Genetics and Genomics Commons^™

Carbapenemase-Producing Pseudomonas Aeruginosa – An Emerging Challenge, Fred C. Tenover, David P. Nicolau, Christian M. Gill

Biology Faculty Publications

Carbapenem-resistant Pseudomonas aeruginosa (CR-PA) is a major healthcare-associated pathogen worldwide. In the United States, 10–30% of P. aeruginosa isolates are carbapenem-resistant, while globally the percentage varies considerably. A subset of carbapenem-resistant P. aeruginosa isolates harbour carbapenemases, although due in part to limited screening for these enzymes in clinical laboratories, the actual percentage is unknown. Carbapenemase-mediated carbapenem resistance in P. aeruginosa is a significant concern as it greatly limits the choice of anti-infective strategies, although detecting carbapenemase-producing P. aeruginosa in the clinical laboratory can be challenging. Such organisms also have been associated with nosocomial spread requiring infection prevention interventions. The carbapenemases …

Identifying Molecular Markers For Early Detection Of Toxic Cyanobacteria And Dinoflagellate, Shafqat F. Ehsan

Honors Program Theses and Research Projects

Harmful algal Blooms (HABs) develop when algal colonies grow out of control, causing toxicity or injury to humans, fish, shellfish, marine mammals, and birds. Most HABs of public health concern in saltwater generally are caused by eukaryotic dinoflagellates and diatoms. Prokaryotic cyanobacteria are usually responsible for freshwater blooms although they can contribute to saltwater and brackish blooms too. A common monitoring target of both groups is the saxitoxin-encoding genes. Saxitoxin(STX) is responsible for Paralytic shellfish poisoning, a foodborne illness developed from consumption of STX contaminated shellfish. Each cyanobacterial SXT gene cluster contains a set of core genes, common to all …

Rare Coding Variants In Rcn3 Are Associated With Blood Pressure, Karen Y. He, Tanika N. Kelly, Heming Wang, Jingjing Liang, Luke Zhu, Brian E. Cade, Themistocles L. Assimes, Lewis C. Becker, Amber L. Beitelshees, Lawrence F. Bielak, Adam P. Bress, Jennifer A. Brody, Yen-Pei Christy Chang, Yi-Cheng Chang, Paul S. De Vries, Ravindranath Duggirala, Ervin R. Fox, Nora Franceschini, Anna L. Furniss, Yan Gao, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of …

The Antarctic Weddell Seal Genome Reveals Evidence Of Selection On Cardiovascular Phenotype And Lipid Handling, Hyun Ji Noh, Jason Turner-Maier, S. Anne Schulberg, Michael L. Fitzgerald, Jeremy Johnson, Kaitlin N. Allen, Luis A. Huckstadt, Annabelle J. Batten, Jessica Alfoldi, Daniel P. Costa, Elinor K. Karlsson, Warren M. Zapol, Emmanuel S. Buys, Kerstin Lindbald-Toh, Allyson G. Hindle

Life Sciences Faculty Research

The Weddell seal (Leptonychotes weddellii) thrives in its extreme Antarctic environment. We generated the Weddell seal genome assembly and a high-quality annotation to investigate genome-wide evolutionary pressures that underlie its phenotype and to study genes implicated in hypoxia tolerance and a lipid-based metabolism. Genome-wide analyses included gene family expansion/contraction, positive selection, and diverged sequence (acceleration) compared to other placental mammals, identifying selection in coding and non-coding sequence in five pathways that may shape cardiovascular phenotype. Lipid metabolism as well as hypoxia genes contained more accelerated regions in the Weddell seal compared to genomic background. Top-significant genes were SUMO2 and EP300; …

Phylogenomic Discordance Suggests Polytomies Along The Backbone Of The Large Genus Solanum, Edeline Gagnon, Rebeccca Hilgenhof, Andrés Orejuela, Angela J. Mcdonnell, Gaurav Sablok, Xavier Aubriot, Leandro Giacomin, Yuri Gouvêa, Thamyris Bragionis, João Renato Stehmann, Lynn Bohs, Steven Dodsworth, Christopher T. Martine, Péter Poczai, Sandra Knapp, Tiina Särkinen

Faculty Journal Articles

Premise of the study

Evolutionary studies require solid phylogenetic frameworks, but increased volumes of phylogenomic data have revealed incongruent topologies among gene trees in many organisms both between and within genomes. Some of these incongruences indicate polytomies that may remain impossible to resolve. Here we investigate the degree of gene-tree discordance in Solanum, one of the largest flowering plant genera that includes the cultivated potato, tomato, and eggplant, as well as 24 minor crop plants.

