Digital Commons Network^™

Impacts Of Covid-19 On Global Healthcare Management And Research, Stephanie Autore, Santanu De

Biology Faculty Articles

The Coronavirus Infectious Disease 2019 (COVID-19) pandemic has affected most nations at all levels of functioning, individual to governmental. Therefore, it is imperative to evaluate the effects the virus has had on one of the most important socioeconomic global sectors, healthcare. This literature review explores key, recent research and management strategies that have been undertaken in healthcare systems around the world in order to make meaningful attempts at identifying the etiology, diagnosis, and treatment of the disease, and combating the spread of this deadly virus. Healthcare facilities have implemented a variety of changes, all geared towards reducing non-emergency patient visits …

Antibiotics Overuse And Bacterial Resistance, Mir Saleem, Brett Deters, Adam De La Bastide, Martha Korzen

Biology Faculty Articles

Antibiotic usage has become very widespread, as they are used to treat so many infectious diseases today. Antimicrobial agents exert their actions via different mechanisms including blockage of cell wall synthesis, interference of protein and/or nucleic acid synthesis, interruption of cell membrane structure, and inhibition of a metabolic pathway. The treatment of bacterial infections with antimicrobial agents has become more difficult due to the capability of bacteria to develop resistance to antibiotics. Erroneous diagnosing, misconceptions, and improper physician-patient dynamics have led to overuse of antibiotics and the emergence of drug-resistant bacteria. Bacterial colonies have been shown to confer advantageous genetic …

Pvsripo Effect On Cancer, Vishal Jindal, Matthew Lee, Darshan Rola, Mir Saleem

Biology Faculty Articles

PVSRIPO, a variant of the poliovirus, is a revolutionary virus that demonstrates key characteristics for oncolytic virotherapy due to its ability to attack glioblastomas. The first criteria that PVSRIPO demonstrates is tumor-targeting tropism. PVSRIPO binds to nectin-like molecule 5 (Necl-5), a poliovirus receptor (PVR), found on different types of cancers such as lung cancer, colorectal cancer, and glioblastomas. This allows the virus to have a high binding affinity to tumor cells. Secondly, after modifying the poliovirus by substituting its internal ribosome entry site (IRES) with the Human Rhinovirus 2's (HRV2) IRES, the poliovirus becomes PVSRIPO, an attenuated version of the …

Role Of Genes In Obesity, Hanna Mathew, Mir Saleem

Biology Faculty Articles

Obesity is the outcome of an extreme difference between the energy intake and the energy expended, which leads to severe weight gain. The two main factors of obesity are environmental influences and genetics, but the extent of the genetic contribution to obesity continues to be unknown. Multiple studies using different tools have been used to support the significance of the genetic influence on obesity, such as twin and adoption studies, race/ethnicity, and mouse models. The use of mouse models has allowed for the greatest expansion of knowledge on the genetics behind obesity, and advancements continue to be made to this …

Analytical “Bake-Off” Of Whole Genome Sequencing Quality For The Genome Russia Project Using A Small Cohort For Autoimmune Hepatitis, Daria V. Zhernakova, Sergei Kliver, Nikolay Cherkasov, Gaik Tamazian, Mikhail Rotkevich, Ksenia Krasheninnikova, Igor Evsyukov, Sviatoslav Sidorov, Pavel Dobrynin, Andrey A. Yurchenko, Valentin Shimansky, Irina V. Shcherbakova, Andrey S. Glotov, David L. Valle, Minzhong Tang, Emilia Shin, Kathleen B. Schwarz, Stephen James O'Brien

Biology Faculty Articles

A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects. We assessed calling of SNPs, indels, copy number variation, and the speed of WGS throughput promised. Twenty separate QC analyses showed high similarities among the sequence quality and called genotypes. The ten genomes tested by the centers included eight …

Periodontitis In Patients With Type 2 Diabetes Mellitus, Simran Agarwal, Deepthi Gangaram, Mir Saleem

Biology Faculty Articles

Periodontitis is a chronic, inflammatory disease that is characterized by swollen gums, degradation of jaw structure, and potentially tooth loss. Like Periodontitis, Type 2 Diabetes Mellitus is also highly prevalent and largely multifactorial. Type 2 Diabetes is a condition in which higher than normal blood glucose levels cannot be properly maintained as the body’s normal mechanism of maintaining proper blood glucose levels, the release of insulin from pancreatic islet β-cells, becomes ineffective. The purpose of this literature review is to explore the relationship between the incidences of Periodontitis and Type 2 Diabetes. The risk that Type 2 Diabetes poses for …

