Digital Commons Network^™

Dopamine Perturbation Of Gene Co-Expression Networks Reveals Differential Response In Schizophrenia For Translational Machinery, Mark Z. Kos, Jubao Duan, Alan R. Sanders, Lucy Blondell, Eugene I. Drigalenko, Melanie A. Carless, Pablo V. Gejman, Harald H. H. Goring

School of Medicine Publications and Presentations

The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology. Transcriptomic profiles were measured by RNA-seq in B-cell transformed lymphoblastoid cell lines from 514 SZ cases and 690 controls, both before and after exposure to DA ex vivo (100 μM). …

Types Of Tobacco Consumption And The Oral Microbiome In The United Arab Emirates Healthy Future (Uaehfs) Pilot Study, Yvonne Vallès, Claire K. Inman, Brandilyn A. Peters, Raghib Ali, Laila Abdel Wareth, Abdishakur Abdulle, Habiba Alsafar, Fatme Al Anouti, Ayesha Al Dhaheri, Divya Galani, Muna Haji, Aisha Al Hamiz, Ayesha Al Hosani, Mohammed Al Houqani, Abdulla Al Junaibi, Marina Kazim, Tomas Kirchhoff, Wael Al Mahmeed, Fatma Al Maskari, Abdullah Alnaeemi, Naima Oumeziane, Ravichandran Ramasamy, Ann Marie Schmidt, Michael Weitzman, Eiman Al Zaabi, Scott Sherman, Richard B. Hayes, Jiyoung Ahn

All Works

© 2018, The Author(s). Cigarette smoking alters the oral microbiome; however, the effect of alternative tobacco products remains unclear. Middle Eastern tobacco products like dokha and shisha, are becoming globally widespread. We tested for the first time in a Middle Eastern population the hypothesis that different tobacco products impact the oral microbiome. The oral microbiome of 330 subjects from the United Arab Emirates Healthy Future Study was assessed by amplifying the bacterial 16S rRNA gene from mouthwash samples. Tobacco consumption was assessed using a structured questionnaire and further validated by urine cotinine levels. Oral microbiome overall structure and specific taxon …

Genetics Of The Thrombomodulin-Endothelial Cell Protein C Receptor System And The Risk Of Early-Onset Ischemic Stroke, John W. Cole, Huichun Xu, Kathleen Ryan,, Thomas Jaworek, Nicole Dueke, Patrick Mcardle, Brady Gaynor,, Yu-Ching Cheng, Jeffrey O'Connell, Ayeesha Kamran Kamal

Section of Neurology

Background and Purpose: Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.

Methods: Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms …

Persistent Misconceptions About Mutations Among Graduate Nursing Students, Jane Garvin, Beverly Collins

Nursing Collection

Purpose

The purpose of this study was to determine the ongoing misconceptions about mutations, an area of rising public interest, among graduate nursing students.

Design

Using a prospective cohort design, graduate students entering a public university in the Fall of 2014 were followed to graduation in the Fall of 2016.

Methods

Knowledge of mutations was assessed with an anonymous pre-test and post-test using three items from the Genomic Nursing Concept Inventory - 2011 beta version developed by Ward. Differences in pre-test and post-test scores were assessed by T-test. Post-test items with > 30% marked incorrectly were examined further; the most frequent …

Re-Thinking Alzheimer's Disease Therapeutic Targets Using Gene-Based Tests, Man Ki Kwok, Shi Lin Lin, C Mary Schooling

Publications and Research

Background: Alzheimer's disease (AD) is a devastating condition with no known effective drug treatments. Existing drugs only alleviate symptoms. Given repeated expensive drug failures, we assessed systematically whether approved and investigational AD drugs are targeting products of genes strongly associated with AD and whether these genes are targeted by existing drugs for other indications which could be re-purposed.

Methods: We identified genes strongly associated with late-onset AD fromthe loci of genetic variants associated with AD at genome-wide-significance and from a gene-based test applied to the most extensively genotyped late-onset AD case (n=17,008)-control (n=37,154) study, the International Genomics of Alzheimer's Project. …

Uncovering The Complex Genetics Of Human Temperament, Igor Zwir, Javier Arnedo, Coral Del-Val, Laura Pulkki-Råback, Bettina Konte, Sarah S. Yang, Rocio Romero-Zaliz, Mirka Hintsanen, Kevin M. Cloninger, Gabriel A. De Erausquin

School of Medicine Publications and Presentations

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic–phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified …

Epidemiology Of Moderate Alcohol Consumption And Breast Cancer: Association Or Causation?, Samir Zakhari, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate …

Diversity And Phylogeny Of Sargassum (Fucales, Phaeophyceae) In Singapore, Zhi Ting Yip, Randolph Z. B. Quek, Jeffrey K. Y. Low, Bryan Wilson, Andrew G. Bauman, Loke Ming Chou, Peter A. Todd, Danwei Huang

Marine & Environmental Sciences Faculty Articles

Sargassum species play key ecological roles on coral reefs, yet their diversity remains poorly known. Precise identification of Sargassum species, however, is improving with molecular genetic tools, though these have yet to be applied rigorously in Singapore. Historical records list 41 species, but no more than ten were verified based on herbarium vouchers, and even fewer (five species) were confirmed in the field based on a single nuclear gene marker in a previous study. Here, we revised the diversity of Sargassum in Singapore by examining all the morphologically distinct forms collected from the local coral reef environment. A total of …

Dobi Studies, Teaches The Marvels Of Genetics, Aldemaro Romero Jr.

Publications and Research

“When I was in third grade, a parent of one of the other students brought a number of cats to the library on a Saturday and talked about how there are all these different hereditary patterns that contribute to their coat colors and appearance, like spots, stripes, and white paws. I was just hooked because I loved cats, and I said this is what I want to do.”

That’s how Dr. Krista Dobi explains why she became a geneticist. A native of North Brunswick, New Jersey, Dobi received a bachelor of arts from Princeton University and a doctorate in genetics …

Random Genetic Drift And Selective Pressures Shaping The Blattabacterium Genome, Austin Alleman, Kate L. Hertweck, Srini Kambhampati

Biology Faculty Publications and Presentations

Estimates suggest that at least half of all extant insect genera harbor obligate bacterial mutualists. Whereas an endosymbiotic relationship imparts many benefits upon host and symbiont alike, the intracellular lifestyle has profound effects on the bacterial genome. The obligate endosymbiont genome is a product of opposing forces: genes important to host survival are maintained through physiological constraint, contrasted by the fixation of deleterious mutations and genome erosion through random genetic drift. The obligate cockroach endosymbiont, Blattabacterium – providing nutritional augmentation to its host in the form of amino acid synthesis – displays radical genome alterations when compared to its most …

Liability Rules For Health Information, Jorge L. Contreras, Francisca Nordfalk

Utah Law Faculty Scholarship

The recent trend toward propertization of health data could pose significant challenges to biomedical research and public health. Property rule systems can result in sizable up-front costs in the acquisition of consent from individual data subjects, as well as the ongoing risk that data subjects will retract consent or object to unanticipated data uses, thus compromising existing data resources and analyses. We argue that property-based approaches to health data should be rejected in favor of liability rule frameworks for the protection of individual privacy interests. We demonstrate that liability rule frameworks for data governance are not only desirable from a …

Confirming World-Wide Distribution Of An Agriculturally Important Lacewing, Chrysoperla Zastrowi Sillemi, Using Songs, Morphology, Mitochondrial Gene Sequencing, And Phylogenetic Reconstruction, Zoe Mandese

Honors Scholar Theses

The Chrysoperla carnea-group of green lacewings is a cryptic species complex. Species within the group are morphologically similar, yet isolated from one another via reproductive mating song. Chrysoperla zastrowi, a species within the carnea-group, is currently described with a distribution ranging from South Africa to the Middle East and India. However, recent collections of carnea-group lacewings from Guatemala and California were preliminarily identified as Chrysoperla zastrowi based upon similarities in their vibrational courtship songs. This analysis aims to place six specimens, collected by collaborators in Guatemala, Armenia, Iran, and California, into a pre-existing phylogeny of the …

Genetics Of A De Novo Origin Of Undifferentiated Multicellularity, Matthew D. Herron, William C. Ratcliff, Jacob Boswell, Frank Rosenzweig

Biological Sciences Faculty Publications

The evolution of multicellularity was a major transition in evolution and set the stage for unprecedented increases in complexity, especially in land plants and animals. Here, we explore the genetics underlying a de novo origin of multicellularity in a microbial evolution experiment carried out on the green alga Chlamydomonas reinhardtii. We show that large-scale changes in gene expression underlie the transition to a multicellular life cycle. Among these, changes to genes involved in cell cycle and reproductive processes were overrepresented, as were changes to C. reinhardtii-specific and volvocine-specific genes. These results suggest that the genetic basis for the experimental evolution …

Genomic Variation Of Introduced Salvinia Minima In Southeastern United States, Carol A. Rowe, Donald P. Hauber, Paul G. Wolf

Ecology Center Publications

Common salvinia, Salvinia minima Baker (Salviniaceae), is a small, floating aquatic fern native to Central and South America that has invaded fresh water bodies in southeastern United States since the 1930s. We examined genetic variation across much of the introduced range of this species in the United States using codominant RAD-seq markers. Data from over 600 variable loci showed a reduction in heterozygosity from east to west in addition to a corresponding trend in assignment of samples to one of two genetic groups. Our data are consistent with previous published work and with the hypothesis that common salvinia had a …

Utilizing Random Regression Models For Genomic Prediction Of A Longitudinal Trait Derived From High‐Throughput Phenotyping, Malachy T. Campbell, Harkamal Walia, Gota Morota

Department of Agronomy and Horticulture: Faculty Publications

The accessibility of high‐throughput phenotyping platforms in both the greenhouse and field, as well as the relatively low cost of unmanned aerial vehicles, has provided researchers with an effective means to characterize large populations throughout the growing season. These longitudinal phenotypes can provide important insight into plant development and responses to the environment. Despite the growing use of these new phenotyping approaches in plant breeding, the use of genomic prediction models for longitudinal phenotypes is limited in major crop species. The objective of this study was to demonstrate the utility of random regression (RR) models using Legendre polynomials for genomic …

Egfr Polymorphisms In Drosophila Melanogaster, Stacie Chue, Neha Mehta, Samantha Poon, Heather Trazino

Publications and Research

No abstract provided.

Sequencing And Analysis Of Centromere Protein B In Wallaby And The Rapid Evolution Of The Centromere, Alexander Tedeschi

Honors Scholar Theses

Using a combination of Sanger sequencing and RNA-seq data, this project aims to determine the nucleotide and amino acid sequence of Centromere Protein B (CENP-B), an important protein involved in the assembly of the kinetochore protein complex at the centromere, in several species of marsupials, specifically wallabies. Despite their recent evolutionary history, these species have been shown to have surprisingly divergent centromeric DNA sequences. Through comparative analysis of these sequences, this project, along with analysis of several other CENPs, aims to determine if this divergence extends to the proteins closely associated with these sequences and possibly even further into the …

Crispr Gene Editing In The Sea Squirt, Ciona Intestinalis, Evelyn Siler, Steven Irvine

Senior Honors Projects

Genetic manipulation has come a long way in the past ten years alone. Scientists have had access to gene editing techniques for decades, but until recently these methods have proven to be expensive and unpredictable. However, thanks to the development of a new, more efficient genome editing strategy called CRISPR/Cas9, more aggressive progress can now be made in genetics research.

CRISPR is not a machine or a physical tool, but rather it is a system that involves introducing a protein into a cell, along with a DNA segment that will attract the protein to a desired location on the DNA. …

Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro

Senior Honors Projects

In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …

Identifying New Genes Involved In Centromere Establishment, Megan Boyer

Honors Scholar Theses

The centromere is a site on the chromosome that mediates accurate cell division by serving as a platform for kinetochore assembly, and microtubule attachment during cell division. Errors in the process of chromosome segregation can contribute to genetic irregularities, such as those seen in cancer and congenital defects. Our lab uses the ectopic centromere as a tool to discover what proteins may be involved in centromere establishment, defined as the deposition of CENP-A at the locus. We use the lacO/LacI system within Drosophila S2 cells that contain a CAL1-GFP- LacI transgene and an integrated lacO array to study the ectopic …

The Undergraduate Training In Genomics (Utrig) Initiative: Early & Active Training For Physicians In The Genomic Medicine Era, Rebecca L. Wilcox, Patricia V. Adem, Ebrahim Afshinnekoo, James B. Atkinson, Leah W. Burke, Hoiwan Cheung, Shoumita Dasgupta, Julia Delagarza, Loren Joseph, Robin Legallo, Madelyn Lew, Christina M. Lockwood, Richard L. Haspel

NYMC Faculty Publications

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student …

Epigenome-Wide Association Study Of Metabolic Syndrome In African-American Adults, Tomi Akinyemiju, Anh N. Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K. Tiwari, Devin Absher, Xin Geng, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies.

Methods: Data on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead …

Obesity And Obesogenic Growth Are Both Highly Heritable And Modified By Diet In A Nonhuman Primate Model, The African Green Monkey (Chlorocebus Aethiops Sabaeus), C. A. Schmitt, S. K. Service, A. J. Jasinska, Thomas D. Dyer, M. J. Jorgensen, R. M. Cantor, G. M. Weinstock, John Blangero, J. R. Kaplan, N. B. Freimer

School of Medicine Publications and Presentations

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity.

STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a …

Genetic Diversity And Distinctness Of Wild Nebraska Hops And Hop Cultivars (Humulus Lupulus L.), Megan Franklin

Honors Theses

Background Commercial hop (Humulus lupulus) cultivars that are being grown in the Midwest are not performing as successfully as when they are grown in the Pacific Northwest, the region to which they are adapted. To increase adaptation to the Midwest environment, one strategy is to draw from the genetic pool of wild native Midwest hops, which have developed genes that allow them to grow successfully in this environment. Wild hop plants that are genetically distinct from commercial cultivars are likely to have more adaptations, such as pest/disease resistance and drought tolerance, which can be bred into commercial lines. The …

Impact Of Model Violations On The Inference Of Species Boundaries Under The Multispecies Coalescent, Anthony J. Barley, Jeremy M. Brown, Robert C. Thomson

Faculty Publications

© 2017 The Author(s). The use of genetic data for identifying species-level lineages across the tree of life has received increasing attention in the field of systematics over the past decade. The multispecies coalescent model provides a framework for understanding the process of lineage divergence and has become widely adopted for delimiting species. However, because these studies lack an explicit assessment of model fit, in many cases, the accuracy of the inferred species boundaries are unknown. This is concerning given the large amount of empirical data and theory that highlight the complexity of the speciation process. Here, we seek to …

Hla-Dqa1 And Apol1 As Risk Loci For Childhood-Onset Steroid-Sensitive And Steroid-Resistant Nephrotic Syndrome., Adebowale Adeyemo, Christopher Esezobor, Adaobi Solarin, Asiri Abeyagunawardena, Jameela A. Kari, Sherif El Desoky, Larry A. Greenbaum, Margret Kamel, Mahmoud Kallash, Cynthia Silva, Alex Young, Tracey E. Hunley, Nilka De Jesus-Gonzalez, Tarak Srivastava, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association.

Study design: Case-control study.

Setting & participants: African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium.

Factor: Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles.

Outcomes: SSNS …

An Exome-Wide Sequencing Study Of Lipid Response To High-Fat Meal And Fenofibrate In Caucasians From The Goldn Cohort, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial …

Advancing Behavioural Genomics By Considering Timescale, Clare C. Rittschof, Kimberly A. Hughes

Entomology Faculty Publications

Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early …

Association Of Interleukin-6 Polymorphisms With Obesity Or Metabolic Traits In Young Mexican-Americans, K. Boeta-Lopez, J. Duran, D. Elizondo, E. Gonzales, Anne R. Rentfro, Andrea E. Schwarzbach, Saraswathy Nair

Health & Biomedical Sciences Faculty Publications and Presentations

Objective The objective of the study is to investigate the association of interleukin-6 (IL6) promoter single-nucleotide polymorphisms rs1800797 (-597 G/A) and rs1800796 (-572 G/C) with obesity or metabolic syndrome in Mexican-Americans.

Methods The rs1800797 and rs1800796 single-nucleotide polymorphisms were genotyped in Mexican-Americans (n = 437) from South Texas, and results were correlated with measures of obesity and metabolic syndrome including body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, liver enzymes, plasma IL6 and high-sensitive C-reactive protein (hs-CRP).

Results Significant associations were found for the rs1800796 variant with increased waist circumference, insulin resistance, lower IL6 levels and higher hs-CRP …

International Consensus Statement On Allergy And Rhinology: Allergic Rhinitis, Sarah K. Wise, Sandra Y. Lin, Elina Toskala, Richard R. Orlandi, Cezmi A. Akdis, Jeremiah A. Alt, Antoine Azar, Fuad M. Baroody, Claus Bachert, Helene J. Krouse

School of Medicine Publications and Presentations

Background:

Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).

Methods:

Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following …