Methods

A densely sampled species-level phylogeny of Solanum is built using unpublished and publicly available Sanger sequences comprising 60% of all accepted species (742 spp.) …

Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi

Plant Pathology Faculty Publications

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG …

Long-Read Sequencing Of The Zebrafish Genome Reorganizes Genomic Architecture, Yelena Chernyavskaya, Xiaofei Zhang, Jinze Liu, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Nanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers.

RESULTS: We used long-read nanopore sequencing to generate a de novo assembly of the zebrafish genome and compared our assembly to the current reference genome, GRCz11. The new assembly identified 1697 novel insertions and deletions over one kilobase in length and placed …

Detection Of Methicillin-Resistant Staphylococcus Aureus Infections Using Molecular Methods, Fred C. Tenover, Isabella A. Tickler

Biology Faculty Publications

The application of molecular detection methods for bacterial pathogens has dramatically improved the outcomes of septic patients, including those with methicillin-resistant Staphylococcus aureus (MRSA) infections. Molecular methods can be applied to a variety of clinical specimens including nasal swabs, growth in blood culture bottles, and wounds. While data show that the overall accuracy of molecular tests for MRSA is high, results can be confounded by the presence of multiple staphylococcal species in a specimen, insertions and deletions of DNA in and around the Staphylococcal Cassette Chromosome mec (SCCmec) element, and point mutations in mecA. Herein, we explore the complexities of …

Apoe Genetics Influence Murine Gut Microbiome, Diana J. Zajac, Stefan J. Green, Lance A. Johnson, Steven Estus

Physiology Faculty Publications

Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we evaluated effects of APOE heterozygosity and tested whether these overall results extended to mice maintained under ideal conditions for microbiome analyses. To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, homozygous APOE3 mice were crossed to homozygous APOE2 or homozygous APOE4 mice prior to the study, and the resulting …

Conservation, Comparative Genomics And Species Delimitation Of The Reindeer Lichens (Cladonia), Jordan R. Hoffman

Dissertations, Theses, and Capstone Projects

The genus Cladonia represents one of the most speciose genera of lichenized fungi, with more than 500 known species encompassing a diverse array of morphologies and habits. These lichens form keystone species in many habitats, serving a variety of ecological roles. However, despite being among of the more well studied lichens, there is much still unknown or under-studied about them. As is the case with most lichen study systems, phylogenetic study has been limited to a small number of partial loci, while adoption of next-generation sequence methods has been slow. As a consequence, there are still knowledge gaps in Cladonia …

Identifying Gene Network Patterns And Associated Cellular Immune Responses In Children With Or Without Nut Allergy, Khui Hung Lee, Anthony Bosco, Michael O'Sullivan, Yong Song, Jessica Metcalfe, Kan Yu, Benjamin J. Mullins, Richard Loh, Guicheng Zhang

Research outputs 2022 to 2026

Background: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. Methods: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

Genetic Errors Of Immunity Distinguish Pediatric Nonmalignant Lymphoproliferative Disorders, Lisa R Forbes, Olive S Eckstein, Nitya Gulati, Erin C Peckham-Gregory, Nmazuo W Ozuah, Joseph Lubega, Nader K El-Mallawany, Jennifer E Agrusa, M Cecilia Poli, Tiphanie P Vogel, Natalia S Chaimowitz, Nicholas L Rider, Emily M Mace, Jordan S Orange, Jason W Caldwell, Juan C Aldave-Becerra, Stephen Jolles, Francesco Saettini, Hey J Chong, Asbjorg Stray-Pedersen, Helen E Heslop, Kala Y Kamdar, R Helen Rouce, Donna M Muzny, Shalini N Jhangiani, Richard A Gibbs, Zeynep H Coban-Akdemir, James R Lupski, Kenneth L Mcclain, Carl E Allen, Ivan K Chinn

Faculty, Staff and Student Publications

BACKGROUND: Pediatric nonmalignant lymphoproliferative disorders (PLPDs) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD.

