Genetics and Genomics Commons^™

Molecular Evolution And The Role Of Oxidative Stress In The Expansion And Functional Diversification Of Cytosolic Glutathione Transferases, Rute R. Da Fonseca, Warren E. Johnson, Stephen J. O'Brien, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

Background: Cytosolic glutathione transferases (cGST) are a large group of ubiquitous enzymes involved in detoxification and are well known for their undesired side effects during chemotherapy. In this work we have performed thorough phylogenetic analyses to understand the various aspects of the evolution and functional diversification of cGSTs. Furthermore, we assessed plausible correlations between gene duplication and substrate specificity of gene paralogs in humans and selected species, notably in mammalian enzymes and their natural substrates.

Results: We present a molecular phylogeny of cytosolic GSTs that shows that several classes of cGSTs are more ubiquitous and thus have an …

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 …

Genome 10k: A Proposal To Obtain Whole-Genome Sequence For 10000 Vertebrate Species, David Haussler, Stephen J. O'Brien, Oliver A. Ryder, F. Keith Barker, Michele Clamp, Andrew J. Crawford, Robert Hanner, Olivier Hanotte, Warren E. Johnson, Jimmy A. Mcguire, Webb Miller, Robert W. Murphy, William J. Murphy, Frederick H. Sheldon, Barry Sinervo, Byrappa Venkatesh, Edward O. Wiley, Fred W. Allendorf, George Amato, C. Scott Baker, Aaron Bauer, Albano Beja-Pereira, Eldredge Bermingham, Giacomo Bernardi, Cibele R. Bonvicino, Sydney Brenner, Terry Burke, Joel Cracraft, Mark Diekhans

Biology Faculty Articles

The human genome project has been recently complemented by whole-genome assessment sequence of 32 mammals and 24 nonmammalian vertebrate species suitable for comparative genomic analyses. Here we anticipate a precipitous drop in costs and increase in sequencing efficiency, with concomitant development of improved annotation technology and, therefore, propose to create a collection of tissue and DNA specimens for 10000 vertebrate species specifically designated for whole-genome sequencing in the very near future. For this purpose, we, the Genome 10K Community of Scientists (G10KCOS), will assemble and allocate a biospecimen collection of some 16203 representative vertebrate species spanning evolutionary diversity across living …

Every Genome Sequence Needs A Good Map, Harris A. Lewin, Denis M. Larkin, J. U. Pontius, Stephen J. O'Brien

Biology Faculty Articles

No abstract provided.

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.

Genetics And Pathogenesis Of Feline Infectious Peritonitis Virus, Meredith Brown, Jennifer L. Troyer, Jill Pecon-Slattery, M. Roelke-Parker, Stephen J. O'Brien

Biology Faculty Articles

Feline coronavirus (FCoV) is endemic in feral cat populations and cat colonies, frequently preceding outbreaks of fatal feline infectious peritonitis (FIP). FCoV exhibits 2 biotypes: the pathogenic disease and a benign infection with feline enteric coronavirus (FECV). Uncertainty remains regarding whether genetically distinctive avirulent and virulent forms coexist or whether an avirulent form mutates in vivo, causing FIP. To resolve these alternative hypotheses, we isolated viral sequences from FCoV-infected clinically healthy and sick cats (8 FIP cases and 48 FECV-asymptomatic animals); 735 sequences from 4 gene segments were generated and subjected to phylogenetic analyses. Viral sequences from healthy cats were …

The Taming Of The Cat, Carlos A. Driscoll, Juliet Clutton-Brock, Andrew C. Kitchener, Stephen J. O'Brien

Biology Faculty Articles

This article discusses research into the evolution of domesticated cats, which is complicated by the fact that they do not appear to serve humans. Although several species are morphologically similar, genetic research focusing on mitochondrial DNA and genetic microsatellites found that domesticated cats descended from F. sylvestris lybica. Archaeological research indicating cats came to live with humans as the prevalence of house mice in agricultural settlements increased is noted. Insets: The House Cat's Ancestor; Early Domestication; From Wild to Mild; The Truth about Cats and Dogs

Mitochondrial Phylogeography Illuminates The Origin Of The Extinct Caspian Tiger And Its Relationship To The Amur Tiger, Carlos A. Driscoll, Nobuyuki Yamaguchi, Gila Kahila Bar-Gal, Alfred L. Roca, Shu-Jin Luo, David W. Macdonald, Stephen J. O'Brien

