Genetics and Genomics Commons^™

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations and Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

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 …

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

Honors Program: Senior Projects (Public)

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 …

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 …

Gene-Based Association Study For Lipid Traits In Diverse Cohorts Implicates Bace1 And Sidt2 Regulation In Triglyceride Levels, Angela Andaleon, Lauren S. Mogil, Heather Wheeler

Bioinformatics Faculty Publications

Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol (P = 9.0 × 10⁻¹⁰) and …

Qatar: Diabetes, Diangelo Gonzalez

Global Public Health

The State of Qatar is a developed nation that is located in the Middle East and borders the Persian Gulf and Saudi Arabia. The nation is a constitutional monarchy and is currently led by Amir Tamim bin Hamad Al Thani. The 2,300,000+ people of Qatar face many major challenges. Although it is one of the wealthiest nations in the Middle East, Qatar faces issues of human trafficking, migrants willing to work in poor conditions, and Middle Eastern Respiratory Syndrome (MERS). The most critical issue that plagues this county is diabetes, both I and II. Diabetes is a disease that is …

Movement In Cats, Valerie N. Plummer

College of Graduate Studies: Theses & Dissertations

Feral cats (Felis catus) are listed as one of the '100 world's worst invasive alien species'. There are as many as 70-100 million feral cats in the United States as well as an estimated 117-157 million domestic indoor and outdoor cats. Management efforts include a nonlethal feeding and sterilization program known as "trap-neuter-release" (TNR) where cats are surgically sterilized and returned to the environment. Population size and structure, immigration rates, spay/neuter rates, and data on spatial use all play a role in whether TNR is a viable management option. This study focuses on population structure and spatial use. …

Three Methodological Innovations In Race And Ethnicity Research, Jeffrey Napierala

Legacy Theses & Dissertations (2009 - 2024)

This dissertation examines topics related to racial and ethnic diversity through three essays. Each essay takes a new perspective on a current issue in the literature and utilizes a unique statistical methodology to address that issue. The first essay uses the Monte Carlo Simulation Method to develop a measure of segregation for the ACS and uses it to assess whether the ACS is useful for measuring segregation in places with different sizes. The second essay considers whether a relatively unexplored factor, genetics, is correlated with migration. This perspective broadens our understanding of why migration occurs and is perpetuated over time. …

Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer

Biological Sciences Faculty Publications

Viral gain-of-function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …

Crispr Genetic Editing: Paths For Christian Acceptance And Analysis Of In Vivo And In Vitro Efficiency, Mandeep Sandhu

Scripps Senior Theses

With advancements in CRISPR-cas9 broadening the potential paths for clinical usage of genetic editing, conversations about genetic editing have grown to outside simply scientific communities and into mainstream conversations. This study focuses specifically on Christian discourse of genetic editing and locates four major tensions for many Christians when they think about genetic editing: beginning of life, Creator-human relationship, imago Dei, and stewardship. With these major concerns in mind, I identify epigenetics, somatic cell genetic editing, and in vivo genetic editing research as important research paths to pursue as they can potentially produce techniques that more Christian individuals would feel comfortable …

Natural And Anthropogenic Drivers Of Tree Evolutionary Dynamics, Brandon M. Lind

Theses and Dissertations

Species of trees inhabit diverse and heterogeneous environments, and often play important ecological roles in such communities. As a result of their vast ecological breadth, trees have become adapted to various environmental pressures. In this dissertation I examine various environmental factors that drive evolutionary dynamics in threePinusspecies in California and Nevada, USA. In chapter two, I assess the role of management influence of thinning, fire, and their interaction on fine-scale gene flow within fire-suppressed populations of Pinus lambertiana, a historically dominant and ecologically important member of mixed-conifer forests of the Sierra Nevada, California. Here, I find evidence …

Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang

Capstones

As science has progressed, scientists have realized that evidence goes beyond the realms of physical sight. Whether it is too small or difficult to find, scientists have developed different ways to get around this problem. We see this in cancer genomics and in extrasolar planetary research. Scientists use what they know and what they measure to validate their work.

https://lucy-huang-9tge.squarespace.com/

Glutamylation Regulates Transport, Specializes Function, And Sculpts The Structure Of Cilia, Robert O'Hagan, Malan Silva, Ken Cq Nguyen, Winnie Zhang, Sebastian Bellotti, Yasmin Ramadan, David Hall, Maureen M. Barr

Department of Biology Faculty Scholarship and Creative Works

Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a “Tubulin Code” that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of kinesin-2 OSM-3/KIF17, while a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here, we examine the role of PTMs and the Tubulin Code in the cililary …

