Genetics and Genomics Commons^™

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

Molecular Basis Of A Novel Adaptation To Hypoxic-Hypercapnia In A Strictly Fossorial Mole, Kevin L. Campbell, Jay F. Storz, Anthony V. Signore, Hideaki Moriyama, Kenneth C. Catania, Alexander P. Payson, Joseph Bonaventura, Jörg Stetefeld, Roy E. Weber

Jay F. Storz Publications

Background: Elevated blood O₂ affinity enhances survival at low O₂ pressures, and is perhaps the best known and most broadly accepted evolutionary adjustment of terrestrial vertebrates to environmental hypoxia. This phenotype arises by increasing the intrinsic O₂ affinity of the hemoglobin (Hb) molecule, by decreasing the intracellular concentration of allosteric effectors (e.g., 2,3-diphosphoglycerate; DPG), or by suppressing the sensitivity of Hb to these physiological cofactors.

Results: Here we report that strictly fossorial eastern moles (Scalopus aquaticus) have evolved a low O₂ affinity, DPG-insensitive Hb - contrary to expectations for a mammalian species that is …

Phenotypic Plasticity And Genetic Adaptation To High-Altitude Hypoxia In Vertebrates, Jay F. Storz, Graham R. Scott, Zachary A. Cheviron

Jay F. Storz Publications

High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent …

Genetic Differences In Hemoglobin Function Between Highland And Lowland Deer Mice, Jay F. Storz, Amy M. Runck, Hideaki Moriyama, Roy E. Weber, Angela Fago

Jay F. Storz Publications

In high-altitude vertebrates, adaptive changes in blood–O₂ affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O₂ affinity and/or responsiveness to allosteric effectors that modulate Hb–O₂ affinity. This mode of genotypic specialization is considered typical of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O₂ affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal. The results of a combined genetic and proteomic analysis revealed that deer mice harbor …

Genome3d: A Viewer-Model Framework For Integrating And Visualizing Multi-Scale Epigenomic Information Within A Three-Dimensional Genome, Thomas M. Asbury, Matt Mitman, Jijun Tang, W. Jim Zheng

Faculty Publications

Background
New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation.

Results
We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order …

Interleukin 6 And 8 Gene Expression Responses To Resistance Exercise And The Correlation To Muscle Mass, Vivien Massie

Theses : Honours

The post exercise inflammatory response is a key signalling mechanism regulating muscle protein synthesis. The purpose of this research was firstly to determine whether muscle mass in non-strength trained individuals was associated with the inflammatory muscle gene response after a single bout of eccentric muscle loading. Secondly, to determine whether changes in muscle cross-sectional area after a chronic increase in muscle loading (resistance training) is related to the inflammatory gene response to a single bout of muscle loading. Eleven male participants (21.6 ± 4.1 years) volunteered for this study. Each participant completed a preliminary testing session that consisted of two …

High-Density Screening Reveals A Different Spectrum Of Genomic Aberrations In Chronic Lymphocytic Leukemia Patients With ‘Stereotyped’ Ighv3-21 And Ighv4-34 B-Cell Receptors, Millaray Marincevic, Nicola Cahill, Rebeqa Gunnarsson, Anders Isaksson, Mahmoud Mansouri, Hanna Göransson, Markus Rasmussen, Mattias Jansson, Fergus Ryan, Karin Karlsson, Hans-Olov Adami, Fred Davi, Jesper Jurlander, Gunnar Juliusson, Kostas Stamatopoulos, Richard Rosenquist

Articles

Background The existence of multiple subsets of chronic lymphocytic leukemia expressing ‘stereotyped’ Bcell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that ‘stereotypy’ may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and …

Genetic Connections Between Neurological Disorders And Cholesterol Metabolism, Ingemar Bjorkhem, Valerio Leoni, Steve Meaney

Articles

Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in another review in this Thematic Series, defects in cholesterol metabolism (cerebrotendinous xanthomatosis) and intracellular transport (Niemann Pick Syndrome) lead to neurological disease. A subform of hereditary spastic paresis (type SPG5) and Huntington's disease are neurological diseases with mutations in genes that are of importance for cholesterol metabolism. Neurodegeneration is generally …

Insights Into Genome Functional Organisation Through The Analysis Of Interaction Networks, Andre Masella

Theses and Dissertations (Comprehensive)

Using computational techniques to identify orthology and operon structure, it is possible to find functional interactions between genes, which, together, define the genetic interactome. These large networks contain information about the relationships between phenotypes in organisms as genes responsible for related abilities are often co-regulated and reasserting of these genes can be detected in the operon structure. However, these networks are too large to analyse by hand In order to practically analyse the networks, a computational tool, gisql, was developed and, using this tool, the connectivity patterns in the genetic interactome can be analysed to understand high-level organisation of …