Neuropsychiatric Aspects Of Near-Death Experience, Jerod Buchta, Mir Saleem

Biology Faculty Articles

Throughout human history, there have been numerous reports of a baffling process when individuals have come to the brink of death. This process, referred to as near death experiences (NDEs), cause an individual to experience events that even the most advanced science can still not answer. This review serves as a reference for the factors, phenomenology, and measurement techniques for near death experiences as well as summarizing these experiences in certain conditions, such as cardiac arrest and admission of anesthetics. Discussed are the theories, effects, analyses of specific processes involved pertaining to experiences of those who walked along the edge …

Yawns Are Cool, Andrew C. Gallup, Omar T. Eldakar

Biology Faculty Articles

Although we yawn each and every day, most people have little understanding of why we do it. In fact, the function of yawning has remained mysterious for centuries, even among scientists, and this has only changed quite recently. Contrary to what people have believed for a long time, it is now understood that yawns have nothing to do with breathing or the amount of oxygen we are taking in. Instead, new and growing research has revealed that yawns serve as a brain cooling mechanism. This new perspective on yawning as a response to elevated brain temperature has transformed our understanding …

A Mutation In Ltbp2 Causes Congenital Glaucoma In Domestic Cats (Felis Catus), Markus H. Kuehn, Koren A. Lipsett, Marilyn Menotti-Raymond, S. Scott Whitmore, Todd E. Scheetz, Victor A. David, Stephen J. O'Brien, Zhongyuan Zhao, Jackie K. Jens, Elizabeth M. Snella, N. Matthew Ellinwood, Gillian J. Mclellan

Biology Faculty Articles

The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by …

Science Alive!: Connecting With Elementary Students Through Science Exploration, Aarti Raja, Emily F. Schmitt Lavin, Tamara Gali, Kaitlin Donovan

Biology Faculty Articles

A novel program called Science Alive! was developed by undergraduate faculty members, K–12 school teachers, and undergraduate students to enrich science, technology, engineering, and mathematics (STEM) literacy at community schools located near the university. The ultimate goal of the program is to bolster the scientific knowledge and appreciation of local area students and community members and serve as a model for similar programs. Through the program, we observed that elementary school students made gains toward learning their grade-level science curricula after a hands-on learning experience and had fun doing these hands-on activities. Through the program, undergraduate students, working with graduate …

The Genome Russia Project: Closing The Largest Remaining Omission On The World Genome Map, T. K. Oleksyk, Vladimir Brukhin, Stephen J. O'Brien

Biology Faculty Articles

We are witnessing the great era of genome exploration of the world, as genetic variation in people is being detailed across multiple varied world populations in an effort unprecedented since the first human genome sequence appeared in 2001. However, these efforts have yet to produce a comprehensive mapping of humankind, because important regions of modern human civilization remain unexplored. The Genome Russia Project promises to fill one of the largest gaps, the expansive regions across the Russian Federation, informing not just medical genomics of the territories, but also the migration settlements of historic and pre-historic Eurasian peoples.

Genome-Wide Association And Trans-Ethnic Meta-Analysis For Advanced Diabetic Kidney Disease: Family Investigation Of Nephropathy And Diabetes (Find), Sudha K. Iyengar, John R. Sedor, Barry I. Freedman, W. H. Linda Kao, Matthias Kretzler, Benjamin J. Keller, Hanna E. Abboud, Sharon G. Adler, Lyle G. Best, Donald W. Bowden, Allison Burlock, Yii-Der Ida Chen, Shelley A. Cole, Mary E. Comeau, Jeffrey M. Curtis, Jasmin Divers, Christiane Drechsler, Ravi Duggirala, Robert C. Elston, Xiuqing Guo, Huateng Huang, Michael M. Hoffmann, Barbara V. Howard, Eli Ipp, Paul L. Kimmel, Michael J. Klag, William C. Knowler, Orly F. Kohn, Tennille S. Leak, David J. Leehey, Man Li, Alka Malhotra, Winfried Marz, Viji Nair, Robert G. Nelson, Susanne B. Nicholas, Stephen J. O'Brien, Madeleine V. Pahl, Rulan S. Parekh, Marcus G. Pezzolesi, Rebekah S. Rasooly, Charles N. Rotimi, Jerome I. Rotter, Jeffrey R. Schelling, Michael F. Seldin, Vallabh O. Shah, Adam M. Smiles, Michael W. Smith, Kent D. Taylor, Farook Thameem, Denyse P. Thornley-Brown, Barbara J. Truitt, Christoph Wanner, E. Jennifer Weil, Cheryl Winkler, Philip G. Zager, Robert P. Igo Jr., Robert L. Hanson, Carl D. Langefeld, Family Investigation Of Nephropathy And Diabetes (Find) Research Group

Biology Faculty Articles

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, …

Gwatch: A Web Platform For Automated Gene Association Discovery Analysis, Anton Svitin, Sergey Malov, Nikolay Cherkasov, Paul Geerts, Mikhail Rotkevich, Pavel Dobrynin, Andrey Shevchenko, Li Guan, Jennifer L. Troyer, Sher L. Hendrickson, Holli Hutcheson Dilks, T. K. Oleksyk, Sharyne Donfield, Edward Gomperts, Douglas A. Jabs, Efe Sezgin, Mark Van Natta, P. Richard Harrigan, Zabrina L. Brumme, Stephen J. O'Brien

Biology Faculty Articles

Background: As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations.

