Genetics and Genomics Commons^™

Genetic And Non-Genetic Factors Affecting The Expression Of Covid-19-Relevant Genes In The Large Airway Epithelium, Silva Kasela, Victor E Ortega, Molly Martorella, Suresh Garudadri, Jenna Nguyen, Elizabeth Ampleford, Anu Pasanen, Srilaxmi Nerella, Kristina L Buschur, Igor Z Barjaktarevic, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Jeffrey L Curtis, Meilan K Han, Nadia N Hansel, Eric A Hoffman, Robert J Kaner, Jerry A Krishnan, Fernando J Martinez, Merry-Lynn N Mcdonald, Deborah A Meyers, Robert Paine, Stephen P Peters, Mario Castro, Loren C Denlinger, Serpil C Erzurum, John V Fahy, Elliot Israel, Nizar N Jarjour, Bruce D Levy, Xingnan Li, Wendy C Moore, Sally E Wenzel, Charles Langelier, Prescott G Woodruff, Tuuli Lappalainen, Stephanie A Christenson

Faculty, Staff and Student Publications

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.

METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with …

A Novel Jumbo Phage Phima05 Inhibits Harmful Microcystis Sp., Ampapan Naknaen, Oramas Suttinun, Komwit Surachat, Eakalak Khan, Rattanaruji Pomwised

Civil and Environmental Engineering and Construction Faculty Research

Microcystis poses a concern because of its potential contribution to eutrophication and production of microcystins (MCs). Phage treatment has been proposed as a novel biocontrol method for Microcystis. Here, we isolated a lytic cyanophage named PhiMa05 with high efficiency against MCs-producing Microcystis strains. Its burst size was large, with approximately 127 phage particles/infected cell, a short latent period (1 day), and high stability to broad salinity, pH and temperature ranges. The PhiMa05 structure was composed of an icosahedral capsid (100 nm) and tail (120 nm), suggesting that the PhiMa05 belongs to the Myoviridae family. PhiMa05 inhibited both planktonic and aggregated …

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the …

A High-Androgen Microenvironment Inhibits Granulosa Cell Proliferation And Alters Cell Identity, Renee Mcfee Fee, Sarah Romereim, Alexandria P. Snider, Adam F. Summers, William E. Pohlmeier, Scott G. Kurz, Robert A. Cushman, John S. Davis, Jennifer R. Wood, Andrea S. Cupp

Department of Animal Science: Faculty Publications

A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-Müllerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby …

A Whole-Genome Scan For Association With Invasion Success In The Fruit Fly Drosophila Suzukii Using Contrasts Of Allele Frequencies Corrected For Population Structure, Laure Olazcuaga, Anne Loiseau, Hugues Parrinello, Mathilde Paris, Antoine Fraimout, Christelle Guedot, Lauren M. Diepenbrock, Marc Kenis, Jinping Zhang, Xiao Chen, Nicolas Borowiec, Benoit Facon, Heidrun Vogt, Donald K. Price, Heiko Vogel, Benjamin Prud'homme, Arnaud Estoup, Mathieu Gautier

Life Sciences Faculty Research

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic …

Regenerative Rehabilitation And Genomics: Implications For Occupational Therapy, John V. Rider

The Open Journal of Occupational Therapy

The completion of the human genome project has paved the way for health care practitioners to use genetic and environmental information to tailor medical treatment. This innovative approach to health care is rapidly evolving, and occupational therapists need to be aware of the impact it will have on future practice. Regenerative rehabilitation is a product of knowledge and techniques from the fields of rehabilitation and regenerative medicine with the common goal to restore function. Occupational therapists have the potential to play a significant role in regenerative rehabilitation research and implementation. The purpose of this article is to (a) increase understanding …

Zebrafish (Danio Rerio) Hoxb6: An Exploration Into The Divergence Of Genomic Dna Sequence And Gene Expression Across Teleost Fishes Post-Genome Duplication, Amber Lynn Rittgers, Pierre Le Pabic, Adam Davis

Georgia Journal of Science

Hoxb6 is an evolutionarily conserved developmental regulatory gene that functions, in part, to pattern several organs and organ systems within the embryonic trunk during vertebrate embryogenesis. The cis-regulatory circuitry mediating trunk expression in mouse (Mus musculus) may be conserved across gnathostome vertebrates, as several other species show similar trunk expression patterns, including chicken (Gallus gallus), dogfish shark (Scyliorhinus canicula), and several teleost fishes. A whole genome duplication event that occurred in the lineage leading to teleost fishes has generated at least two Hoxb6 genes, hoxb6a and b6b. Two teleost fishes of the …

The Whole Is Greater Than Its Parts: Ensembling Improves Protein Contact Prediction, Wendy M. Billings, Connor J. Morris, Dennis Della Corte

Faculty Publications

The prediction of amino acid contacts from protein sequence is an important problem, as protein contacts are a vital step towards the prediction of folded protein structures. We propose that a powerful concept from deep learning, called ensembling, can increase the accuracy of protein contact predictions by combining the outputs of different neural network models. We show that ensembling the predictions made by different groups at the recent Critical Assessment of Protein Structure Prediction (CASP13) outperforms all individual groups. Further, we show that contacts derived from the distance predictions of three additional deep neural networks—AlphaFold, trRosetta, and ProSPr—can be substantially …

Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. De Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10⁻⁷²), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 …

Widespread Mortality Of Trembling Aspen (Populus Tremuloides) Throughout Interior Alaskan Boreal Forests Resulting From A Novel Canker Disease, Roger W. Ruess, Loretta M. Winton, Gerard C. Adams

Aspen Bibliography

Over the past several decades, growth declines and mortality of trembling aspen throughout western Canada and the United States have been linked to drought, often interacting with outbreaks of insects and fungal pathogens, resulting in a “sudden aspen decline” throughout much of aspen’s range. In 2015, we noticed an aggressive fungal canker causing widespread mortality of aspen throughout interior Alaska and initiated a study to quantify potential drivers for the incidence, virulence, and distribution of the disease. Stand-level infection rates among 88 study sites distributed across 6 Alaska ecoregions ranged from < 1 to 69%, with the proportion of trees with canker that were dead averaging 70% across all sites. The disease is most prevalent north of the Alaska Range within the Tanana Kuskokwim ecoregion. Modeling canker probability as a function of ecoregion, stand structure, landscape position, and climate revealed that smaller-diameter trees in older stands with greater aspen basal area have the highest canker incidence and mortality, while younger trees in younger stands appear virtually immune to the disease. Sites with higher summer vapor pressure deficits had significantly higher levels of canker infection and mortality. We believe the combined effects of this novel fungal canker pathogen, drought, and the persistent aspen leaf miner outbreak are triggering feedbacks between carbon starvation and hydraulic failure that are ultimately driving widespread mortality. Warmer early-season temperatures and prolonged late summer drought are leading to larger and more severe wildfires throughout interior Alaska that are favoring a shift from black spruce to forests dominated by Alaska paper birch and aspen. Widespread aspen mortality fostered by this rapidly spreading pathogen has significant implications for successional dynamics, ecosystem function, and feedbacks to disturbance regimes, particularly on sites too dry for Alaska paper birch.

Historic Declines In Growth Portend Trembling Aspen Death During A Contemporary Leaf Miner Outbreak In Alaska, Melissa A. Boyd, Logan T. Berner, Adrianna C. Foster, Scott J. Goetz, Brendan M. Rogers, Xanthe J. Walker, Michelle C. Mack

Aspen Bibliography

Climate change-driven droughts and insect outbreaks are becoming more frequent and widespread, increasing forest vulnerability to mortality. By addressing the impacts of climate and insects on tree growth preceding death, we can better understand tree mortality risk under a changing climate. Here, we used tree stature and interannual growth (basal area increment; BAI) to assess processes leading to trembling aspen (Populus tremuloides) survival or mortality during an unprecedented leaf miner (Phyllocnistis populiella) outbreak in boreal North America. We identified eight sites (22 plots) in the longest running forest monitoring network in Alaska, spanning ~350 km of …

Genetic Discovery And Risk Characterization In Type 2 Diabetes Across Diverse Populations, Linda M Polfus, Burcu F Darst, Heather Highland, Xin Sheng, Maggie C Y Ng, Jennifer E Below, Lauren Petty, Stephanie Bien, Xueling Sim, Wei Wang, Pierre Fontanillas, Yesha Patel, Michael Preuss, Claudia Schurmann, Zhaohui Du, Yingchang Lu, Suhn K Rhie, Joseph M Mercader, Teresa Tusie-Luna, Clicerio González-Villalpando, Lorena Orozco, Cassandra N Spracklen, Brian E Cade, Richard A Jensen, Meng Sun, Yoonjung Yoonie Joo, Ping An, Lisa R Yanek, Lawrence F Bielak, Salman Tajuddin, Aude Nicolas, Guanjie Chen, Laura Raffield, Xiuqing Guo, Wei-Min Chen, Girish N Nadkarni, Mariaelisa Graff, Ran Tao, James S Pankow, Martha Daviglus, Qibin Qi, Eric A Boerwinkle, Simin Liu, Lawrence S Phillips, Ulrike Peters, Chris Carlson, Lynne R Wikens, Loic Le Marchand, Kari E North, Steven Buyske, Charles Kooperberg, Ruth J F Loos, Daniel O Stram, Christopher A Haiman

Faculty, Staff and Student Publications

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the

The Giant Axolotl Genome Uncovers The Evolution, Scaling, And Transcriptional Control Of Complex Gene Loci, Siegfried Schloissnig, Akane Kawaguchi, Sergej Nowoshilow, Francisco Falcon, Leo Otsuki, Pietro Tardivo, Nataliya Timoshevskaya, Melissa C. Keinath, Jeramiah J. Smith, S. Randal Voss, Elly M. Tanaka

Biology Faculty Publications

Vertebrates harbor recognizably orthologous gene complements but vary 100-fold in genome size. How chromosomal organization scales with genome expansion is unclear, and how acute changes in gene regulation, as during axolotl limb regeneration, occur in the context of a vast genome has remained a riddle. Here, we describe the chromosome-scale assembly of the giant, 32 Gb axolotl genome. Hi-C contact data revealed the scaling properties of interphase and mitotic chromosome organization. Analysis of the assembly yielded understanding of the evolution of large, syntenic multigene clusters, including the Major Histocompatibility Complex (MHC) and the functional regulatory landscape of the Fibroblast Growth …

Nanopore Guided Regional Assembly, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are the “caps” of the chromosomes and their vital role is to protect them. Possible telomere dysfunction caused by telomere rearrangements can be fatal for the cell and result in age-related diseases, including cancer. The telomeres and subtelomeres are regions that are hard to investigate. The current technology cannot provide their complete sequence, instead the DNA is given in multiple pieces. Current methods of assembling the pieces of these regions are not accurate enough due to the region’s high variability and complex repeated patterns. We propose a hybrid assembly method, the NPGREAT, which utilizes two of the latest …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

A Timeline Of Oculocutaneous Albinism, Mohammed Abushanab, Maria Ceroni, Kimberly Morán

Undergraduate Research Symposium Posters

The purpose of this research timeline is to synthesize the natural history of Oculocutaneous Albinism (OCA), discover gaps in knowledge, as well as understand the genes and mutations that incite the disease. It is through methods of literature-based research that we found the earliest recognition of OCA and investigated it up to its most current state of research. The rate of research remains steady and continuous with the focus varying widely; either by examining more of the genes involved in the disease or by taking more in-depth looks at mutational analyses of genes that are already observed to be linked …

An Investigation On The History And Current Research Of Fragile X Syndrome, Makeda Asare, Isabelle Avenido, Maxene Vergonia-Fehlman

Undergraduate Research Symposium Posters

The purpose of this research is to synthesize the history of Fragile X Syndrome through literature-based research in order to assess the scope of research, population variation, social impact, and treatment. Fragile X was first documented in 1943 by Dr. Julia Bell and Dr. James Purdon Martin in a report of a family case study in which eleven males across two generations showed symptoms of intellectual disabilities. Fragile X Syndrome is an X-linked disorder caused by mutation in the Fragile X mental retardation 1(FMR1) gene on chromosome Xq27.3. The FMR1 mutations are triplet repeat expansion of the CGG repeat sequences …

The History And Future Of Cystic Fibrosis, Randall Combs, Che Fung Andy Chan, Daisy Sahagun

Undergraduate Research Symposium Posters

The purpose of this research timeline is to highlight the tumultuous yet inspiring history of Cystic Fibrosis disease and treatment to give us a more pragmatic understanding of its current state. Cystic Fibrosis is an autosomal recessive disease, most often caused by a single amino-acid deletion of phenylalanine at position 508 in the nucleotide binding domain, which results in a loss of the cystic fibrosis transmembrane conductance regulator (CFTR). Symptomatology varies considerably but a buildup of mucus in the respiratory tract leading to lung failure, and exocrine pancreatic insufficiency which results in digestive and metabolic dysfunction are commonly, if not …

Retinoblastoma: Past, Present, And Future, Izabela Daneva, Crysty-Ann Olaco, Albert Tran

Undergraduate Research Symposium Posters

The purpose of this research timeline is to synthesize the natural history of retinoblastoma to understand its societal effects and develop a public health message to raise awareness of the disease. We used literature-based research in order to gain an understanding about the discovery of this disease and investigate its most current state of knowledge. Retinoblastoma is an intraocular cancer that manifests early in childhood. It is typically linked to a somatic or germline insertion, deletion, or single-base substitution mutation on both alleles of RB1, a tumor-suppressor gene. Retinoblastoma was first identified in 1809 by James Wardrop, and since then, …

Study Of Sickle Cell Disease, Aaron Guevarra, Carlos Herrera, Faysal Ali

Undergraduate Research Symposium Posters

The purpose of this research timeline is to explore the history, prevalence, and effects of Sickle Cell Disease (SCD) so that treatments and possible future experiments or cures may be discussed. In SCD, abnormal red blood cells appear as sickle shaped as opposed to the round shape of normal red blood cells. It is inherited in an autosomal recessive pattern, so an individual must inherit two copies of the allele. The gene mutation is a single nucleotide mutation in the gene which codes for β-globin. In 1910, James B. Herrick first described the disease, and in 1949, its inheritance pattern …