Genetics and Genomics Commons^™

Analysis Of A Genetic Isolate: The Case Of Carloforte (Italy), R. Robledo, L. Corrias, V. Bachis, N. Puddu, A. Mameli, G. Vona, C. M. Calò

Human Biology Open Access Pre-Prints

We reviewed data collected during several studies concerning the genetic isolate of Carloforte (Sardinia, Italy) and analyzed new data on Y-chromosome markers. Carloforte is also a language island, where people still speaks Tabarchino, an archaic form of Ligurian dialect. Demographic data indicate that, in the early years of its history, Carloforte population was characterized by a high degree of endogamy and consanguinity rates that started to decrease around 1850, when marriages with Sardinian people began to occur more frequently. Cultural factors, mainly language, account for the high endogamy. Genetic data from classical markers, mtDNA and Ychromosome markers confirmed the strong …

The Effect Of Acp1-Ada1 Genetic Interaction On Human Life Span, Nazzareno Lucarini, Valerio Napolioni, Andrea Magrini, Fulvia Gloria

Human Biology Open Access Pre-Prints

Acid phosphatase (ACP1) is a polymorphic enzyme which catalyzes the conversion of flavinmononucleotide (FMN) to riboflavin and regulates the cellular concentration of flavin-adeninedinucleotide (FAD) and, consequently, energy metabolism. Its activity is modulated by adenosine deaminase (ADA1) genotype. Aim of our work is to verify whether individuals with a high proportion of ACP1 f isozyme and carrying ADA*2 allele, displaying the highest phosphatase activity, may have a higher life expectancy. Genomic DNA was extracted from peripheral blood of 569 females and 509 males (18-106 years) randomly recruited from Central Italy. These samples were subdivided into three sexspecific age groups …

Extensive Population Structure In San, Khoe And Mixed Ancestry Populations From Southern Africa Revealed By 44 Short 5-Snp Haplotypes, Carina M. Schlebusch, Himla Soodyall

Human Biology Open Access Pre-Prints

The San and Khoe people currently represent remnant groups of a much larger and widely distributed population of hunter gatherers and pastoralists who had exclusive occupation of southern Africa before the arrival of Bantu-speaking groups in the past 1,200 years and sea-borne immigrants within the last 350 years. Genetic studies (mitochondrial DNA and Y-chromosome) conducted on San and Khoe groups revealed that they harbour some the most divergent lineages found in living peoples throughout the world. Recently, high-density autosomal SNP-array studies confirmed the early divergence of Khoe-San population groups from all other human populations. The present study made use of …

Using The Neandertal And Denisova Genetic Data To Understand The Common Mapt 17q21 Inversion In Modern Humans, Núria Setó-Salvia, Federico Sánchez-Quinto, Eudald Carbonell, Carlos Lorenzo, David Comas, Jordi Clarimón

Human Biology Open Access Pre-Prints

The polymorphic inversion on 17q21, that includes the MAPT gene, represents a unique locus in the human genome characterized by a large region with strong linkage disequilibrium. Two distinct haplotypes, H1 and H2, exist in modern humans, and H1 has been unequivocally related to several neurodegenerative disorders. Recent data indicates that recurrent inversions of this genomic region have occurred through primate evolution, with the H2 haplotype being the ancestral state. Neandertals harbored the H1 haplotype, however until now no data was available for the Denisova hominin. Neandertals and Denisovans are sister groups that share a common ancestor with modern humans. …

A Tale Of Two Haplotypes: The Eda2r/Ar Intergenic Region Is The Most Divergent Genomic Segment Between Africans And East Asians In The Human Genome, Amanda M. Casto, Brenna M. Henn, Jeffery M. Kidd, Carlos D. Bustamante, Marcus W. Feldman

Human Biology Open Access Pre-Prints

Single nucleotide polymorphisms (SNPs) with large allele frequency differences between human populations are relatively rare. The longest run of SNPs with an allele frequency difference of one between the Yoruba of Nigeria and the Han Chinese is found on the long arm of the X chromosome in the intergenic region separating the EDA2R and AR genes. It has been proposed that the unusual allele frequency distributions of these SNPs are the result of a selective sweep affecting African populations that occurred after the Out-of-Africa migration. To investigate the evolutionary history of the EDA2R/AR intergenic region, we characterized the haplotype structure …