OBJECTIVE: The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes.

METHODS: PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant Epstein-Barr virus (EBV) infection. Fifty-one subjects from …

Extensive Identification Of Genes Involved In Congenital And Structural Heart Disorders And Cardiomyopathy, Nadine Spielmann, Gregor Miller, Tudor I Oprea, Chih-Wei Hsu, Gisela Fobo, Goar Frishman, Corinna Montrone, Hamed Haseli Mashhadi, Jeremy Mason, Violeta Munoz Fuentes, Stefanie Leuchtenberger, Andreas Ruepp, Matias Wagner, Dominik S Westphal, Cordula Wolf, Agnes Görlach, Adrián Sanz-Moreno, Yi-Li Cho, Raffaele Teperino, Stefan Brandmaier, Sapna Sharma, Isabella Rikarda Galter, Manuela A Östereicher, Lilly Zapf, Philipp Mayer-Kuckuk, Jan Rozman, Lydia Teboul, Rosie K A Bunton-Stasyshyn, Heather Cater, Michelle Stewart, Skevoulla Christou, Henrik Westerberg, Amelia M Willett, Janine M Wotton, Willson B Roper, Audrey E Christiansen, Christopher S Ward, Jason D Heaney, Corey L Reynolds, Jan Prochazka, Lynette Bower, David Clary, Mohammed Selloum, Ghina Bou About, Olivia Wendling, Hugues Jacobs, Sophie Leblanc, Hamid Meziane, Tania Sorg, Enrique Audain, Arthur Gilly, Nigel W Rayner, Impc Consortium, Genomics England Research Consortium;, Marc-Phillip Hitz, Eleftheria Zeggini, Eckhard Wolf, Radislav Sedlacek, Steven A Murray, Karen L Svenson, Robert E Braun, Jaqueline K White, Lois Kelsey, Xiang Gao, Toshihiko Shiroishi, Ying Xu, Je Kyung Seong, Fabio Mammano, Glauco P Tocchini-Valentini, Arthur L Beaudet, Terrence F Meehan, Helen Parkinson, Damian Smedley, Ann-Marie Mallon, Sara E Wells, Harald Grallert, Wolfgang Wurst, Susan Marschall, Helmut Fuchs, Steve D M Brown, Ann M Flenniken, Lauryl M J Nutter, Colin Mckerlie, Yann Herault, K C Kent Lloyd, Mary E Dickinson, Valerie Gailus-Durner, Martin Hrabe De Angelis

Faculty, Staff and Students Publications

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, …

Dissecting The Shared Genetic Architecture Of Suicide Attempt, Psychiatric Disorders, And Known Risk Factors, Niamh Mullins, Joo Eun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Ney Alliey Rodriguez

School of Medicine Publications

Background: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. …

Three Complete Mitochondrial Genomes Of Shortfin Mako Sharks, Isurus Oxyrinchus, From The Atlantic And Pacific Oceans, Marissa Mehlrose, Andrea Bernard, Kimberly A. Finnegan, Lauren E. Krausfeldt, Jose V. Lopez, Mahmood Shivji

Biology Faculty Articles

We present complete mitogenome sequences of three shortfin mako sharks (Isurus oxyrinchus) sampled from the western Pacific, and eastern and western Atlantic oceans. Mitogenome sequence lengths ranged between 16,699 bp and 16,702 bp, and all three mitogenomes contained one non-coding control region, two rRNA genes, 22 tRNA genes, and 13 protein-coding genes. Comparative assessment of five mitogenomes from globally distributed shortfin makos (the current three and two previously published mitogenomes) yielded 98.4% identity, with the protein-coding genes ATP8, ATP6, and ND5 as the most variable regions (sequence identities of 96.4%, 96.5%, and 97.6%, respectively). These mitogenome sequences contribute resources …