Findings: Here we present a dynamic web-based platform – GWATCH – that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication …

Evaluation And Integration Of Genetic Signature For Prediction Risk Of Nasopharyngeal Carcinoma In Southern China, Xiuchan Guo, Cheryl Winkler, Ji Li, Li Guan, Minzhong Tang, Jian Liao, Hong Deng, Guy De The, Yi Zeng, Stephen J. O'Brien

Biology Faculty Articles

Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC). Results …

Genome-Wide And Differential Proteomic Analysis Of Hepatitis B Virus And Aflatoxin B1 Related Hepatocellular Carcinoma In Guangxi, China, Lu-Nan Qi, Le-Qun Qi, Yuan-Yuan Chen, Zhao-Hong Chen, Tao Bai, Bang-De Xiang, Xiao Qin, Kai-Yin Xiao, Min-Hao Peng, Zhi-Ming Liu, Tang-Wei Liu, Xue Qin, Shan Li, Ze-Guang Han, Zeng-Nan Mo, Regina M. Santella, Cheryl Winkler, Stephen J. O'Brien, Tao Peng

Biology Faculty Articles

Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently …

A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, Istvan Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. Mclaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio Lopez-Galindez, Concepcion Casado, Andri Rauch, Huldrych F. Gunthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltan Kutalik, Todd M. Allen, Viktor Muller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay

Biology Faculty Articles

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10⁻¹²). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation …

Association Study Of Common Genetic Variants And Hiv- 1 Acquisition In 6,300 Infected Cases And 7,200 Controls, Paul J. Mclaren, Cedric Coulonges, Stephan Ripke, Leonard H. Van Den Berg, Susan Buchbinder, Mary Carrington, Andrea Cossarizza, Judith Dalmau, Steven G. Deeks, Olivier Delaneau, Andrea De Luca, James J. Goedert, David W. Haas, Joshua T. Herbeck, Sekar Kathiresan, Gregory D. Kirk, Olivier Lambotte, Ma Luo, Simon Mallal, Danielle Van Manen, Javier Martinez-Picado, Florencia Pereyra, Francis A. Plummer, Guido Poli, Ying Qi, Pierre Rucart, Manj S. Sandhu, Patrick R. Shea, Hanneke Schuitemaker, Ioannis Theodorou, Fredrik Vannberg, Jan Veldink, Bruce D. Walker, Amy C. Weintrob, Cheryl Winkler, Steven M. Wolinsky, Amalio Telenti, David B. Goldstein, Paul I. W. De Bakker, Jean-Francois Zagury, Jacques Fellay

Biology Faculty Articles

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the …

Host Genomic Influences On Hiv/Aids, Stephen J. O'Brien, Sher L. Hendrickson

Biology Faculty Articles

The AIDS era has seen multiple advances in the power of genetics research; scores of host genetic protective factors have been nominated and several have translated to the bedside. We discuss how genomics may inform HIV/AIDS prevention, treatment and eradication.

The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, Minzhong Tang, J. A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl Winkler, Mary Carrington, Guy De The, Yi Zeng, Stephen J. O'Brien

Biology Faculty Articles

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (P_{HLA-A-aa-site-62}= 7.4×10⁻²⁹; P _{HLA-B-aa-site-116}= 6.5×10⁻¹⁹; P _{HLA-C-aa-site-156} = 6.8×10 …

Emerging Viruses In The Felidae: Shifting Paradigms, Stephen J. O'Brien, Jennifer L. Troyer, Meredith Brown, Warren E. Johnson, Agostinho Antunes, Melody E. Roelke, Jill Pecon-Slattery

Biology Faculty Articles

The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important …

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 …

Role Of Exonic Variation In Chemokine Receptor Genes On Aids: Ccrl2 F167y Association With Pneumocystis Pneumonia, Ping An, Rongling Li, Ji Ming Wang, Teizo Yoshimura, Munehisa Takahashi, Ram Samudralal, Stephen J. O'Brien, John Phair, James J. Goedert, Gregory D. Kirk, Jennifer L. Troyer, Efe Sezgin, Susan Buchbinder, Sharyne Donfield, George W. Nelson, Cheryl Winkler

Biology Faculty Articles

Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 andCCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In …