Borrelia Burgdorferi Cp32 Bpab Modulates Expression Of The Prophage Nucp Nuclease And Ssbp Single-Stranded Dna-Binding Protein, Alicia M. Chenail, Brandon L. Jutras, Claire A. Adams, Logan H. Burns, Amy Bowman, Ashutosh Verma, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Borrelia burgdorferi BpaB proteins of the spirochete's ubiquitous cp32 prophages are DNA-binding proteins, required both for maintenance of the bacteriophage episomes and for transcriptional regulation of the cp32 erp operons. Through use of DNase I footprinting, we demonstrate that BpaB binds the erp operator initially at the sequence 5′-TTATA-3′. Electrophoretic mobility shift assays indicated that BpaB also binds with high affinity to sites located in the 5′ noncoding regions of two additional cp32 genes. Characterization of the proteins encoded by those genes indicated that they are a single-stranded DNA-binding protein and a nuclease, which we named SsbP and NucP, …

Rosette Iron Deficiency Transcript And Microrna Profiling Reveals Links Between Copper And Iron Homeostasis In Arabidopsis Thaliana, Brian M. Waters, Samuel A. Mcinturf, Ricardo J. Stein

Department of Agronomy and Horticulture: Faculty Publications

Iron (Fe) is an essential plant micronutrient, and its deficiency limits plant growth and development on alkaline soils. Under Fe deficiency, plant responses include up-regulation of genes involved in Fe uptake from the soil. However, little is known about shoot responses to Fe deficiency. Using microarrays to probe gene expression in Kas-1 and Tsu-1 ecotypes of Arabidopsis thaliana, and comparison with existing Col-0 data, revealed conserved rosette gene expression responses to Fe deficiency. Fe-regulated genes included known metal homeostasis-related genes, and a number of genes of unknown function. Several genes responded to Fe deficiency in both roots and rosettes. …

Mutations In Dmrt3 Affect Locomotion In Horses And Spinal Circuit Function In Mice, Lisa S. Andersson, Martin Larhammar, Fatima Memic, Hanna Wootz, Doreen Schwochow, Carl-Johan Rubin, Kalicharan Patra, Thorvaldur Arnason, Lisbeth Wellbring, Göran Hjälm, Freyja Imsland, Jessica Lynn Petersen, Molly E. Mccue, James R. Mickelson, Gus Cothran, Nadav Ahituv, Lars Roepstorff, Sofia Mikko, Anna Vallstedt, Gabriella Lindgren, Leif Andersson, Klas Kullander

Department of Animal Science: Faculty Publications

Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favorable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes …

Genomic Characteristics Of An Environmental Microbial Community Harboring A Novel Human Uncultured Tm7 Bacterium Associated With Oral Diseases, Michael Abrams, David Barton, Eamon Vandaei, Diana Romero, Adam Caldwell, Cleber C. Ouverney

Faculty Publications, Biological Sciences

The diversity of prokaryotes associated with humans has been dominated by uncultured species (not isolated in pure culture). For instance, nearly 80% of the human gut and 68% of the human oral microbes are thought to be uncultured; some of which have been associated with human oral, digestive, vaginal, and cardiovascular diseases. The revalence of uncultured pathogens is expected to continue to increase within the near future. In fact, public databases such as GenBank have nearly quadrupled the number of candidate phyla (those made entirely of uncultured organisms) since the 1980s and currently lists many new lineages of unclassified Bacteria …

Differential Virus Host-Ranges Of The Fuselloviridae Of Hyperthermophilic Archaea: Implications For Evolution In Extreme Environments, Ruben M. Ceballos, Caleb D. Marceau, Joshua O. Marceau, Steven Morris, Adam J. Clore, Kenneth M. Stedman

Biology Faculty Publications and Presentations

An emerging model for investigating virus-host interactions in hyperthermophilic Archaea is the Fusellovirus-Sulfolobus system. The host, Sulfolobus, is a hyperthermophilic acidophile endemic to sulfuric hot springs worldwide. The Fuselloviruses, also known as Sulfolobus Spindle-shaped Viruses (SSVs), are "lemon" or "spindle"-shaped double-stranded DNA viruses, which are also found worldwide. Although a few studies have addressed the host-range for the type virus, Sulfolobus Spindle-shaped Virus 1 (SSV1), using common Sulfolobus strains, a comprehensive host-range study for SSV-Sulfolobus systems has not been performed. Herein, we examine six bona fide SSV strains (SSV1, SSV2, SSV3, SSVL1, SSVK1, SSVRH) and their respective infection characteristics on …