Knockdown Of Mdm2 In Hepg2 Cell Line: A Step Towards Understanding The Relation Between Mirna590-3p And Its Downstream Target Gene, Mdm2, In Hepatocellular Carcinoma, Jihad Mahmoud

Theses and Dissertations

Background: miRNA 590-3p is a small non-coding RNA that has previously been associated with the occurrence and progression of several cancer types. Its expression pattern and biological role in Hepatocellular carcinoma (HCC), however, remain controversial. Interestingly, a previous study in our lab revealed a tumor suppressing activity of miR-590-3p in HCC and identified the MDM2 gene as the miR-590-3p target gene.

Aim: The current study aimed to knock down the expression of MDM2 in HepG2 cells to understand how the inhibition of MDM2, as a validated downstream target of miR-590-3p, would affect different functional pathways in HCC. In …

Bottom-Up Drivers Of Future Fire Regimes In Western Boreal North America, Adrianna C. Foster, Jacquelyn K. Shuman, Brendan M. Rogers, Xanthe J. Walker, Michelle C. Mack, Laura L. Bourgeau-Chavez, Sander Veraverbeke, Scott J. Goetz

Aspen Bibliography

Forest characteristics, structure, and dynamics within the North American boreal region are heavily influenced by wildfire intensity, severity, and frequency. Increasing temperatures are likely to result in drier conditions and longer fire seasons, potentially leading to more intense and frequent fires. However, an increase in deciduous forest cover is also predicted across the region, potentially decreasing flammability. In this study, we use an individual tree-based forest model to test bottom-up (i.e. fuels) vs top-down (i.e. climate) controls on fire activity and project future forest and wildfire dynamics. The University of Virginia Forest Model Enhanced is an individual tree-based forest model …

A Crispr Toolbox For Generating Intersectional Genetic Mouse Models For Functional, Molecular, And Anatomical Circuit Mapping, Savannah J Lusk, Andrew Mckinney, Patrick J Hunt, Paul G Fahey, Jay Patel, Andersen Chang, Jenny J Sun, Vena K Martinez, Ping Jun Zhu, Jeremy R Egbert, Genevera Allen, Xiaolong Jiang, Benjamin R Arenkiel, Andreas S Tolias, Mauro Costa-Mattioli, Russell S Ray

Faculty, Staff and Students Publications

BACKGROUND: The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of …

Genetic Parameters, Heterosis, And Breed Effects For Body Condition Score And Mature Cow Weight In Beef Cattle, André Mauric F. Ribeiro, Leticia P. Sanglard, Warren M. Snelling, R. Mark Thallman, Larry A. Kuehn, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Understanding the genetic relationship between mature cow weight (MWT) and body condition score (BCS) is useful to implement selection programs focused on cow efficiency. The objectives of this study were to estimate genetic parameters, heterosis, and breed effects for MWT and BCS. In total, 25,035 and 24,522 overlapping records were available for MWT and BCS on 6,138 and 6,131 cows, respectively, from the Germplasm Evaluation program, a crossbred beef population at the U.S. Meat Animal Research Center. Pedigree was available for 48,013 individuals. Univariate animal models were used to estimate heritabilities for each trait by parity. …