Evolution Of A Major Drug Metabolizing Enzyme Defect In The Domestic Cat And Other Felidae: Phylogenetic Timing And The Role Of Hypercarnivory, Binu Shrestha, J. Michael Reed, Philip T. Starks, Gretchen E. Kaufman, Jared V. Goldstone, Melody E. Roelke, Stephen J. O'Brien, Klaus-Peter Koepfli, Laurence Frank, Michael H. Court

Biology Faculty Articles

The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional …

Genetic Variants In Nuclear-Encoded Mitochondrial Genes Influence Aids Progression, Sher L. Hendrickson, J. A. Lautenberger, Leslie Wei Chinn, Michael Malasky, Lawrence Kingsley, James J. Goedert, Gregory D. Kirk, Edward Gomperts, Susan Buchbinder, Jennifer L. Troyer, Stephen J. O'Brien

Biology Faculty Articles

Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.

Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 …

Genetic Polymorphisms Of Cyp2e1, Gstp1, Nqo1 And Mpo And The Risk Of Nasopharyngeal Carcinoma In A Han Chinese Population Of Southern China, Xiuchan Guo, Yi Zeng, Hong Deng, Jian Liao, Yuming Zheng, Ji Li, Bailey Kessing, Stephen J. O'Brien

Biology Faculty Articles

Background

Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.

Methods

Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 …

Accounting For Multiple Comparisons In A Genome-Wide Association Study (Gwas), Randall C. Johnson, George W. Nelson, Jennifer L. Troyer, J. A. Lautenberger, Bailey Kessing, Cheryl Winkler, Stephen J. O'Brien

Biology Faculty Articles

Background

As we enter an era when testing millions of SNPs in a single gene association study will become the standard, consideration of multiple comparisons is an essential part of determining statistical significance. Bonferroni adjustments can be made but are conservative due to the preponderance of linkage disequilibrium (LD) between genetic markers, and permutation testing is not always a viable option. Three major classes of corrections have been proposed to correct the dependent nature of genetic data in Bonferroni adjustments: permutation testing and related alternatives, principal components analysis (PCA), and analysis of blocks of LD across the genome. We consider …

Common Genetic Variation And The Control Of Hiv-1 In Humans, Jacques Fellay, Dongliang Ge, Kevin V. Shianna, Sara Colombo, Bruno Ledergerber, Elizabeth T. Cirulli, Thomas J. Urban, Kunlin Zhang, Curtis Gumbs, Jason P. Smith, Antonella Castagna, Alessandro Cozzi-Lepri, Andrea De Luca, Philippa Easterbrook, Huldrych F. Gunthard, Simon Mallal, Cristina Mussini, Judith Dalmau, Javier Martinez-Picado, Jose M. Miro, Niels Obel, Steven M. Wolinsky, Jeremy J. Martinson, Roger Detels, Joseph Margolick, Lisa Jacobson, Patrick Descombes, Stylianos E. Antonarakis, Jacques S. Beckmann, Stephen J. O'Brien, Norman L. Letvin, Andrew J. Mcmichael, Barton F. Haynes, Mary Carrington, Sheng Feng, Amalio Telenti, David B. Goldstein, Niaid Center For Hiv/Aids Vaccine Immunology (Chavi)

Biology Faculty Articles

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of …

Ccl3l1 And Hiv/Aids Susceptibility, Thomas J. Urban, Amy C. Weintrob, Jacques Fellay, Sara Colombo, Kevin V. Shianna, Curtis Gumbs, Margalida Rotger, Kimberly Pelak, Kristen K. Dang, Roger Detels, Jeremy J. Martinson, Stephen J. O'Brien, Norman L. Letvin, Andrew J. Mcmichael, Barton F. Haynes, Mary Carrington, Amalio Telenti, Nelson L. Michael, David B. Goldstein

Biology Faculty Articles

No abstract provided.

Identifying Selected Regions From Heterozygosity And Divergence Using A Light-Coverage Genomic Dataset From Two Human Populations, T. K. Oleksyk, Kai Zhao, Francisco M. De La Vega, Dennis A. Gilbert, Stephen J. O'Brien, Michael W. Smith

Biology Faculty Articles

When a selective sweep occurs in the chromosomal region around a target gene in two populations that have recently separated, it produces three dramatic genomic consequences: 1) decreased multi-locus heterozygosity in the region; 2) elevated or diminished genetic divergence (F_ST) of multiple polymorphic variants adjacent to the selected locus between the divergent populations, due to the alternative fixation of alleles; and 3) a consequent regional increase in the variance of F_ST (S²F_ST) for the same clustered variants, due to the increased alternative fixation of alleles in the loci surrounding the selection target. In …

Genetic Characterization Of Feline Leukemia Virus From Florida Panthers, Meredith Brown, Mark W. Cunningham, Alfred L. Roca, Jennifer L. Troyer, Warren E. Johnson, Stephen J. O'Brien

Biology Faculty Articles

From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were …