Biology Faculty Articles

The Caspian tiger (Panthera tigris virgata) flourished in Central Asian riverine forest systems in a range disjunct from that of other tigers, but was driven to extinction in 1970 prior to a modern molecular evaluation. For over a century naturalists puzzled over the taxonomic validity, placement, and biogeographic origin of this enigmatic animal. Using ancient-DNA (aDNA) methodology, we generated composite mtDNA haplotypes from twenty wild Caspian tigers from throughout their historic range sampled from museum collections. We found that Caspian tigers carry a major mtDNA haplotype differing by only a single nucleotide from the monomorphic haplotype found across …

The Evolutionary Dynamics Of The Lion Panthera Leo Revealed By Host And Viral Population Genomics, Agostinho Antunes, Jennifer L. Troyer, Melody E. Roelke, Jill Pecon-Slattery, Craig Packer, Christiaan Winterbach, Graham Hemson, Laurence G. Frank, Philip Stander, Ludwig Siefert, Margaret Driciru, Paul J. Funston, Kathy A. Alexander, Katherine C. Prager, Gus Mills, David E. Wildt, Mitch E. Bush, Stephen J. O'Brien, Warren E. Johnson

Biology Faculty Articles

The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV_Ple), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, …

Mitochondrial Genomes Reveal An Explosive Radiation Of Extinct And Extant Bears Near The Miocene-Pliocene Boundary, Johannes Krause, Tina Unger, Aline Nocon, Anna-Sapfo Malaspinas, Sergios-Orestis Kolokotronis, Mathias Stiller, Leopoldo Soibelzon, Helen Spriggs, Paul H. Dear, Adrian W. Briggs, Sarah C. E. Bray, Stephen J. O'Brien, Gernot Rabeder, Paul Matheus, Alan Cooper, Montgomery Slatkin, Svante Paabo, Michael Hofreiter

Biology Faculty Articles

Background: Despite being one of the most studied families within the Carnivora, the phylogenetic relationships among the members of the bear family (Ursidae) have long remained unclear. Widely divergent topologies have been suggested based on various data sets and methods.

Results: We present a fully resolved phylogeny for ursids based on ten complete mitochondrial genome sequences from all eight living and two recently extinct bear species, the European cave bear (Ursus spelaeus) and the American giant short-faced bear (Arctodus simus). The mitogenomic data yield a well-resolved topology for ursids, with the sloth bear at the basal …

Sequences, Annotation And Single Nucleotide Polymorphism Of The Major Histocompatibility Complex In The Domestic Cat, Naoya Yuhki, James C. Mullikin, Thomas W. Beck, Robert M. Stephens, Stephen J. O'Brien

Biology Faculty Articles

Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and …

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 …

Functions, Structure, And Read-Through Alternative Splicing Of Feline Apobec3 Genes, Carsten Munk, Thomas W. Beck, Jorg Zielonka, Agnes Hotz-Wagenblatt, Sarah Chareza, Marion Battenberg, Jens Thielebein, Klaus Cichutek, Ignacio G. Bravo, Stephen J. O'Brien, Martin Lochelt, Naoya Yuhki

Biology Faculty Articles

Background:

Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene.

Results:

Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three …

The Adaptive Evolution Of The Mammalian Mitochondrial Genome, Rute R. Da Fonseca, Warren E. Johnson, Stephen J. O'Brien, Maria J. Ramos, Agostinho Antunes

Biology Faculty Articles

Background

The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.

Results

Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to …

Genomic Organization, Sequence Divergence, And Recombination Of Feline Immunodeficiency Virus From Lions In The Wild, Jill Pecon-Slattery, Carrie L. Mccracken, Jennifer L. Troyer, Sue Vandewoude, Melody E. Roelke, Kerry Sondgeroth, Christiaan Winterbach, Stephen J. O'Brien

Biology Faculty Articles

Background

Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion.