The Earth Biogenome Project 2020: Starting The Clock, Harris A. Lewin, Stephen Richards, Erez Lieberman Aiden, Miguel L. Allende, John M. Archibald, Katharine B. Baker, Bridget Baumgartner, Katherine Belov, Giorgio Bertorelle, Mark L. Blaxter, Jing Cai, Nicolette D. Caperello, Keith Carlson, Juan Carlos Castilla-Rubio, Shu-Miaw Chaw, Lei Chen, Anna K. Childers, Jonathan A. Coddington, Dalia A. Conde, Montserrat Corominas, Keith A. Crandall, Andrew J. Crawford, Federica Dipalma, Richard Durbin, Thankgod E. Ebenezer, Scott V. Edwards, Olivier Fedrigo, Paul Flicek, Giulio Formenti, Richard A. Gibbs, M. Thomas P. Gilbert, Melissa M. Goldstein, Jennifer Marshall Graves, Henry T. Greely, Igor V. Grigoriev, Kevin J. Hackett, Neil Hall, David Haussler, Kristofer M. Helgen, Carolyn J. Hogg, Sachiko Isobe, Kjetill Sigurd Jakobson, Axel Janke, Erich D. Jarvis, Warren E. Johnson, Steven J. M. Jones, Elinor K. Karlsson, Paul J. Kersey, Jin-Hyoung Kim, W. John Kress, Shigehiro Kuraku, Mara K. N. Lawniczak, James H. Leebens-Mack, Xueyan Li, Kerstin Lindblad-Toh, Xin Liu, Jose V. Lopez, Tomas Marques-Bonet, Sophie Mazard, Jonna A. K. Mazet, Camila J. Mazzoni, Eugene W. Myers, Rachel J. O'Neill, Sadye Paez, Hyun Park, Gene E. Robinson, Cristina Roquet, Oliver A. Ryder, Jamal S. M. Sabir, H. Bradley Shaffer, Timothy M. Shank, Jacob S. Sherkow, Pamela S. Soltis, Boping Tang, Leho Tedersoo, Marcela Uliano-Silva, Kun Wang, Xiaofeng Wei, Regina Wetzer, Julia L. Wilson, Xun Xu, Huanming Yang, Anne D. Yoder, Guojie Zhang

Biology Faculty Articles

No abstract provided.

Standards Recommendations For The Earth Biogenome Project, Mara K. Lawniczak, Richard Durbin, Paul Flicek, Kerstin Lindblad-Toh, Xiaofeng Wei, John M. Archibald, William J. Baker, Katherine Belov, Mark L. Blaxter, Tomas Marques-Bonet, Anna K. Childers, Jonathan A. Coddington, Keith A. Crandall, Andrew J. Crawford, Robert P. Davey, Federica Di Palma, Qi Fang, Wilfried Haerty, Neil Hall, Katherine J. Hoff, Kerstin Howe, Erich D. Jarvis, Warren E. Johnson, Rebecca N. Johnson, Paul J. Kersey, Xin Liu, Jose V. Lopez, Eugene W. Myers, Olga Vinnere Pettersson, Adam M. Phillippy, Monica F. Poelchau, Kim D. Pruitt, Arang Rhie, Juan Carlos Castilla-Rubio, Sunil Kumar Sahu, Nicholas A. Salmon, Pamela S. Soltis, David Swarbreck, Françoise Thibaud-Nissen, Sibo Wang, Jill L. Wegrzyn, Guojie Zhang, He Zhang, Harris A. Lewin, Stephen Richards

Biology Faculty Articles

A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. …

Why Sequence All Eukaryotes?, Mark Blaxter, John M. Archibald, Anna K. Childers, Jonathan A. Coddington, Keith A. Crandall, Federica Di Palma, Richard Durbin, Scott V. Edwards, Jennifer A.M. Graves, Kevin J. Hackett, Neil Hall, Erich D. Jarvis, Rebecca N. Johnson, Elinor K. Karlsson, W. John Kress, Shigehiro Kuraku, Mara K. N. Lawniczak, Kerstin Lindblad-Toh, Jose V. Lopez, Nancy A. Moran, Gene E. Robinson, Oliver A. Ryder, Beth Shapiro, Pamela S. Soltis, Tandy Warnow, Guojie Zhang, Harris A. Lewin

Biology Faculty Articles

Life on Earth has evolved from initial simplicity to the astounding complexity we experience today. Bacteria and archaea have largely excelled in metabolic diversification, but eukaryotes additionally display abundant morphological innovation. How have these innovations come about and what constraints are there on the origins of novelty and the continuing maintenance of biodiversity on Earth? The history of life and the code for the working parts of cells and systems are written in the genome. The Earth BioGenome Project has proposed that the genomes of all extant, named eukaryotes—about 2 million species—should be sequenced to high quality to produce a …

