Genetics and Genomics Commons^™

Untangling The Placentome Gene Network Of Beef Heifers In Early Gestation, Wellison J.S. Diniz, Lawrence P. Reynolds, Alison K. Ward, Pawel P. Borowicz, Kevin K. Sedivec, Kacie L. Mccarthy, Cierrah J. Kassetas, Friederike Baumgaertner, James D. Kirsch, Sheri T. Dorsam, Tammi L. Neville, J. Chris Forcherio, Ronald R. Scott, Joel S. Caton, Carl R. Dahlen

Department of Animal Science: Faculty Publications

The cotyledon and caruncle tissues provide a functional bridge between the fetus and the dam. However, the relationship between these tissues and the transcriptomic profile that underlies the tissue functions remains elusive. Herein we investigate the expression profile of cotyledon and caruncle from nulliparous beef heifers carrying female fetuses at day 83 of pregnancy to identify changes occurring across tissues that contribute to placental function and their tissue-specific roles. We identified 2654 differentially expressed genes [padj ≤ 0.05, abs(log2FC) ≥ 1], including nutrient transporters and paternally imprinted genes. We found key regulators of tissue function and differentiation, including FOXO4, GATA2, …

Determining Some Quality Properties Of Oat Genotypes Collected From The Middle And West Black Sea Region, Zeki Mut, Hasan Akay, Ozge Doganay Erbas Kose, Ismail Sezer

The Philippine Agricultural Scientist

Healthy foodstuffs, including functional foods, are the key component of a healthy and prosperous life. Oat grains are rich in protein, soluble dietary fiber, β-glucan, starch, oil, some vitamins and minerals, and thus accepted as a healthy foodstuff. This study was conducted to determine physical and chemical quality traits of many different oat landraces/cultivars. In this study, 251 local oat genotypes, collected from 10 provinces of Western and Middle Black Sea Regions of Turkey and four standard oat cultivars were grown over the experimental fields of the Agricultural Application and Research Center at Samsun Ondokuz Mayıs University for two years …

Phylogenetic Analysis Of Tilapia Lake Virus (Tilv) Isolates From The Philippines Based On Partial Genome Segment 3 Sequences [Research Note], Dan Joseph C. Logronio, Joselito R. Somga, Maria Rowena R. Romana-Eguia, Sonia Somga, Demy Catedral, Gonzalo Jr Coloma

The Philippine Agricultural Scientist

This study aimed to expand current knowledge on TiLV genetic diversity by sequence analysis of a portion of genome segment 3 of TiLV detected from the Philippines. This includes a recently deposited sequence in GenBank (Accession No. LC504279) and six new sequences from cases of infection reported from 2017 to 2020. Phylogenetic analysis of 179 bp fragment of segment 3 showed that the seven TiLV isolates from the Philippines can be divided into three phylogenetic groups. When comparing all sequences, unique nucleotide substitutions and amino acids were noted among these groups. Variation in mortality rates in naturally infected samples was …

Large-Scale Integrative Analysis Of Soybean Transcriptome Using An Unsupervised Autoencoder Model, Lingtao Su, Chunhui Xu, Shuai Zeng, Li Su, Trupti Joshi, Gary Stacey, Dong Xu

Biomedical Sciences

Plant tissues are distinguished by their gene expression patterns, which can help identify tissue-specific highly expressed genes and their differential functional modules. For this purpose, large-scale soybean transcriptome samples were collected and processed starting from raw sequencing reads in a uniform analysis pipeline. To address the gene expression heterogeneity in different tissues, we utilized an adversarial deconfounding autoencoder (AD-AE) model to map gene expressions into a latent space and adapted a standard unsupervised autoencoder (AE) model to help effectively extract meaningful biological signals from the noisy data. As a result, four groups of 1,743, 914, 2,107, and 1,451 genes were …

Elucidating The Clinical Spectrum And Molecular Basis Of Hyal2 Deficiency, Emily G Farrow, Dihong Zhou, Rick Hemming, Kenneth Zahka, Barry A Chioza, Lettie E Rawlins, Olivia K Wenger, Adam C Gunning, Simone Pizzi, Roberta Onesimo, Giuseppe Zampino, Emily Barker, Natasha Osawa, Megan Christine Rodriguez, Teresa M Neuhann, Elaine H Zackai, Beth Keena, Jenina Capasso, Elizabeth Bhoj, Dong Li, Hakon Hakonarson, Ingrid M Wentzensen, Adam Jackson, Kate E Chandler, Zeynep H Coban-Akdemir, Jennifer E Posey, Siddharth Banka, James R Lupski, Sarah E Sheppard, Marco Tartaglia, Barbara Triggs-Raine, Andrew H Crosby, Emma L Baple

Faculty, Staff and Student Publications

PURPOSE: We previously defined biallelic HYAL2 variants causing a novel disorder in 2 families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular abnormalities, with Hyal2 knockout mice displaying similar phenotypes. In this study, we better define the phenotype and pathologic disease mechanism.

METHODS: Clinical and genomic investigations were undertaken alongside molecular studies, including immunoblotting and immunofluorescence analyses of variant/wild-type human HYAL2 expressed in mouse fibroblasts, and in silico modeling of putative pathogenic variants.

RESULTS: Ten newly identified individuals with this condition were investigated, and they were associated with 9 novel pathogenic variants. Clinical studies defined genotype-phenotype correlations and …

The Clock Modulator Nobiletin Mitigates Astrogliosis-Associated Neuroinflammation And Disease Hallmarks In An Alzheimer’S Disease Model, Ruben Gomez-Gutierrez, Kazunari Nohara, Gabriel Escobedo, Jong Min Choi, Chorong Han, Kazuhiro Yagita, Sung Yun Jung, Claudio Soto, Hyun Kyoung Lee, Rodrigo Morales, Seung-Hee Yoo, Zheng Chen

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, and there is a pressing need to identify disease-modifying factors and devise interventional strategies. The circadian clock, our intrinsic biological timer, orchestrates various cellular and physiological processes including gene expression, sleep, and neuroinflammation; conversely, circadian dysfunctions are closely associated with and/or contribute to AD hallmarks. We previously reported that the natural compound Nobiletin (NOB) is a clock-enhancing modulator that promotes physiological health and healthy aging. In the current study, we treated the double transgenic AD model mice, APP/PS1, with NOB-containing diets. NOB significantly alleviated β-amyloid burden in both the hippocampus and the …

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 …

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. …

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 …

Genetic Errors Of Immunity Distinguish Pediatric Nonmalignant Lymphoproliferative Disorders, Nmazuo W Ozuah, 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, 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 …