Results

In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes …

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 …

Initial Sequence And Comparative Analysis Of The Cat Genome, J. U. Pontius, James C. Mullikin, Douglas R. Smith, Agencourt Bioscience Corporation, Kerstin Lindblad-Toh, Sante Gnerre, Michele Clamp, Jean Chang, R. Stephens, Beena A. Neelam, Natalia Volfovsky, Alejandro A. Schaffer, R. Agarwala, Kristina Narfstrom, William J. Murphy, Urs Giger, Alfred L. Roca, Agostinho Antunes, Marilyn Menotti-Raymond, Naoya Yuhki, Jill Pecon-Slattery, Warren E. Johnson, Guillaume Bourque, Glenn Tesler, Nisc Comparative Sequencing Program, Stephen J. O'Brien

Biology Faculty Articles

The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and …

Validation Of A Short Tandem Repeat Multiplex Typing System For Genetic Individualization Of Domestic Cat Samples, Nikia Coomber, Victor A. David, Stephen J. O'Brien, Marilyn Menotti-Raymond

Biology Faculty Articles

Aim To conduct developmental validation studies on a polymerase chain reaction (PCR) based short tandem repeat (STR) multiplex typing system, developed for the purpose of genetic individualization and parentage testing in domestic cat samples.

Methods To evaluate reproducibility of the typing system, the multiplex was amplified using DNA extracted from hair, blood, and buccal samples obtained from the same individual (n = 13). Additional studies were performed to evaluate the system’s species’ specificity, using 26 North American mammalian species and two prokaryotes Sacchromyces and Escherichia coli, sensitivity, and ability to identify DNA mixtures. Patterns of Mendelian inheritance and mutation …

Primate Tnf Promoters Reveal Markers Of Phylogeny And Evolution Of Innate Immunity, Andres Baena, Alan R. Mootnick, James V. Falvo, Alla V. Tsytsykova, Filipa Ligeiro, Ousmane M. Diop, Claudia Brieva, Pascal Gagneux, Stephen J. O'Brien, Oliver A. Ryder, Anne E. Goldfeld

Biology Faculty Articles

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry.

Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, …

Regulatory Polymorphisms In The Cyclophilin A Gene, Ppia, Accelerate Progression To Aids, Ping An, Li Hua Wang, Holli Hutcheson-Dilks, George Nelson, Sharyne Donfield, James J. Goedert, Charles Rinaldo, Susan Buchbinder, Gregory D. Kirk, Stephen J. O'Brien, Cheryl Winkler

Biology Faculty Articles

Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4⁺ T-cell loss (relative hazard = …

Clouded Leopard Phylogeny Revisited: Support For Species Recognition And Population Division Between Borneo And Sumatra, Andreas Wilting, Valerie A. Buckley-Beason, Heike Feldhaar, Jurgen Gadau, Stephen J. O'Brien, K. Eduard Linsenmair

Biology Faculty Articles

Background

The clouded leopard (Neofelis nebulosa) is one of the least known cat species and depletion of their forested habitats puts it under heavy pressure. Recently reclassification of Bornean clouded leopards (N. nebulosa diardi) to species level (N.diardi) was suggested based on molecular and morphological evidence. Since the genetic results were based solely on three Bornean samples we re-evaluated this partition using additional samples of Bornean clouded leopards (N = 7) and we were also able to include specimens from Sumatra (N = 3), which were lacking in previous analysis.

Results

We found strong …

Genetic Protection Against Hepatitis B Virus Conferred By Ccr5Δ32: Evidence That Ccr5 Contributes To Viral Persistence, Chloe L. Thio, Jacquie Astemborski, Arman A. Bashirova, Timothy L. Mosbruger, Spencer Greer, Mallory D. Witt, James J. Goedert, Margaret Hilgartner, Audrey Majesk, Stephen J. O'Brien, David L. Thomas, Mary Carrington

Biology Faculty Articles

Recovery from acute hepatitis B virus (HBV) infection requires a broad, vigorous T-cell response, which is enhanced in mice when chemokine receptor 5 (CCR5) is missing. To test the hypothesis that production of a nonfunctional CCR5 (CCR5Δ32 [a functionally null allele containing a 32-bp deletion]) increases the likelihood of recovery from hepatitis B in humans, we studied 526 persons from three cohorts in which one person with HBV persistence was matched to two persons who recovered from an HBV infection. Recovery or persistence was determined prior to availability of lamivudine. We determined genotypes forCCR5Δ32 …