Data-Driven Modeling Predicts Gene Regulatory Network Dynamics During The Differentiation Of Multipotential Hematopoietic Progenitors, Joanna Handzlik, Manu

Biology Faculty Publications

Cellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) comprising transcription factors (TFs) and the effectors of cytokine signaling. Based largely on analyses conducted at steady state, these GRNs are thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation. Here, we utilize transient gene expression patterns to infer the genetic architecture—the type and strength of regulatory interconnections—and dynamics of a twelve-gene GRN including key TFs and cytokine receptors. We trained gene circuits, dynamical models that learn genetic architecture, on high temporal-resolution gene-expression data from the …

Identifying Conifer Tree Vs. Deciduous Shrub And Tree Regeneration Trajectories In A Space-For-Time Boreal Peatland Fire Chronosequence Using Multispectral Lidar, Humaira Enayetullah, Laura Chasmer, Christopher Hopkinson, Dan Thompson, Danielle Cobbaert

Aspen Bibliography

Wildland fires and anthropogenic disturbances can cause changes in vegetation species composition and structure in boreal peatlands. These could potentially alter regeneration trajectories following severe fire or through cumulative impacts of climate-mediated drying, fire, and/or anthropogenic disturbance. We used lidar-derived point cloud metrics, and site-specific locational attributes to assess trajectories of post-disturbance vegetation regeneration in boreal peatlands south of Fort McMurray, Alberta, Canada using a space-for-time-chronosequence. The objectives were to (a) develop methods to identify conifer trees vs. deciduous shrubs and trees using multi-spectral lidar data, (b) quantify the proportional coverage of shrubs and trees to determine environmental conditions driving …

Chromomap: An R Package For Interactive Visualization Of Multi-Omics Data And Annotation Of Chromosomes, Lakshay Anand, Carlos M. Rodriguez Lopez

Horticulture Faculty Publications

BACKGROUND: The recent advancements in high-throughput sequencing have resulted in the availability of annotated genomes, as well as of multi-omics data for many living organisms. This has increased the need for graphic tools that allow the concurrent visualization of genomes and feature-associated multi-omics data on single publication-ready plots.

RESULTS: We present chromoMap, an R package, developed for the construction of interactive visualizations of chromosomes/chromosomal regions, mapping of any chromosomal feature with known coordinates (i.e., protein coding genes, transposable elements, non-coding RNAs, microsatellites, etc.), and chromosomal regional characteristics (i.e. genomic feature density, gene expression, DNA methylation, chromatin modifications, etc.) of organisms …

Mutations In Hcfc1 And Ronin Result In An Inborn Error Of Cobalamin Metabolism And Ribosomopathy, Tiffany Chern, Annita Achilleos, Xuefei Tong, Matthew C Hill, Alexander B Saltzman, Lucas C Reineke, Arindam Chaudhury, Swapan K Dasgupta, Yushi Redhead, David Watkins, Joel R Neilson, Perumal Thiagarajan, Jeremy B A Green, Anna Malovannaya, James F Martin, David S Rosenblatt, Ross A Poché

Faculty, Staff and Students Publications

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. However, additional de-regulated genes and the resulting pathophysiology is unknown. Therefore, we have generated mouse models of this disease. In addition to exhibiting loss of Mmachc, metabolic perturbations, and developmental defects previously …

Rare Coding Variants In 35 Genes Associate With Circulating Lipid Levels-A Multi-Ancestry Analysis Of 170,000 Exomes, George Hindy, Peter Dornbos, Mark D Chaffin, Dajiang J Liu, Minxian Wang, Margaret Sunitha Selvaraj, David Zhang, Joseph Park, Carlos A Aguilar-Salinas, Lucinda Antonacci-Fulton, Diego Ardissino, Donna K Arnett, Stella Aslibekyan, Gil Atzmon, Christie M Ballantyne, Francisco Barajas-Olmos, Nir Barzilai, Lewis C Becker, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Lori L Bonnycastle, Erwin Bottinger, Donald W Bowden, Matthew J Bown, Jennifer A Brody, Jai G Broome, Noël P Burtt, Brian E Cade, Federico Centeno-Cruz, Edmund Chan, Yi-Cheng Chang, Yii-Der I Chen, Ching-Yu Cheng, Won Jung Choi, Rajiv Chowdhury, Cecilia Contreras-Cubas, Emilio J Córdova, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, John Danesh, Paul S De Vries, Ralph A Defronzo, Harsha Doddapaneni, Ravindranath Duggirala, Susan K Dutcher, Patrick T Ellinor, Leslie S Emery, Jose C Florez, Myriam Fornage, Barry I Freedman, Valentin Fuster, Ma Eugenia Garay-Sevilla, Humberto García-Ortiz, Soren Germer, Richard A Gibbs, Christian Gieger, Benjamin Glaser, Clicerio Gonzalez, Maria Elena Gonzalez-Villalpando, Mariaelisa Graff, Sarah E Graham, Niels Grarup, Leif C Groop, Xiuqing Guo, Namrata Gupta, Sohee Han, Craig L Hanis, Torben Hansen, Jiang He, Nancy L Heard-Costa, Yi-Jen Hung, Mi Yeong Hwang, Marguerite R Irvin, Sergio Islas-Andrade, Gail P Jarvik, Hyun Min Kang, Sharon L R Kardia, Tanika Kelly, Eimear E Kenny, Alyna T Khan, Bong-Jo Kim, Ryan W Kim, Young Jin Kim, Heikki A Koistinen, Charles Kooperberg, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Leslie A Lange, Jiwon Lee, Juyoung Lee, Seonwook Lee, Donna M Lehman, Rozenn N Lemaitre, Allan Linneberg, Jianjun Liu, Ruth J F Loos, Steven A Lubitz, Valeriya Lyssenko, Ronald C W Ma, Lisa Warsinger Martin, Angélica Martínez-Hernández, Rasika A Mathias, Stephen T Mcgarvey, Ruth Mcpherson, James B Meigs, Thomas Meitinger, Olle Melander, Elvia Mendoza-Caamal, Ginger A Metcalf, Xuenan Mi, Karen L Mohlke, May E Montasser, Jee-Young Moon, Hortensia Moreno-Macías, Alanna C Morrison, Donna M Muzny, Sarah C Nelson, Peter M Nilsson, Jeffrey R O'Connell, Marju Orho-Melander, Lorena Orozco, Colin N A Palmer, Nicholette D Palmer, Cheol Joo Park, Kyong Soo Park, Oluf Pedersen, Juan M Peralta, Patricia A Peyser, Wendy S Post, Michael Preuss, Bruce M Psaty, Qibin Qi, D C Rao, Susan Redline, Alexander P Reiner, Cristina Revilla-Monsalve, Stephen S Rich, Nilesh Samani, Heribert Schunkert, Claudia Schurmann, Daekwan Seo, Jeong-Sun Seo, Xueling Sim, Rob Sladek, Kerrin S Small, Wing Yee So, Adrienne M Stilp, E Shyong Tai, Claudia H T Tam, Kent D Taylor, Yik Ying Teo, Farook Thameem, Brian Tomlinson, Michael Y Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Teresa Tusié-Luna, Miriam S Udler, Rob M Van Dam, Ramachandran S Vasan, Karine A Viaud Martinez, Fei Fei Wang, Xuzhi Wang, Hugh Watkins, Daniel E Weeks, James G Wilson, Daniel R Witte, Tien-Yin Wong, Lisa R Yanek, Amp-T2d-Genes, Myocardial Infarction Genetics Consortium, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Nhlbi Topmed Lipids Working Group, Sekar Kathiresan, Daniel J Rader, Jerome I Rotter, Michael Boehnke, Mark I Mccarthy, Cristen J Willer, Pradeep Natarajan, Jason A Flannick, Amit V Khera, Gina M Peloso

Faculty, Staff and Student Publications

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, …