Genetics and Genomics Commons^™

A Tale Of Two Theories: Using An Engineered Strain Of E. Coli To Bridge The Gap Between Quorum Sensing And Diffusion Sensing, Cortney E. Wilson

HCNSO Student Theses and Dissertations

Cooperation is a trait that is found at all levels of biological organization. Interestingly, cooperation appears to occur in bacteria that produce small, easily diffusible molecules called autoinducers. To understand why bacteria produce these autoinducers, the scientific community has focused on one predominant theory called quorum sensing. Under this theory, bacteria produce autoinducers so they can sense the density of the population. Once a sufficiently high population density is reached, autoinducers initiate the production of a costly gene product that serves to benefit the population. In contrast, a competing theory called diffusion sensing suggests that autoinducers are used by the …

Chromosomal-Level Assembly Of The Asian Seabass Genome Using Long Sequence Reads And Multi-Layered Scaffolding, Shubha Vij, Heiner Kuhl, Inna S. Kuznetsova, Aleksey Komissarov, Andrey A. Yurchenko, Peter Van Heusden, Siddharth Singh, Natascha May Thevasagayam, Sai Rama Sridatta Prakki, Kathiresan Purushothaman, Jolly M. Saju, Junhui Jiang, Stanley Kimbung Mbandi, Mario Jonas, Amy Hin Yan Tong, Sarah Mwangi, Doreen Lau, Si Yan Ngoh, Woei Chang Liew, Xueyan Shen, Lawrence S. Hon, James P. Drake, Matthew Boitano, Richard Hall, Chen-Shan Chin, Ramkumar Lachumanan, Jonas Korlach, Vladimir Trifonov, Marsel Kabilov, Alexey Tupikin, Darrell Green, Simon Moxon, Tyler Garvin, Fritz J. Sedlazeck, Gregory W. Vurture, Gopikrishna Gopalapillai, Vinaya Kumar Katneni, Tansyn H. Noble, Vinod Scaria, Sridhar Sivasubbu, Dean R. Jerry, Stephen J. O'Brien, Michael C. Schatz, Tamas Dalmay, Stephen W. Turner, Si Lok, Alan Christoffels, Laszlo Orban

Biology Faculty Articles

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species’ native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications …

The Population Origins And Expansion Of Feral Cats In Australia, Peter B.S. Spencer, Andrey A. Yurchenko, Victor A. David, Rachael Scott, Klaus Peter Koepfli, Carlos Driscoll, Stephen J. O'Brien, Marilyn Menotti-Raymond

Biology Faculty Articles

The historical literature suggests that in Australia, the domestic cat (Felis catus) had a European origin [~200 years before present (ybp)], but it is unclear if cats arrived from across the Asian land bridge contemporaneously with the dingo (4000 ybp), or perhaps immigrated ~40000 ybp in association with Aboriginal settlement from Asia. The origin of cats in Australia is important because the continent has a complex and ancient faunal assemblage that is dominated by endemic rodents and marsupials and lacks the large placental carnivores found on other large continents. Cats are now ubiquitous across the entire Australian continent and have …

Genomic Legacy Of The African Cheetah, Acinonyx Jubatus, Pavel Dobrynin, Shiping Liu, Gaik Tamazian, Zijun Xiong, Andrey A. Yurchenko, Ksenia Krasheninnikova, Sergey Kliver, A. Schmidt-Kunzel, Klaus-Peter Koepfli, Warren E. Johnson, Lukas F. K. Kuderna, Raquel Garcia-Perez, Marc De Manuel, Ricardo Godinez, Aleksey Komissarov, Alexey Makunin, Vladimir Brukhin, Weilin Qiu, Long Zhou, Fang Li, Jian Yi, Carlos A. Driscoll, Agostinho Antunes, T. K. Oleksyk, Eduardo Eizirik, Polina Perelman, Melody E. Roelke, David E. Wildt, Mark Diekhans, Tomas Marques-Bonet, Laurie Marker, Jong Bhak, Jun Wang, Guojie Zhang, Stephen J. O'Brien

Biology Faculty Articles

Background

Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations.

Results

Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years …

Intrinsic Challenges In Ancient Microbiome Reconstruction Using 16s Rrna Gene Amplification, Kirsten Ziesemer, Allison Mann, Krithivasan Sankaranarayanan, Hannes Schroeder, Andrew T. Ozga, Bernd W. Brandt, Egija Zaura, Andrea Waters-Rist, Menno Hoogland, Domingo C. Salazar-Garcia, Mark Aldenderfer, Camilla Speller, Jessica Hendy, Darlene A. Weston, Sandy J. Macdonald, Gavin H. Thomas, Matthew J. Collins, Cecil M. Lewis Jr., Corinne Hofman, Christina Warinner

Biology Faculty Articles

To date, characterization of ancient oral (dental calculus) and gut (coprolite) microbiota has been primarily accomplished through a metataxonomic approach involving targeted amplification of one or more variable regions in the 16S rRNA gene. Specifically, the V3 region (E. coli341–534) of this gene has been suggested as an excellent candidate for ancient DNA amplification and microbial community reconstruction. However, in practice this metataxonomic approach often produces highly skewed taxonomic frequency data. In this study, we use non-targeted (shotgun metagenomics) sequencing methods to better understand skewed microbial profiles observed in four ancient dental calculus specimens previously analyzed by amplicon …

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.

The First Whole Genome And Transcriptome Of The Cinereous Vulture Reveals Adaptation In The Gastric And Immune Defense Systems And Possible Convergent Evolution Between The Old And New World Vultures, Oksung Chung, Seondeok Jin, Yun Sung Cho, Jeongheui Lim, Hyunho Kim, Sungwoong Jho, Hak-Min Kim, Jehoon Jun, Hyejin Lee, Alvin Chon, Junsu Ko, Jeremy Edwards, Jessica A. Weber, Kyudong Han, Stephen J. O'Brien, Andrea Manica, Jong Bhak, Woon Kee Paek

Biology Faculty Articles

Background: The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functionally selected genetic variants. Furthermore, the presence of two independently evolved vulture groups, Old World and New World vultures, provides a natural experiment in which to investigate convergent evolution due to obligate scavenging.

Results: We sequenced the genome of a cinereous vulture, and mapped it to the bald …

Gene Loss, Adaptive Evolution And The Co-Evolution Of Plumage Coloration Genes With Opsins In Birds, Rui Borges, Imran Khan, Warren E. Johnson, M. Thomas P. Gilbert, Guojie Zhang, Erich D. Jarvis, Stephen J. O'Brien, Agostinho Antunes

Biology Faculty Articles

Background: The wide range of complex photic systems observed in birds exemplifies one of their key evolutionary adaptions, a well-developed visual system. However, genomic approaches have yet to be used to disentangle the evolutionary mechanisms that govern evolution of avian visual systems.

Results: We performed comparative genomic analyses across 48 avian genomes that span extant bird phylogenetic diversity to assess evolutionary changes in the 17 representatives of the opsin gene family and five plumage coloration genes. Our analyses suggest modern birds have maintained a repertoire of up to 15 opsins. Synteny analyses indicate that PARA and PARIE pineal …

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, …

Origins Of An Unmarked Georgia Cemetery Using Ancient Dna Analysis, Andrew T. Ozga, Raul Y. Tito, Brian M. Kemp, Hugh Matternes, Alexandra J. Obregon-Tito, Leslie Neal, Cecil M. Lewis Jr.

Biology Faculty Articles

Determining the origins of those buried within undocumented cemeteries is of incredible importance to historical archaeologists and, in many cases, the nearby communities. In the case of Avondale Burial Place, a cemetery in Bibb County, Georgia, in use from 1820 to 1950, all written documentation of those interred within it has been lost. Osteological and archaeological evidence alone could not describe, with confidence, the ancestral origins of the 101 individuals buried there. In the present study, we used ancient DNA extraction methods in well-preserved skeletal fragments from 20 individuals buried in Avondale Burial Place to investigate the origins of the …

Dynamics Of Marine Bacterial Community Diversity Of The Coastal Waters Of The Reefs, Inlets, And Wastewater Outfalls Of Southeast Florida, Alexandra Mandina Campbell, Jay Fleisher, Christopher D. Sinigalliano, James R. White, Jose V. Lopez

Marine & Environmental Sciences Faculty Articles

Coastal waters adjacent to populated southeast Florida possess different habitats (reefs, oceanic inlets, sewage outfalls) that may affect the composition of their inherent microbiomes. To determine variation according to site, season, and depth, over the course of 1 year, we characterized the bacterioplankton communities within 38 nearshore seawater samples derived from the Florida Area Coastal Environment (FACE) water quality survey. Six distinct coastal locales were profiled – the Port Everglades and Hillsboro Inlets, Hollywood and Broward wastewater outfalls, and associated reef sites using culture-independent, high-throughput pyrosequencing of the 16S rRNA V4 region. More than 227,000 sequences helped describe longitudinal taxonomic …

Recurrent Evolution Of Melanism In South American Felids, Alexsandra Schneider, Corneliu Henegar, Kenneth Day, Devin Absher, Constanza Napolitano, Leandro Silveira, Victor A. David, Stephen J. O'Brien, Marilyn Menotti-Raymond, Gregory S. Barsh, Eduardo Eizirik