Polymorphisms Of Cul5 Are Associated With Cd4+ T Cell Loss In Hiv-1 Infected Individuals, Ping An, Priya Duggal, Li Hua Wang, Stephen J. O'Brien, Sharyne Donfield, James J. Goedert, John Phair, Susan Buchbinder, Gregory D. Kirk, Cheryl Winkler

Biology Faculty Articles

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters …

An ∼140-Kb Deletion Associated With Feline Spinal Muscular Atrophy Implies An Essential Lix1 Function For Motor Neuron Survival, John C. Fyfe, Marilyn Menotti-Raymond, Victor A. David, Lars Brichta, Alejandro A. Schaffer, R. Agarwala, William J. Murphy, William J. Wedemeyer, Brittany L. Gregory, Bethany G. Buzzell, Meghan C. Drummond, Brunhilde Wirth, Stephen J. O'Brien

Biology Faculty Articles

The leading genetic cause of infant mortality is spinal muscular atrophy (SMA), a clinically and genetically heterogeneous group of disorders. Previously we described a domestic cat model of autosomal recessive, juvenile-onset SMA similar to human SMA type III. Here we report results of a whole-genome scan for linkage in the feline SMA pedigree using recently developed species-specific and comparative mapping resources. We identified a novel SMA gene candidate, LIX1, in an ~140-kb deletion on feline chromosome A1q in a region of conserved synteny to human chromosome 5q15. Though LIX1 function is unknown, the predicted secondary structure is compatible with …

Kir/Hla Pleiotropism: Protection Against Both Hiv And Opportunistic Infections, Ying Qi, Maureen P. Martin, Xiaojiang Gao, Lisa Jacobson, James J. Goedert, Susan Buchbinder, Gregory D. Kirk, Stephen J. O'Brien, John Trowsdale, Mary Carrington

Biology Faculty Articles

The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS.

Consistent Effects Of Tsg101 Genetic Variability On Multiple Outcomes Of Exposure To Human Immunodeficiency Virus Type 1, Arman A. Bashirova, Gabriela Bleiber, Ying Qi, Holli Hutcheson, Traci Yamashita, Randall C. Johnson, Jie Cheng, Galit Alter, James J. Goedert, Susan Buchbinder, Keith Hoots, David Vlahov, Margaret May, Frank Maldarelli, Lisa Jacobson, Stephen J. O'Brien, Amalio Telenti, Mary Carrington

Biology Faculty Articles

Tumor susceptibility gene 101 (TSG101) encodes a host cellular protein that is appropriated by human immunodeficiency virus type 1 (HIV-1) in the budding process of viral particles from infected cells. Variation in the coding or noncoding regions of the gene could potentially affect the degree of TSG101-mediated release of viral particles. While the coding regions of the gene were found to lack nonsynonymous variants, two polymorphic sites in the TSG101 5' area were identified that were associated with the rate of AIDS progression among Caucasians. These single-nucleotide polymorphisms (SNPs), located at positions -183 and +181 relative to the …

Genetic Factors Leading To Chronic Epstein–Barr Virus Infection And Nasopharyngeal Carcinoma In South East China: Study Design, Methods And Feasibility, Xiu Chan Guo, Kevin Scott, Yan Liu, Michael Dean, Victor David, George W. Nelson, Randall C. Johnson, Holli H. Dilks, J. A. Lautenberger, Bailey Kessing, Janice S. Martenson, Li Guan, Shan Sun, Hong Deng, Yuming Zheng, Guy De The, Jian Liao, Yi Zeng, Stephen J. O'Brien, Cheryl Winkler

Biology Faculty Articles

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample …

Modern Biological Approaches To Folk Medicines And Traditional Antifungal Therapies, Matthew G. Jessulat, Robert P. Smith, Nadereh H. Mir-Rashed, Golshani Ashkan, John Thor Arnason, Myron L. Smith

Biology Faculty Articles

No abstract provided.

The Case For Selection At Ccr5-Δ32, Pardis Sabeti, Emily C. Walsh, Stephen F. Schaffner, Patrick Varilly, Ben Fry, Holli Hutcheson, Mike Cullen, Tarjei S. Mikkelsen, Jessica Roy, Nick Patterson, Richard Cooper, David Reich, David Altshuler, Stephen J. O'Brien, Eric S. Lander

Biology Faculty Articles

The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the past 1,000 y and rose to its present high frequency (5%–14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit …