Genetics and Genomics Commons^™

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO₂) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO₂ exposure (i.e., the effects of nTiO₂-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO₂ (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …

Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk, Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Susanne M. Arnold

Markey Cancer Center Faculty Publications

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated …

Horse Y Chromosome Assembly Displays Unique Evolutionary Features And Putative Stallion Fertility Genes, Jan E. Janečka, Brian W. Davis, Sharmila Ghosh, Nandina Paria, Pranab J. Das, Ludovic Orlando, Mikkel Schubert, Martin K. Nielsen, Tom A. E. Stout, Wesley Brashear, Gang Li, Charles D. Johnson, Richard P. Metz, Al Muatasim Al Zadjali, Charles C. Love, Dickson D. Varner, Daniel W. Bellott, William J. Murphy, Bhanu P. Chowdhary, Terje Raudsepp

Veterinary Science Faculty Publications

Dynamic evolutionary processes and complex structure make the Y chromosome among the most diverse and least understood regions in mammalian genomes. Here, we present an annotated assembly of the male specific region of the horse Y chromosome (eMSY), representing the first comprehensive Y assembly in odd-toed ungulates. The eMSY comprises single-copy, equine specific multi-copy, PAR transposed, and novel ampliconic sequence classes. The eMSY gene density approaches that of autosomes with the highest number of retained X–Y gametologs recorded in eutherians, in addition to novel Y-born and transposed genes. Horse, donkey and mule testis RNAseq reveals several candidate genes for stallion …

The Zinc Transporter Zipt-7.1 Regulates Sperm Activation In Nematodes, Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating …

Analysis Of The Immunological Biomarker Profile During Acute Zika Virus Infection Reveals The Overexpression Of Cxcl10, A Chemokine Linked To Neuronal Damage., Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco Da Silva, Valdinete Alves Do Nascimento, Dana Cristina Da Silva Monteiro, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis.

OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection.

METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining.

FINDINGS: ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite …

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10^‐6). Rare variant and gene expression changes …

Genome-Wide Interactions With Dairy Intake For Body Mass Index In Adults Of European Descent, Caren E. Smith, Jack L. Follis, Hassan S. Dashti, Toshiko Tanaka, Mariaelisa Graff, Amanda M. Fretts, Tuomas O. Kilpeläinen, Mary K. Wojczynski, Kris Richardson, Mike A. Nalls, Christina-Alexandra Schulz, Yongmei Liu, Alexis C. Frazier-Wood, Esther Van Eekelen, Carol Wang, Paul S. De Vries, Vera Mikkilä, Rebecca Rohde, Bruce M. Psaty, Torben Hansen, Mary F. Feitosa, Chao-Qiang Lai, Denise K. Houston, Luigi Ferruci, Ulrika Ericson, Zhe Wang, Renée De Mutsert, Wendy H. Oddy, Ester A. L. De Jonge, Ilkka Seppälä, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption.

Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction <10⁻⁷⁾, and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, …

Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu

Molecular and Cellular Biochemistry Faculty Publications

Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, …

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …