caenorhabditis Elegans, Samson William Smith

Dissertations and Theses

Evolutionary life history theory predicts that tradeoffs among fitness-related phenotypes will occur as a result of resource limitations and/or physiological constraints. Such tradeoffs are defined as the cost(s) incurred on one component of fitness (e.g., reproduction) by the increased expression of another fitness-related trait (e.g., longevity). Only recently have researchers begun to investigate the mechanistic bases of life history tradeoffs. A recent proposal is that reactive oxygen species (ROS) have a central role in shaping life history traits and tradeoffs. Research on disparate animal taxa has highlighted strong correlations between oxidative stress resistance and fitness-related life history traits, for example. …

Causes And Consequences Of Mitochondrial Variation In Caenorhabditid Nematodes, Kiley Ann Hicks

Dissertations and Theses

Mitochondria are dynamic organelles that harbor their own stream-lined genome and generate much of the ATP necessary to sustain eukaryotic life via an electron transport chain (ETC). Because of the central role for mitochondria in organismal physiology, mitochondrial genetic and phenotypic variation can alter organismal fitness and affect population genetic and evolutionary outcomes. Despite the far-reaching relevance of mitochondria to evolutionary processes and human health, we lack a basic understanding of the causes and consequences of mitochondrial genetic and phenotypic variation. In this thesis, I quantified mitochondrial reactive oxygen species (ROS), membrane potential (δΨM), and mitochondrial morphological traits within Caenorhabditis …

Complete Genome Sequence Of Clostridium Clariflavum Dsm 19732, Javier A. Izquierdo, Lynne Goodwin, Karen W. Davenport, Hazuki Teshima

Dartmouth Scholarship

Clostridium clariflavum is a Cluster III Clostridium within the family Clostridiaceae isolated from thermophilic anaerobic sludge (Shiratori et al, 2009). This species is of interest because of its similarity to the model cellulolytic organism Clostridium thermocellum and for the ability of environmental isolates to break down cellulose and hemicellulose. Here we describe features of the 4,897,678 bp long genome and its annotation, consisting of 4,131 protein-coding and 98 RNA genes, for the type strain DSM 19732.

Protein Structure Networks, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

The application of the field of network science to the scientific disciplines of structural biology and biochemistry, have yielded important new insights into the nature and determinants of protein structures, function, dynamics and the folding process. Advancements in further understanding protein relationships through network science have also reshaped the way we view the connectivity of proteins in the protein universe. The canonical hierarchical classification can now be visualized for example, as a protein fold continuum. This review will survey several key advances in the expanding area of research being conducted to study protein structures and folding using network approaches.

Expansion Dating: Calibrating Molecular Clocks In Marine Species From Expansions Onto The Sunda Shelf Following The Last Glacial Maximum, Eric D. Crandall, Elizabeth J. Sbrocco, Timery S. Deboer, Paul H. Barber, Kent E. Carpenter

Biological Sciences Faculty Publications

The rate of change in DNA is an important parameter for understanding molecular evolution and hence for inferences drawn from studies of phylogeography and phylogenetics. Most rate calibrations for mitochondrial coding regions in marine species have been made from divergence dating for fossils and vicariant events older than 1-2 My and are typically 0.5-2% per lineage per million years. Recently, calibrations made with ancient DNA (aDNA) from younger dates have yielded faster rates, suggesting that estimates of the molecular rate of change depend on the time of calibration, decaying from the instantaneous mutation rate to the phylogenetic substitution rate. aDNA …

Higher Il-6 And Il6:Igf Ratio In Patients With Barth Syndrome, Lori D. Wilson, Sadeeka Al-Majid, Cyril Rakovski, Christina D. Schwindt

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5). The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients.

Methods: Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs) and 14 healthy control males (8 - 21 yrs) was …

Advancing Our Understanding Of The Inheritance And Transmission Of Pectus Excavatum, Lisa Horth, Michael W. Stacey, Virginia K. Proud, Kara Segna, Chelsea Rutherford, Donald Nuss, Robert E. Kelly

Bioelectrics Publications

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum …

Development And Validation Of A Novel Reporter Assay For Human Papillomavirus Type 16 Late Gene Expression, Beatrice Orru, Ciaran Cunniffe, Fergus Ryan, Stefan Schwartz

Articles

To facilitate the investigations of HPV-16 late gene expression HPV-16 reporter plasmids were generated using previously described sub-genomic HPV-16 plasmids, named pBEL and pBELM, that, similar to the full viral genome, produce primarily HPV-16 early mRNAs and very little, if any, late mRNAs in cervical cancer cells. The HPV-16 late L1 gene was replaced by the chloramphenicol acetyltransferase (CAT) reporter gene, or green fluorescent protein (GFP), preceded by the poliovirus internal ribosome entry site (IRES). Results show that the reporter genes mimic the expression of L1 from these plasmids. For example, overexpression of adenovirus E4orf4 protein (E4orf4), polypyrimidine tract binding …

Following The Trail Of Ants: An Examination Of The Work Of E.O. Wilson, Samantha Kee

Writing Across the Curriculum

No abstract provided.

Successful Genotyping Of Microsatellites In The Woolly Mammoth, Yasuko Ishida, Alfred L. Roca, Stephen Fratpietro, Alex D. Greenwood

Biological Sciences Faculty Publications

Genetic analyses using ancient DNA from Pleistocene and early Holocene fossils have largely relied on mitochondrial DNA (mtDNA) sequences. Among woolly mammoths, Mammuthus primigenius, mtDNA analyses have identified 2 distinct clades (I and II) that diverged 1-2 Ma. Here, we establish that microsatellite markers can be effective on Pleistocene samples, successfully genotyping woolly mammoth specimens at 2 loci. Although significant differentiation at the 2 microsatellite loci was not detected between 16 clade I and 4 clade II woolly mammoths, our results demonstrate that the nuclear population structure of Pleistocene species can be examined using fast-evolving nuclear microsatellite markers.

Genome Sequence Of Strain Himb624, A Cultured Representative From The Om43 Clade Of Marine Betaproteobacteria, Megan Huggett, Darren Hayakawa, Michael Rappe

Research outputs 2012

Strain HIMB624 is a planktonic marine bacterium within the family Methylophilaceae of the class Betaproteobacteria isolated from coastal seawater of Oahu, Hawaii. This strain is of interest because it is one of few known isolates from an abundant clade of Betaproteobacteria found in cultivation-independent studies of coastal seawater and freshwater environments around the globe, known as OM43. Here we describe some preliminary features of the organism, draft genome sequence and annotation, and comparative genomic analysis with one other sequenced member of this clade (strain HTCC2181). The 1,333,209 bp genome of strain HIMB624 is arranged in a single scaffold containing four …

Functional Promiscuity Of The Cog0720 Family, Gabriela Phillips, Laura L. Grochowski, Shilah Bonnett, Huimin Xu, Marc Bailly, Crysten Haas-Blaby, Basma El Yacoubi, Dirk Iwata-Reuyl, Robert H. White, Valérie De Crécy-Lagard

Chemistry Faculty Publications and Presentations

The biosynthesis of GTP derived metabolites such as tetrahydrofolate (THF), biopterin (BH4), and the modified tRNA nucleosides queuosine (Q) and archaeosine (G⁺) relies on several enzymes of the Tunnel-fold superfamily. A subset of these proteins include the 6-pyruvoyl-tetrahydropterin (PTPS-II), PTPS-III, and PTPS-I homologs, all members of the COG0720 family, that have been previously shown to transform 7,8-dihydroneopterin triphosphate (H₂NTP) into different products. PTPS-II catalyzes the formation of 6-pyruvoyltetrahydropterin in the BH₄ pathway. PTPS-III catalyzes the formation of 6-hydroxylmethyl-7,8-dihydropterin in the THF pathway. PTPS-I catalyzes the formation of 6-carboxy-5,6,7,8-tetrahydropterin in the Q pathway. Genes of these …

Subspecific Status Of The Korean Tiger Inferred By Ancient Dna Analysis, Mu-Yeong Lee, Jee Yun Hyun, Seo-Jin Lee, Junghwa An, Eunok Lee, Mi-Sook Min, Junpei Kimura, Shin-Ichirio Kawada, Nozomi Kurihara, Shu-Jin Luo, Stephen J. O'Brien, Warren E. Johnson, Hang Lee

Biology Faculty Articles

The tiger population that once inhabited the Korean peninsula was initially considered a unique subspecies (Panthera tigris coreensis), distinct from the Amur tiger of the Russian Far East (P. t. altaica). However, in the following decades, the population of P. t. coreensis was classified as P. t. altaica and hence forth the two populations have been considered the same subspecies. From an ecological point of view, the classification of the Korean tiger population as P. t. altaica is a plausible conclusion. Historically, there were no major dispersal barriers between the Korean peninsula and the habitat of …

Tissue Sampling Methods And Standards For Vertebrate Genomics, Pamela B. Y. Wong, Edward O. Wiley, Warren E. Johnson, Oliver A. Ryder, Stephen J. O'Brien, David Haussler, Klaus-Peter Koepfli, Marlys L. Houck, Polina L. Perelman, Gabriela Mastromonaco, Andrew C. Bentley, Byrappa Venkatesh, Ya-Ping Zhang, Robert W. Murphy, Genome 10k Project Community Of Scientists