Biology Faculty Articles

Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP) or the Melanocortin 1 receptor (MC1R) as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo), the kodkod (Leopardus guigna), and Geoffroy’s cat …

Smilefinder: A Resampling-Based Approach To Evaluate Signatures Of Selection From Genome-Wide Sets Of Matching Allele Frequency Data In Two Or More Diploid Populations, Wilfred M. Guiblet, Kai Zhao, Stephen J. O'Brien, Steven E. Massey, Alfred L. Roca, T. K. Oleksyk

Biology Faculty Articles

Background: Adaptive alleles may rise in frequency as a consequence of positive selection, creating a pattern of decreased variation in the neighboring loci, known as a selective sweep. When the region containing this pattern is compared to another population with no history of selection, a rise in variance of allele frequencies between populations is observed. One challenge presented by large genome-wide datasets is the ability to differentiate between patterns that are remnants of natural selection from those expected to arise at random and/or as a consequence of selectively neutral demographic forces acting in the population.

Findings: SmileFinder is …

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we …

Comparative Population Genetics And Evolutionary History Of Two Commonly Misidentified Billfishes Of Management And Conservation Concern, Andrea M. Bernard, Mahmood S. Shivji, Eric Prince, Fabio H.V. Hazin, Freddy Arocha, Andres Domingo, Kevin A. Feldheim

Marine & Environmental Sciences Faculty Articles

Background:  Misidentifications between exploited species may lead to inaccuracies in population assessments, with potentially irreversible conservation ramifications if overexploitation of either species is occurring. A notable showcase is provided by the realization that the roundscale spearfish (Tetrapturus georgii), a recently validated species, has been historically misidentified as the morphologically very similar and severely overfished white marlin (Kajikia albida) (IUCN listing: Vulnerable). In effect, no information exists on the population status and evolutionary history of the enigmatic roundscale spearfish, a large, highly vagile and broadly distributed pelagic species. We provide the first population genetic evaluation of the …

The Birds Of Genome10k, Stephen J. O'Brien, David Haussler, Oliver A. Ryder

Biology Faculty Articles

Everyone loves the birds of the world. From their haunting songs and majesty of flight to dazzling plumage and mating rituals, bird watchers – both amateurs and professionals - have marveled for centuries at their considerable adaptations. Now, we are offered a special treat with the publication of a series of papers in dedicated issues of Science, Genome Biology and GigaScience (which also included pre-publication data release). These present the successful beginnings of an international interdisciplinary venture, the Avian Phylogenomics Project that lets us view, through a genomics lens, modern bird species and the evolutionary events that produced them.

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 …

Mammalian Keratin Associated Proteins (Krtaps) Subgenomes: Disentangling Hair Diversity And Adaptation To Terrestrial And Aquatic Environments, Imran Khan, Emanuel Maldonado, Vitor Vasconcelos, Stephen J. O'Brien, Warren E. Johnson, Agostinho Antunes

Marine & Environmental Sciences Faculty Articles

Background: Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation.

Results: We exhaustively characterized the KRTAP gene family in 22 mammalian genomes, confirming the existence of 30 KRTAP subfamilies evolving at different rates with varying degrees of diversification and homogenization. Within the two major classes of KRTAPs, the high cysteine (HS) subfamily experienced strong concerted evolution, high rates of gene conversion/recombination and high GC content. In contrast, high glycine-tyrosine …

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 …

Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels And Status Of Regional Lymph Nodes In Patients With Sporadic Colorectal Cancer From Southern China, Yu Liang, Weizhong Tang, Tiquiang Huang, Yong Gao, Aihua Tan, Xiaobo Yang, Haiying Zhang, Yanling Hu, Xue Qin, Shan Li, Shijun Zhang, Linjian Mo, Zhenjia Liang, Deyi Shi, Zhang Huang, Yingyong Guan, Jicheng Zhou, Cheryl Winkler, Stephen J. O'Brien, Jianfeng Xu, Zengnan Mo, Tao Peng

Marine & Environmental Sciences Faculty Articles

Background:  Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications.

Methods and Findings:  Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI …

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 …

Personal Genomics: Good, Evil, Or Both?, Emily Schmitt

CAHSS Intellectual Conversations

With the increasing availability of personal genomic testing, there have been warnings that the results may lead to discrimination by insurance companies, employers, or the community. In addition, some individuals fear potential identity theft and loss of personal autonomy, despite the benefits of discovering potential genetic risks and possibilities of more-focused treatments. This lecture will examine whether personal genomics is good, evil, or both.

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 …