Genomics Of Mature And Immature Olfactory Sensory Neurons, Melissa D. Nickell, Patrick Breheny, Arnold J. Stromberg, Timothy S. Mcclintock

Physiology Faculty Publications

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein …

Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan

Dartmouth Scholarship

Candida albicans, a fungal pathogen of humans, regulates its morphology in response to many environmental cues and this morphological plasticity contributes to virulence. Farnesol, an autoregulatory molecule produced by C. albicans, inhibits the induction of hyphal growth by inhibiting adenylate cyclase (Cyr1). The role of farnesol and Cyr1 in controlling the maintenance of hyphal growth has been less clear. Here, we demonstrate that preformed hyphae transition to growth as yeast in response to farnesol and that strains with increased cyclic AMP (cAMP) signaling exhibit more resistance to farnesol. Exogenous farnesol did not induce the hypha-to-yeast transition in mutants …

Comparative Phylogeography Of Central African Duikers Using Non-Invasive Sampling Methods, Stephan Ntie

LSU New Orleans Theses and Dissertations

The present study sets out to assess patterns of evolutionary diversification in central African duikers (subfamily Cephalophinae). The sampling strategy consisted of collecting geo-referenced duiker feces across 43 sites and seven countries. However, several challenges related to the use of non-invasive samples needed to be addressed prior to large scale DNA amplification. First, the best storage method for obtaining DNA from fecal samples needed to be established. Our study revealed that while silica is best for nuclear microsatellite analyses, RNAlater is the best storage medium for maximal mitochondrial amplification. Moreover, extracting DNA as early as possible always provided the …

Evolution Of Nuclear Integrations Of The Mitochondrial Genome In Great Apes And Their Potential As Molecular Markers, Ivan D. Soto-Calderon

LSU New Orleans Theses and Dissertations

The mitochondrial control region (MCR) has played an important role as a population genetic marker in many taxa but sequencing of complete eukaryotic genomes has revealed that nuclear integrations of mitochondrial DNA (numts) are abundant and widespread across many taxa. If left undetected, numts can inflate mitochondrial diversity and mislead interpretation of phylogenetic relationships. Comparative analyses of complete genomes in humans, orangutans and chimpanzees, and preliminary studies in gorillas have revealed high numt prevalence in great apes, but rigorous comparative analyses across taxa have been lacking.

The present study aimed to systematically compare the evolutionary dynamics of MCR numts in …

Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid

STAR Program Research Presentations

Acetaminophen is a common analgesic and antipyretic. Metabolism of acetaminophen and acetaminophen-induced liver necrosis are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drug is distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Acetaminophen is usually safe and effective when taken as recommended, but consumption at higher levels may lead to liver damage. Additionally, other factors such as alcoholic liver disease, smoking, and malnutrition affect the maximum safe dose of acetaminophen.

A Genetic Survey Of English Sole Populations In The Salish Sea, Elizabeth S. Gutierrez, Gary A. Winans, Jon Baker, Amanda Cope

STAR Program Research Presentations

This summer I interned at the Northwest Fisheries Science Center in Seattle, WA and participated in NOAA’s Salish Sea Project. The Salish Sea Project’s goal is to identify genetically distinctive groups of species in the Salish Sea that may have unique evolutionary and/or adaptive backgrounds. These findings will allow NOAA to promote and monitor the natural production of species in the Salish Sea, to select representative populations for experimental work regarding pollution, ocean acidification and climate change, to contribute to managing the ecosystem for intra- and inter-species diversity, and to help make informed decisions about adaptive management and marine protected …

Antisense Transcription Is Pervasive But Rarely Conserved In Enteric Bacteria, Rahul Raghavan, D. B. Sloan, H. Ochman

Biology Faculty Publications and Presentations

Noncoding RNAs, including antisense RNAs (asRNAs) that originate from the complementary strand of protein-coding genes, are involved in the regulation of gene expression in all domains of life. Recent application of deep-sequencing technologies has revealed that the transcription of asRNAs occurs genome-wide in bacteria. Although the role of the vast majority of asRNAs remains unknown, it is often assumed that their presence implies important regulatory functions, similar to those of other noncoding RNAs. Alternatively, many antisense transcripts may be produced by chance transcription events from promoter-like sequences that result from the degenerate nature of bacterial transcription factor binding sites. To …

Paternal Lineage Analysis Supports An Armenian Rather Than A Central Asian Genetic Origin Of The Hamshenis, Ashot Margaryan, Ashot Harutyunyan, Zaruhi Khachatryan, Armine Khudoyan, Levon Yepiskoposyan

Human Biology Open Access Pre-Prints

The Hamshenis are an isolated geographic group of Armenians with a strong ethnic identity who, until the early decades of the twentieth century, inhabited the Pontus area on the southern coast of the Black Sea. Scholars hold alternative views on their origin, proposing eastern Armenia, western Armenia and Central Asia, respectively, as their most likely homeland. To ascertain whether genetic data from the non-recombining portion of the Y chromosome is supportive any of these suggestions, we screened 82 Armenian males of the Hamsheni descent for 12 biallelic and 6 microsatellite Y-chromosomal markers. These data were compared with the corresponding datasets …

Genetic Susceptibility To Type 2 Diabetes: A Global Meta-Analysis Studying The Genetic Differences In Tunisian Populations, Rym Berhouma, S. Kouidhi, M. Ammar, H. Abid, T. Baroudi, H. Ennafaa, A. Benammar-Elgaaied

Human Biology Open Access Pre-Prints

The present study is the first meta-analysis to evaluate type 2 diabetes (T2D) - associated polymorphisms in cohorts originated from several Tunisian regions. In fact, we evaluated the effect of seven polymorphisms in the following genes; PPARg ( Pro12Ala), TNFα (-308A/G), ENPP1(K121Q), TCF7L2(rs7903146 C/T), MTHFR( C677T), ACE(I/D), CAPN10(3R/2R) on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, centre or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled ORs were computed by the fixed-effects method of Mantel-Haenszel if no heterogeneity between …

Classification Of Genomic Sequences By Latent Semantic Analysis, Samuel F. Way

Department of Electrical and Computer Engineering: Dissertations, Theses, and Student Research

Evolutionary distance measures provide a means of identifying and organizing related organisms by comparing their genomic sequences. As such, techniques that quantify the level of similarity between DNA sequences are essential in our efforts to decipher the genetic code in which they are written.

Traditional methods for estimating the evolutionary distance separating two genomic sequences often require that the sequences first be aligned before they are compared. Unfortunately, this preliminary step imposes great computational burden, making this class of techniques impractical for applications involving a large number of sequences. Instead, we desire new methods for differentiating genomic sequences that eliminate …

Atlas-Based White Matter Analysis In Individuals With Velo-Cardio-Facial Syndrome (22q11.2 Deletion Syndrome) And Unaffected Siblings, Petya D. Radoeva, Ioana L. Coman, Kevin M. Antshel, Wanda Fremont, Christopher Mccarthy, Ashwini Kotkar, Dongliang Wang, Robert J. Shprintzen, Wendy R. Kates

Communication Disorders Faculty Publications

Background: Velo-cardio-facial syndrome (VCFS, MIM#192430, 22q11.2 Deletion Syndrome) is a genetic disorder caused by a deletion of about 40 genes at the q11.2 band of one copy of chromosome 22. Individuals with VCFS present with deficits in cognition and social functioning, high risk of psychiatric disorders, volumetric reductions in gray and white matter (WM) and some alterations of the WM microstructure. The goal of the current study was to characterize the WM microstructural differences in individuals with VCFS and unaffected siblings, and the correlation of WM microstructure with neuropsychological performance. We hypothesized that individuals with VCFS would have decreased indices …

Systems Biology Approaches To Probe Gene Regulation In Bacteria, Diogo F. Troggian Veiga

Dissertations and Theses (Open Access)

Mechanisms that allow pathogens to colonize the host are not the product of isolated genes, but instead emerge from the concerted operation of regulatory networks. Therefore, identifying components and the systemic behavior of networks is necessary to a better understanding of gene regulation and pathogenesis. To this end, I have developed systems biology approaches to study transcriptional and post-transcriptional gene regulation in bacteria, with an emphasis in the human pathogen Mycobacterium tuberculosis (Mtb).