Biology Faculty Articles

The recent rise in speed and efficiency of new sequencing technologies have facilitated high-throughput sequencing, assembly and analyses of genomes, advancing ongoing efforts to analyze genetic sequences across major vertebrate groups. Standardized procedures in acquiring high quality DNA and RNA and establishing cell lines from target species will facilitate these initiatives. We provide a legal and methodological guide according to four standards of acquiring and storing tissue for the Genome 10K Project and similar initiatives as follows: four-star (banked tissue/cell cultures, RNA from multiple types of tissue for transcriptomes, and sufficient flash-frozen tissue for 1 mg of DNA, all from …

Mutation At The Human D1s80 Minisatellite Locus, Kuppareddi Balamurugan, Martin L. Tracey, Uwe Heine, George C. Maha, George Duncan

Biology Faculty Articles

Little is known about the general biology of minisatellites. The purpose of this study is to examine repeat mutations from the D1S80 minisatellite locus by sequence analysis to elucidate the mutational process at this locus. This is a highly polymorphic minisatellite locus, located in the subtelomeric region of chromosome 1. We have analyzed 90,000 human germline transmission events and found seven (7) mutations at this locus. The D1S80 alleles of the parentage trio, the child, mother, and the alleged father were sequenced and the origin of the mutation was determined. Using American Association of Blood Banks (AABB) guidelines, we found …

Genome Empowerment For The Puerto Rican Parrot – Amazona Vittata, Stephen J. O'Brien

Biology Faculty Articles

A unique community-funded project in Puerto Rico has launched whole-genome sequencing of the critically endangered Puerto Rican Parrot (Amazona vittata), with interpretation by genome bioinformaticians and students, and deposition into public online databases. This is the first article that focuses on the whole genome of a parrot species, one endemic to the USA and recently threatened with extinction. It provides invaluable conservation tools and a vivid example of hopeful prospects for future genome assessment of so many new species. It also demonstrates inventive ways for smaller institutions to contribute to a field largely considered the domain of large …

Genetic Control Of A Central Pattern Generator: Rhythmic Oromotor Movement In Mice Is Controlled By A Major Locus Near Atp1a2, Steven J. St. John, John D. Boughter Jr, Megan K. Mulligan, Kenichi Tokita, Lu Lu, Detlef H. Heck, Robert W. Williams

Faculty Publications

calreticulin, Animals, Chromosome Mapping, Mammalian Chromosomes, Gene Expression Regulation, Genetic Linkage, Genome-Wide Association Study. Inbred C57BL Mice, Inbred DBA Mice, Quantitative Trait Loci, Sodium-Potassium-Exchanging ATPase/genetics, Atp1a2 protein, Sodium-Potassium-Exchanging ATPase, feeding behavior, drinking behavior, mice, central pattern generator, genetic control

Mutation At The Human D1s80 Minisatellite Locus, Kuppareddi Balamurugan

Faculty Publications

Little is known about the general biology of minisatellites. The purpose of this study is to examine repeat mutations from the D1S80 minisatellite locus by sequence analysis to elucidate the mutational process at this locus. This is a highly polymorphic minisatellite locus, located in the subtelomeric region of chromosome 1. We have analyzed 90,000 human germline transmission events and found seven (7) mutations at this locus. The D1S80 alleles of the parentage trio, the child, mother, and the alleged father were sequenced and the origin of the mutation was determined. Using American Association of Blood Banks (AABB) guidelines, we found …

Identification Of Cellular Functions Of Cardiolipin As Physiological Modifiers Of Barth Syndrome, Amit Shridhar Joshi

Wayne State University Dissertations

Cardiolipin (CL) is an anionic phospholipid synthesized in the mitochondrial inner membrane. Perturbation of CL metabolism leads to Barth syndrome (BTHS), a life threatening genetic disorder. I utilized genetic, biochemical and cell biological approaches in yeast to elucidate the cellular functions of CL. Understanding the functions of CL is expected to shed light on the pathology and possible treatments for BTHS.

BTHS is caused by mutations in TAZ1, which encodes a CL remodeling enzyme called tafazzin. BTHS patients exhibit a wide range of clinical presentations, indicating that physiological modifiers influence the BTHS phenotype. A targeted synthetic lethality screen was performed …

Effects Of Ions On The Activity Of Peptidyl-Trna Hydrolase, Blake Holloway

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

No abstract provided.