Genetics and Genomics Commons^™

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 …

Endogenous Retrovirus Insertion In The Kit Oncogene Determines White And White Spotting In Domestic Cats, Victor A. David, Marilyn Menotti-Raymond, Andrea Coots Wallace, Melody E. Roelke, James Kehler, Robert Leighty, Eduardo Eizirik, Steven S. Hannah, George Nelson, Alejandro A. Schaffer, Catherine J. Connelly, Stephen J. O'Brien, David K. Ryugo

Biology Faculty Articles

The Dominant White locus (W) in the domestic cat demonstrates pleiotropic effects exhibiting complete penetrance for absence of coat pigmentation and incomplete penetrance for deafness and iris hypopigmentation. We performed linkage analysis using a pedigree segregating White to identify KIT (Chr. B1) as the feline W locus. Segregation and sequence analysis of the KIT gene in two pedigrees (P1 and P2) revealed the remarkable retrotransposition and evolution of a feline endogenous retrovirus (FERV1) as responsible for two distinct phenotypes of the W locus, Dominant White, and white spotting. A full-length (7125 bp) FERV1 element is associated with white …

Annotated Features Of Domestic Cat – Felis Catus Genome, Gaik Tamazian, Serguei Simonov, Pavel Dobrynin, Alexey Makunin, Anton Logachev, Aleksey Komissarov, Andrey Shevchenko, Vladimir Brukhin, Nikolay Cherkasov, Anton Svitin, Klaus-Peter Koepfli, Joan Pontius, Carlos A. Driscoll, Kevin Blackistone, Cristina Barr, David Goldman, Agostinho Antunes, Javier Quilez, Belen Lorente-Galdos, Can Alkan, Tomas Marques-Bonet, Marilyn Menotti-Raymond, Victor A. David, Kristina Narfstrom, Stephen J. O'Brien

Biology Faculty Articles

Background: Domestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors.

Findings: Here we report a preliminary annotation of the whole genome sequence of Cinnamon, a domestic cat living in Columbia (MO, USA), …

The Dynamic Proliferation Of Cansines Mirrors The Complex Evolution Of Feliforms, Kathryn B. Walters-Conte, Diana L. E. Johnson, Warren E. Johnson, Stephen J. O'Brien, Jill Pecon-Slattery

Biology Faculty Articles

Background: Repetitive short interspersed elements (SINEs) are retrotransposons ubiquitous in mammalian genomes and are highly informative markers to identify species and phylogenetic associations. Of these, SINEs unique to the order Carnivora (CanSINEs) yield novel insights on genome evolution in domestic dogs and cats, but less is known about their role in related carnivores. In particular, genome-wide assessment of CanSINE evolution has yet to be completed across the Feliformia (cat-like) suborder of Carnivora. Within Feliformia, the cat family Felidae is composed of 37 species and numerous subspecies organized into eight monophyletic lineages that likely arose 10 million years ago. Using …

Genome-Wide Mycobacterium Tuberculosis Variation (Gmtv) Database: A New Tool For Integrating Sequence Variations And Epidemiology, Ekaterina N. Chernyaeva, Marina V. Shulgina, Mikhail Rotkevich, Pavel Dobrynin, Serguei Simonov, Egor A. Shitikov, Dmitry S. Ischenko, Irina Y. Karpova, Elena S. Kostryukova, Elena N. Ilina, Vadim M. Govorun, Vyacheslav Y. Zhuravlev, Olga A. Manicheva, Peter K. Yablonsky, Yulia D. Isaeva, Elena Y. Nosova, Igor V. Mokrousov, Anna A. Vyazovaya, Olga V. Narvskaya, Alla L. Lapidus, Stephen J. O'Brien

Biology Faculty Articles

Background

Tuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome.

Description

Here we describe a broadly inclusive unifying Genome-wide Mycobacterium tuberculosis Variation (GMTV) database, (http://mtb.dobzhanskycenter.org) that catalogues genome variations of M. tuberculosis strains collected across Russia. GMTV contains a broad spectrum of data derived from different sources and related to M. …

Gene Discovery And Data Sharing In Genome Wide Association Analyses: Lessons Form Aids Genetic Restriction Genes, Stephen J. O'Brien, Anton Svitin, Sergey Malov, Nikolay Cherkasov, Pavel Dobrynin, Paul Geerts, Jennifer L. Troyer, Sher L. Hendrickson, Efe Sezgin, Holli Hutcheson

Biology Faculty Articles

As genome wide association studies plus whole genome sequence analyses for complex human disease determinants are expanding, it seems useful to develop strategies to facilitate large data sharing, rapid replication and validation of provocative statistical associations that straddle the threshold for genome wide significance. At this conference, we shall announce GWATCH, (Genome Wide Association Tracks Chromosome Highway) a web based data release platform that can freely display and inspect unabridged genome tracked association data without compromising privacy or Informed Consent constrictions, allowing for rapid discovery and replication opportunities. We illustrate the utility with HIV-AIDS resistance genes screened in combined large …

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 …

The Tiger Genome And Comparative Analysis With Lion And Snow Leopard Genomes, Yun Sung Cho, Li Hu, Haolong Hou, Hang Lee, Jiaohui Xu, Soowhan Kwon, Sukhun Oh, Hak-Min Kim, Sungwoong Jho, Sangsoo Kim, Young-Ah Shin, Byung Chul Kim, Hyunmin Kim, Chang-Uk Kim, Shu-Jin Luo, Warren E. Johnson, Klaus-Peter Koepfli, A. Schmidt-Kunzel, Jason A. Turner, L. Marker, Cindy K. Harper, Susan M. Miller, Wilhelm Jacobs, Laura D. Bertola, Tae Hyung Kim, Sunghoon Lee, Qian Zhou, Hyun-Ju Jung, Xiao Xu, Priyvrat Gadhvi, Pengwei Xu, Yingqi Xiong, Yadan Luo, Shengkai Pan, Caiyun Gou, Xiuhui Chu, Jilin Zhang, Sanyang Liu, Jing He, Ying Chen, Linfeng Yang, Yulan Yang, Jiaju He, Sha Liu, Junyi Wang, Chul Hong Kim, Hwanjong Kwak, Jong-Soo Kim, Seungwoo Hwang, Junsu Ko, Chang-Bae Kim, Sangtae Kim, Damdin Bayarlkhagva, Woon Kee Paek, Seong-Jin Kim, Stephen J. O'Brien, Jun Wang, Jong Bhak

Biology Faculty Articles

Tigers and their close relatives (Panthera) are some of the world’s most endangered species. Here we report the de novo assembly of an Amur tiger whole-genome sequence as well as the genomic sequences of a white Bengal tiger, African lion, white African lion and snow leopard. Through comparative genetic analyses of these genomes, we find genetic signatures that may reflect molecular adaptations consistent with the big cats’ hypercarnivorous diet and muscle strength. We report a snow leopard-specific genetic determinant in EGLN1 (Met39>Lys39), which is likely to be associated with adaptation to high altitude. We also detect a …

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 Role Of Gene Duplication And Unconstrained Selective Pressures In The Melanopsin Gene Family Evolution And Vertebrate Circadian Rhythm Regulation, Rui Borges, Warren E. Johnson, Stephen J. O'Brien, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

Melanopsin is a photosensitive cell protein involved in regulating circadian rhythms and other non-visual responses to light. The melanopsin gene family is represented by two paralogs,OPN4x and OPN4m, which originated through gene duplication early in the emergence of vertebrates. Here we studied the melanopsin gene family using an integrated gene/protein evolutionary approach, which revealed that the rhabdomeric urbilaterian ancestor had the same amino acid patterns (DRY motif and the Y and E conterions) as extant vertebrate species, suggesting that the mechanism for light detection and regulation is similar to rhabdomeric rhodopsins. Both OPN4m and OPN4x paralogs are found …

How The Leopard Hides Its Spots: Asip Mutations And Melanism In Wild Cats, Alexsandra Schneider, Victor A. David, Warren E. Johnson, Stephen J. O'Brien, Gregory S. Barsh, Marilyn Menotti-Raymond, Eduardo Eizirik

Biology Faculty Articles

The occurrence of melanism (darkening of the background coloration) is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus) is a particularly important target for research, given the iconic status of the ‘black panther’ and the extremely …

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 …

A Postulate For Tiger Recovery: The Case Of The Caspian Tiger, Carlos A. Driscoll, I. Chestin, H. Jungius, O. Pereladova, Y. Darman, E, Dinerstein, J. Seidensticker, J. Sanderson, S. Christie, Shu-Jin Luo, S. Shrestha, Y. Zhuravlev, Olga Uphyrkina, Y. V. Jhala, S. P. Yadav, D. G. Pikunov, Nobuyuki Yamaguchi, David E. Wildt, J. L. D. Smith, L. Marker, P. J. Nyhus, R. Tilson, David W. Macdonald, Stephen J. O'Brien