First, I developed a network response method to identify parts of the Mtb global transcriptional regulatory network utilized by the pathogen to counteract phagosomal stresses …

Condensin Ii Promotes The Formation Of Chromosome Territories By Inducing Axial Compaction Of Polyploid Interphase Chromosomes, Christopher R. R. Bauer, Tom A. Hartl, Giovanni Bosco

Dartmouth Scholarship

The eukaryotic nucleus is both spatially and functionally partitioned. This organization contributes to the maintenance, expression, and transmission of genetic information. Though our ability to probe the physical structure of the genome within the nucleus has improved substantially in recent years, relatively little is known about the factors that regulate its organization or the mechanisms through which specific organizational states are achieved. Here, we show that Drosophila melanogaster Condensin II induces axial compaction of interphase chromosomes, globally disrupts interchromosomal interactions, and promotes the dispersal of peri-centric heterochromatin. These Condensin II activities compartmentalize the nucleus into discrete chromosome territories and indicate …

Cytogenetic Biodiversity In The Simulium Johannseni Group (Diptera: Simuliidae), Katherine Gleason

All Theses

Cryptic biodiversity, the presence of suborganismal variation in isomorphic populations of organisms, can have implications for management and conservation. Ecological variation in habitat and host species of populations of the black fly Simulium johannseni suggested the potential for cryptic biodiversity. Polytene chromosomes of larvae belonging to the S. johannseni group of black flies were characterized to discover fixed and polymorphic rearrangements. Larvae of S. johannseni from Wisconsin, South Carolina, and Alabama and of the closely related S. parmatum from South Carolina and Florida were analyzed. Simulium johannseni can be divided into two cytoforms corresponding to geographic location. Cytoform A, found …

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 …

Selaginella Moellendorffii Telomeres: Conserved And Unique Features In An Ancient Land Plant Lineage, Eugene V. Shakirov, Dorothy E. Shippen

Biological Sciences Faculty Research

Telomeres, the essential terminal regions of linear eukaryotic chromosomes, consist of G-rich DNA repeats bound by a plethora of associated proteins. While the general pathways of telomere maintenance are evolutionarily conserved, individual telomere complex components show remarkable variation between eukaryotic lineages and even within closely related species. The recent genome sequencing of the lycophyte Selaginella moellendorffii and the availability of an ever-increasing number of flowering plant genomes provides a unique opportunity to evaluate the molecular and functional evolution of telomere components from the early evolving non-seed plants to the more developmentally advanced angiosperms. Here we analyzed telomere sequence in S. …

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 …

Do Roads Affect Genetic Diversity Of Lizard Populations In Southern New Mexico?, Raul F. Marin, Kevin Floyd, Elizabeth J. Walsh

COURI Symposium Abstracts, Summer 2012

Roads can increase mortality rates, potentially decreasing population sizes. This could increase inbreeding, which will decrease genetic diversity. Decreased genetic diversity can negatively affect long-term viability of populations. We investigated how genetic population structure of the Western Whiptail lizard (Aspidocelis marmorata) is affected by an interstate highway (I-10) in Southern New Mexico. We hypothesize that animals near the road will have lower genetic diversity then individuals farther from the road. We used microsatellites to investigate patterns of genetic diversity (allelic richness and observed heterozygosity) near and away from I-10. Microsatellites are highly variable genetic markers widely used for studying the …

Automated Identification Of Binding Sites Forphosphorylated Ligands In Protein Structures, Dario Ghersi, Roberto Sanchez

Interdisciplinary Informatics Faculty Publications

Phosphorylation is a crucial step in many cellular processes, ranging from metabolic reactions involved in energy transformation to signaling cascades. In many instances, protein domains specifically recognize the phosphogroup. Knowledge of the binding site provides insights into the interaction, and it can also be exploited for therapeutic purposes. Previous studies have shown that proteins interacting with phosphogroups are highly heterogeneous, and no single property can be used to reliably identify the binding site. Here we present an energy-based computational procedure that exploits the protein three-dimensional structure to identify binding sites involved in the recognition of phosphogroups. The procedure is validated …