Life Sciences Commons^™

Winner's Curse Correction And Variable Thresholding Improve Performance Of Polygenic Risk Modeling Based On Genome-Wide Association Study Summary-Level Data, Jianxin Shi, Ju-Hyun Park, Jubao Duan, Sonja T. Berndt, Winton Moy, Kai Yu, Lei Song, William Wheeler, Xing Hua, Debra Silverman, Montserrat Garcia-Closas, Chao Agnes Hsiung, Jonine D. Figueroa, Victoria K. Cortessis, Nuria Malats, Margaret R. Karagas

Dartmouth Scholarship

Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner’s-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied …

Siddhartha Mukherjee. The Gene. An Intimate History. New York: Scribner, 2016. 593 Pp. $32.00 Cloth (Isbn 978-1-4767-3350-0), Aldemaro Romero Jr.

Publications and Research

Heredity has always been, in one form or another, at the center of biological

research. There is little doubt that the first scientific experimentation took place

about fifteen thousand years ago, when humans started breeding plants and

animals in order to domesticate them. Today the science of genetics seems to

advance at such a pace that even the experts have trouble keeping up with all the

developments. Now we are witnessing the expansion of our understanding of this

realm of science to levels unimaginable just a few decades ago.

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations & Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Molecular Measurement Of Toxicity In Fish; Case Examples And Policy Implications, Jessica A. Freedman

Senior Honors Projects

Stormwater and oil are common urban contaminants that can be harmful to fish species. One way of recognizing exposed and impaired fish is by monitoring gene expression and gene induction. This study focused on the identification and validation of reference genes for measuring contaminant-induced changes in gene expression due to urban influence. In this study, reference genes (which are genes used to normalize data and remain consistent in varying exposures regardless of organism and tissue type) were established. Six genes were identified as reference genes (ef1a, wdtc1, mtm1, spop, rxrba and tuba1) from a longer list of potential …

A Genetic Analysis Of Cichlid Scale Morphology, Kenta C. Kawasaki

Masters Theses

Epidermal appendages are found on every vertebrate this world has to offer. In fish, these are commonly represented by scales. While we have a solid grasp of how scales develop, little is known about the underlying genetic mechanisms behind these phenotypic changes. Using two species of African cichlids (Labeotropheus fuelleborni and Tropheops “red cheek”) with varying scale phenotypes, we sought to examine their F2 hybrid offspring and statistically link the responsible genetic elements to their respective parental phenotypes through Quantitative Loci Trait (QTL) analysis.

Scales were removed from six different locations across the midline of each individual. Then, numerous …

Inter-Correlations Between Laboratory Inter-Correlations Between Laboratory And Field-Based Tests Of Muscle Contractile Power, Mitchell J. Cameron, Robert Robergs

International Journal of Exercise Science

International Journal of Exercise Science 9(5): 635-645, 2016. Muscle contractile properties have previously been distinguished by fiber typing muscle samples obtained from needle biopsy; however due to conflicting evidence regarding sampling bias and the related need for multiple biopsies, it is not certain if these results are a reliable reflection of whole muscle fiber type expression. Inter-correlations between laboratory and field-based measures of muscle contractile power were used to determine which assessments best discriminate between participants of varying sprint performance, and indirectly reveal potential for power vs. endurance exercise performance. Healthy active male (n=32) and female (n=17) participants were recruited …

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus …

Genetic And Transcriptional Analysis Of Human Host Response To Healthy Gut Microbiota, Michael B. Burns, Allison L. Richards, Adnan Alazizi, Luis B. Barreiro, Roger Pique-Regi, Ran Blekhman, Francesca Luca

Biology: Faculty Publications and Other Works

Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota for human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes whose expression changed at various time points following coculturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with …

Gene Discovery In Mendelian And Complex Diseases, Sali Farhan

Electronic Thesis and Dissertation Repository

Through the Finding of Rare Disease Genes in Canada (FORGE Canada) initiative, individuals affected with rare Mendelian diseases were clinically ascertained with a goal of identifying the genetic origin of their disease. Herein, I describe the methods for identifying the genetic basis of four Mendelian diseases. The application of next generation sequencing led to the discovery of non-synonymous variation in the DNA of individuals affected by rare diseases. The effects of the candidate variants were assessed using a series of functional experiments to complement the human genetics data. The variants observed in patients’ cells are extremely rare, were consistently predicted …

Associations Of Single Nucleotide Polymorphisms In The Bovine Prolactin, Melatonin Receptor 1a, And Dopamine Receptor D2 Genes With Hair Coat Shedding Scores And Productivity Traits In Beef Cattle, Laura R. Meyer

Graduate Theses and Dissertations

Calving rate is a qualitative trait regulated by several genes and is strongly affected by the environment. With the development of biotechnology and gene identification, scientists are able to determine which genes affect these productivity traits to improve accurate selection decisions. Prolactin (PRL) has been associated with reproductive traits, melatonin receptor 1a (MTNR1A) has been associated with meat quality traits, and the dopamine receptor D2 (DRD2) gene has been associated with hair coat score (HCS) in cattle. Our objective was to determine associations between mutations in the PRL, MTNR1A, and DRD2 genes and cow-calf profitability traits. Genomic DNA was extracted …

Investigating Genetic Differences Between Strains Of Janthinobacterium Lividum On Salamanders And In Their Environment, Rhiannon E. Black

Chancellor’s Honors Program Projects

No abstract provided.

Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake

USF Tampa Graduate Theses and Dissertations

Malaria is a devastating global health issue that affects approximately 200 million people yearly and over half a million deaths are caused by this parasitic protozoan disease. Most commercially available drugs only target the blood stage form of the parasite, but the only way to ensure proper elimination is to treat the exoerythrocytic stages of the parasite development cycle. There is a demand for the discovery of new liver stage antimalarial compounds as there are only two current FDA approved drugs for the treatment of liver stage parasites, one of which fails to eliminate dormant forms and the other inducing …

Gene Set Enrichment And Projection: A Computational Tool For Knowledge Discovery In Transcriptomes, Karl Douglas Stamm

Dissertations (1934 -)

Explaining the mechanism behind a genetic disease involves two phases, collecting and analyzing data associated to the disease, then interpreting those data in the context of biological systems. The objective of this dissertation was to develop a method of integrating complementary datasets surrounding any single biological process, with the goal of presenting the response to a signal in terms of a set of downstream biological effects. This dissertation specifically tests the hypothesis that computational projection methods overlaid with domain expertise can direct research towards relevant systems-level signals underlying complex genetic disease. To this end, I developed a software algorithm named …

Reflections On The Current State Of Healthcare Transition For Young Adult Women With Turner Syndrome: Strategies For Facilitating Autonomy And Self-Management, Molly Elizabeth Snyder

Theses and Dissertations

The transition to adult-centered healthcare is a critical period for emerging adults, especially those with special healthcare needs (SHCNs). Considering the ongoing medical monitoring necessary for women with Turner syndrome (TS), it is essential that the transition process be comprehensive and well-coordinated. The aims of this study were to invite young women with TS to reflect on their healthcare transition experiences, to explore participants’ perceived control of their medical management, and to identify ways in which genetic counselors can be involved in multidisciplinary healthcare teams. The hypotheses were that young women with TS are motivated to learn more about their …

Genetic Counseling For Alcohol Use Disorder: Assessment Of Need In Affected And At-Risk Populations, Fayth Michelle Kalb

Theses and Dissertations

Introduction: Alcohol use disorder (AUD) is highly heritable, yet there has been no investigation regarding the possible benefits of genetic counseling for AUD. This study assessed the beliefs individuals with and at risk for AUD have regarding recurrence risk and etiology of AUD, how the presence of the condition in themselves or their family history has affected their lifestyle decisions, and potential benefit from AUD genetic counseling. Methods: An online questionnaire was distributed through social media to support groups for AUD inviting adults 18 years and older with a personal or family history of AUD. Results: Of the 122 individuals …

The Undiagnosed Patient And The Diagnostic Odyssey: Current Genetic Counseling Practices And Perspectives, Amelia Cordell Wardyn

Theses and Dissertations

Patients seen in genetics clinics often endure a diagnostic odyssey in their search for answers for their medical symptoms. This time is not only challenging for patients and their families, but also for the genetic counselors who are trying to help the patients. Previous research has shown that parents of children with undiagnosed medical disorders have specific goals and reasons for wanting to find a diagnosis, and there are many difficulties faced by these parents. Genetic counselors often serve as a prominent figure during the diagnostic odyssey, but little known research has assessed the current practices of and impact that …

Characterization Of The Marine Sponge Amphimedon Compressa Microbiome Across A Spatial Gradient, Renee Michelle Potens

HCNSO Student Theses and Dissertations

Diverse and ecologically important microbial communities (microbiomes) are symbiotic within marine sponges. In this study, the microbiome of Amphimedon compressa from three sample locations (Broward and Dade Counties, Southeast Florida, USA and the Southern Caribbean, Bocas del Toro, Panama) is characterized using 16S rRNA Illumina sequencing. The predominant taxa are Proteobacteria and Cyanobacteria, as expected for Low Microbial Abundance sponges, accounting for over 53% of the total microbiome community. The numbers of Operational Taxonomic Units (OTUs) decrease from Broward County (2,900) to Dade County (2,300) and then Bocas del Toro (1,200). The correlates to a decreasing north-south gradient of …

Regulation Of Ampa-Type Glutamate Receptor Homolog Glr-1 By Erad Ubiquitin Ligases In C. Elegans, Sam Witus

Scholars Week

Endoplasmic reticulum-associated degradation (ERAD) maintains cellular health by removing misfolded proteins from the endoplasmic reticulum (ER). ERAD is ubiquitin-dependent, and ubiquitination of target proteins can be catalyzed by ER-resident E3 ubiquitin ligases. In C. elegans, genes for three putative ERAD E3 ubiquitin ligases have been identified: hrd-1, hrdl-1, and marc-6 (HRD-1, GP78/AMFR, and MARCH-6 in mammalian systems). In C. elegans, these three genes cooperate to maintain the overall health of animals during ER stress. We are testing the roles of hrd-1, hrdl-1, and marc-6 in the neurons of C. elegans. GLR-1 is a glutamate receptor that is expressed in a …

The Effects Of Epigenetics On Stress Response, Kevin Suddarth

Themis: Research Journal of Justice Studies and Forensic Science

Despite the vast amount of resources at the disposal of humanity today, the intricacies of human biology are often a mystery. The chemical and biological products of the human genome have been well studied and documented, but many of the chemical and neurological pathways are missing quite a few details. The human stress response is one of the most primal and valuable functions of this code that developed as a self- preservation mechanism (Hans, 1975) to naturally increase the odds of procreation. However, this function is prone to overload, particularly in individuals with certain epigenetic traits instilled by early life …

Investigation Into The Genetic Basis Of Leaf Shape Morphology In Grapes, Brigette Rachelle Williams

MSU Graduate Theses

Leaves are a highly distinguishing characteristic in grape (Vitis vinifera) and display great diversity in comparison to other crops. However, little is known about the genetic basis of leaf shape in grape. Here, morphometrics and 40,724 single-nucleotide polymorphisms (SNPs) are correlated to describe the relationship between genotype and phenotype of leaf shape in grape. Parent vines (Norton and Cabernet Sauvignon) and their F1 progeny make up the mapping population located at the State Fruit Experiment Station, Genomics Research Vineyard on Missouri State University campus in Mountain Grove, Missouri. Important leaf shape characteristics (n=17) were identified based on the venation pattern, …

Social And Scientific Implications Of Genetic Testing In The Digital Age, Yaruska A. Ordinola

Senior Honors Projects

From Mendel’s law of inheritance in the 19th century through Watson and Crick’s revolutionary observations of the double helix in the 20th century, genetics has been a fascinating and continuing topic of discussion in the field of science (Collins & McKusick, 2001). Major studies like the Human Genome Project (HGP), initiated in 1990 and completed in 2003, provided a starting point from which scientists could more thoroughly investigate the human condition on a genetic level. Arising from this study, personal genomics is considered a blooming field in genetics- in which rapidly developing technological advances are able to provide easier and …

Identifying Genetic Factors In Streptococcus Uberis That Enable Evasion Of The Host Immune Response, Alexis Christine Burnham

Chancellor’s Honors Program Projects

No abstract provided.

Congenic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Saasha Le

Electronic Theses and Dissertations

Breast cancer is a complex disease affected by genetic, epigenetic and environmental factors. The genetic architecture of breast cancer comprises of high to low penetrance alleles. Although low penetrance alleles associate with a small change in an individual’s risk to breast cancer, the total number of variants present and the high population frequency attributes to a much greater population based impact compared to rare high penetrance alleles. Animal models have been used to study these low penetrance modifier alleles in breast cancer. Different rat strains vary in their susceptibility to 7,12- dimethybenzanthracene (DMBA) induced mammary carcinogenesis, with the Wistar- Furth …

Analysis Of Lung Microbiota In Bronchoalveolar Lavage, Protected Brush And Sputum Samples From Subjects With Mild-To-Moderate Cystic Fibrosis Lung Disease, Deborah A. Hogan, Sven D. Willger, Emily L. Dolben, Thomas H. Hampton, Bruce A. Stanton, Hilary G. Morrison, Mitchell L. Sogin, Julianna Czum, Alix Ashare, Michael Tunney

Dartmouth Scholarship

Individuals with cystic fibrosis (CF) often acquire chronic lung infections that lead to irrevers- ible damage. We sought to examine regional variation in the microbial communities in the lungs of individuals with mild-to-moderate CF lung disease, to examine the relationship between the local microbiota and local damage, and to determine the relationships between microbiota in samples taken directly from the lung and the microbiota in spontaneously expectorated sputum. In this initial study, nine stable, adult CF patients with an FEV1>50% underwent regional sampling of different lobes of the right lung by bronchoalveolar lavage (BAL) and protected brush (PB) sampling …

Unique Features Of A Global Human Ectoparasite Identified Through Sequencing Of The Bed Bug Genome, Joshua B. Benoit, Zach N. Adelman, Klaus Reinhardt, Amanda Dolan, Monica Poelchau, Emily C. Jennings, Elise M. Szuter, Richard W. Hagan, Hemant Gujar, Jayendra Nath Shukla, Fang Zhu, M. Mohan, David R. Nelson, Andrew J. Rosendale, Christian Derst, Valentina Resnik, Sebastian Wernig, Pamela Menegazzi, Christian Wegener, Nicolai Peschel, Jacob M. Hendershot, Wolfgang Blenau, Reinhard Predel, Paul R. Johnston, Panagiotis Ioannidis, Robert M. Waterhouse, Ralf Nauen, Corinna Schorn, Mark-Christoph Ott, Frank Maiwald, Subba R. Palli

Entomology Faculty Publications

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome …

The Role Of Rapgap1 In Sxl Activation In Drosophila Melanogaster, Katherine M. Barnes

Lewis Honors College Capstone Collection

The master switch of the sexual differentiation and dosage compensation pathway in Drosophila is the sex lethal gene, Sxl. The early promoter, SxlPe, is activated in females, resulting in female-specific splicing of later transcripts (notably the late Sxl transcript SxlPm), while inactive in males. Chromatin immunoprecipitation (ChIP) assays have previously shown association of two conventionally heterochromatin-localized proteins, HOAP and HP1, at SxlPe, and in situ hybridization as well as RT-PCR assays have confirmed a repressive role for HOAP and both repressive and activating roles for HP1. The mechanism for the activity shift of HP1 is currently unknown. Deletions in the …

Principles Of Biology, Robert Bear, David Rintoul, Bruce Snyder, Martha Smith-Caldas, Christopher Herren, Eva Horne

Open Access Textbooks

This textbook is designed specifically for Kansas State's Biology 198 Class. The course is taught using the studio approach and based on active learning. The studio manual contains all of the learning objectives for each class period and is the record of all student activities. Hence, this textbook is more of a reference tool while the studio manual is the learning tool.

The textbook was originally published and is also available to download at http://cnx.org/contents/db89c8f8-a27c-4685-ad2a-19d11a2a7e2e@24.1.It is licensed under a Creative Commons Attribution License 4.0 license.

Evaluation Of Parameter Estimation And Field Application Of Transgenerational Genetic Mark-Recapture, Ryan W. Whitmore

Cal Poly Humboldt theses and projects

Use of a genetic-based analogue of the traditional mark-recapture method (transgenerational genetic mark-recapture, tGMR) is rapidly expanding as a means to estimate total escapement of Pacific salmon. The tGMR approach is similar to the simple Lincoln-Peterson mark-recapture method. In tGMR, adults returning to fresh water to spawn are collected in the first sampling occasion and their juvenile offspring that are migrating out to sea are collected during the second sampling occasion. Recaptures are determined by the number of parent-offspring pairs identified through genetic parentage analysis of the adult and juvenile collections. Two versions of tGMR are currently in use, referred …

Genetic Basis Of Variation For Within-Boll Yield Components In Cotton, Imtiaz Ali, Amir Shakeel, Asif Ali, Bushra Sadia

Turkish Journal of Agriculture and Forestry

Cotton productivity on a per-hectare basis is low in Pakistan. As boll is the basis for seed cotton yield, within-boll yield components can potentially serve as the most basic determinants of cotton productivity on a per unit land area basis. Before attempting the improvement of any trait, it is necessary to know the genetic mechanism lying behind its inheritance. The current study aimed to estimate the genetic basis of within-boll yield components in cotton. The research trials were conducted at the research area of the Department of Plant Breeding and Genetics, University of Agriculture, Faisalabad, Pakistan. Epistasis was found to …