Biology Faculty Articles

Recent genetic analysis has shown that the extinct Caspian Tiger (P. t. virgata) and the living Amur Tigers (P. t. altaica) of the Russian Far East are actually taxonomically synonymous and that Caspian and Amur groups historically formed a single population, only becoming separated within the last 200 years by human agency. A major conservation implication of this finding is that tigers of Amur stock might be reintroduced, not only back into the Koreas and China as is now proposed, but also through vast areas of Central Asia where the Caspian tiger once lived. However, under the current tiger conservation …

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 …

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

Biology Faculty Articles

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

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

Biology Faculty Articles

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

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

Biology Faculty Articles

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

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

Biology Faculty Articles

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

Adaptive Evolution Of The Matrix Extracellular Phosphoglycoprotein In Mammals, Joao P. Machado, Warren E. Johnson, Stephen J. O'Brien, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

Background

Matrix extracellular phosphoglycoprotein (MEPE) belongs to a family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs) that play a key role in skeleton development, particularly in mineralization, phosphate regulation and osteogenesis. MEPE associated disorders cause various physiological effects, such as loss of bone mass, tumors and disruption of renal function (hypophosphatemia). The study of this developmental gene from an evolutionary perspective could provide valuable insights on the adaptive diversification of morphological phenotypes in vertebrates.

Results

Here we studied the adaptive evolution of the MEPE gene in 26 Eutherian mammals and three birds. The comparative genomic analyses revealed a high degree …

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 …

A Molecular Phylogeny Of Living Primates, Polina L. Perelman, Warren E. Johnson, Christian Roos, Hector Seuanez, Julie E. Horvath, Miguel A. M. Moreira, Bailey Kessing, J. U. Pontius, Melody E. Roelke, Yves Rumpler, Maria P. C. Schneider, Artur Silva, Stephen J. O'Brien, Jill Pecon-Slattery

Biology Faculty Articles

Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate …

Genome-Wide Characterization Of Centromeric Satellites From Multiple Mammalian Genomes, Can Alkan, Maria Francesca Cardone, Claudia Rita Catacchio, Francesca Antonacci, Stephen J. O'Brien, Oliver A. Ryder, Stefania Purgato, Monica Zoli, Evan E. Eichler, Mario Ventura

Biology Faculty Articles

Despite its importance in cell biology and evolution, the centromere has remained the final frontier in genome assembly and annotation due to its complex repeat structure. However, isolation and characterization of the centromeric repeats from newly sequenced species are necessary for a complete understanding of genome evolution and function. In recent years, various genomes have been sequenced, but the characterization of the corresponding centromeric DNA has lagged behind. Here, we present a computational method (RepeatNet) to systematically identify higher-order repeat structures from unassembled whole-genome shotgun sequence and test whether these sequence elements correspond to functional centromeric sequences. We analyzed genome …

Genetic Introgression And The Survival Of Florida Panther Kittens, Jeffrey A. Hostetler, David P. Onorato, James D. Nichols, Warren E. Johnson, Melody E. Roelke, Stephen J. O'Brien, Deborah Jansen, Madan K. Oli

Biology Faculty Articles

Estimates of survival for the young of a species are critical for population models. These models can often be improved by determining the effects of management actions and population abundance on this demographic parameter. We used multiple sources of data collected during 1982–2008 and a live-recapture dead-recovery modeling framework to estimate and model survival of Florida panther (Puma concolor coryi) kittens (age 0–1 year). Overall, annual survival of Florida panther kittens was 0.323 ± 0.071 (SE), which was lower than estimates used in previous population models. In 1995, female pumas from Texas (P. c. stanleyana) were …

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 …

Light Whole Genome Sequence For Snp Discovery Across Domestic Cat Breeds, James C. Mullikin, Nancy F. Hansen, Lei Shen, Heather Ebling, William F. Donahue, Wei Tao, David J. Saranga, Adrianne Brand, Marc J. Rubenfield, Alice C. Young, Pedro Cruz, Carlos Driscoll, Victor David, Samer W. K. Al-Murrani, Mary F. Locniskar, Mitchell S. Abrahamsen, Stephen J. O'Brien, Douglas R. Smith, Jeffrey A. Brockman

Biology Faculty Articles

Background

The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus -- FeLV, feline coronavirus -- FECV, feline immunodeficiency virus - FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery.

Description

To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the …