Pleiotropy Of Genetic Variants On Obesity And Smoking Phenotypes: Results From The Oncoarray Project Of The International Lung Cancer Consortium, Tao Wang, Jee-Young Moon, Yiqun Wu, Christopher I. Amos, Rayjean J. Hung, Adonina Tardon, Angeline Andrew, Chu Chen, David C. Christiani, Demetrios Albanes, Erik H. F. M. Van Der Heijden, Eric Duell, Gadi Rennert, Gary Goodman, Geoffrey Liu, James D. Mckay, Jian-Min Yuan, John K. Field, Jonas Manjer, Kjell Grankvist, Lambertus A. Kiemeney, Loic Le Marchand, M. Dawn Teare, Matthew B. Schabath, Mattias Johansson, Melinda C. Aldrich, Michael Davies, Mikael Johansson, Ming-Sound Tsao, Neil Caporaso, Susanne Arnold

Internal Medicine Faculty Publications

Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p < 0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p < 0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) …

Reevaluating The Occurrence And Phylogeny Of The Pigtoe Unionid Mussels Fusconaia Askewi, Fusconaia Lananensis, Fusconaia Flava, And Pleurobema Riddelli In Texas, Charles J. Pratt

Biology Theses

The recent development of DNA-based species classification methods has led to the revision of many morphology-based species designations as genetic data has provided new information for species delineation. Analysis of standardized DNA ‘barcoding’ gene regions has proven particularly effective in resolving the taxonomic status of taxa that display phenotypic and habitat overlap.

Freshwater Unionid and Margaritiferid mussels comprise one of the most diverse aquatic taxa in North America, but are also among the most threatened, with over 70% of the approximately 300 native species considered at-risk or in decline. Although mussels face extensive threats from anthropogenic activity, conservation efforts have …

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same …

Genome Wide Association And Next Generation Sequencing Approaches To Map Determinants Of Ascites In Broiler Chickens, Shatovisha Dey

Graduate Theses and Dissertations

These studies have investigated different candidate genomic regions for their contributions to ascites in broilers. Ascites syndrome is a manifestation of idiopathic pulmonary arteriole hypertension that concerns the poultry industry worldwide. Investigations have demonstrated the disease to be genetically regulated and to exhibit moderate to high heritabilities. Although previous studies have indicated a few chromosomes to be involved with ascites, no genes have been identified to date with direct links to the disease. This dissertation presents a collection of studies that determine the genomic and genetic interactions for regions on chromosome 2 and 9 for ascites phenotypes in broiler chickens. …

Comprehensive Assessments Of The Genetic Determinants In Salmonella Typhimurium For Fitness Under Host Stressors: Oxidative Stress And Iron Restriction, Sardar Abdullah

Graduate Theses and Dissertations

Salmonella is an intracellular pathogen that infects a wide range of hosts. The infected host utilizes reactive oxygen species (ROS) and iron-restriction to eliminate the pathogen. We used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2O2. For Tn-seq, a highly saturated Tn5 library was grown in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets of overlapping genes that are required for resistance of S. Typhimurium to H2O2L and H2O2H, and the results were validated via phenotypic evaluation of 50 selected mutants. The enriched …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus

Physiology Faculty Publications

Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …

Analysis Of Population Structure In A California Newt (Taricha Torosa) Metapopulation, Jessica Vincent

Mahurin Honors College Capstone Experience/Thesis Projects

As anthropogenic influences take an ever-increasing toll on the environment, understanding how environmental change affects species is paramount. Concern regarding decline in amphibian populations has spurred research examining the effects of habitat change on the dynamics of populations at landscape levels. One important goal is to understand how gene flow among populations is affected by changes in habitat. Biologists need to consider the relationship between gene flow and habitat alterations so that movements among individual breeding ponds can be maintained over time, reducing risk of local extinction events. This study focuses on patterns of gene flow among thirteen populations of …

Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew Mcdermut

Undergraduate Research Symposium Posters

A highly novel Streptomyces phage, Satis, was isolated from a direct environmental sample collected from outside Danforth House on the Washington University campus. Satis infects bacterial species Streptomyces lividans producing pinpoint, cloudy plaques less than 1mm in diameter. Electron microscope data shows rare atypical physical features. Rather than the common octahedral capsid shape, Satis has a prolate head with visible cross-linked hexagonal protein structure and average measurements of 285 nm by 47 nm with a long, flexible tail measuring 268 nm. Upon sequencing, it was found that Satis contains the longest phage genome discovered to date through the SEA-PHAGE program …

Software Development For Genome Sequence Analysis, David Farr

Symposium Of University Research and Creative Expression (SOURCE)

The cost of genome sequencing has decreased rapidly, expanding availability for many biological applications (Muir 2016). For example, researchers can now obtain genome sequences from multiple populations under different types of selection. Comparison of these sequences allows for identification of chromosome regions and specific genes associated with adaptive evolution (Kelly 2013). As an increasing number of researchers engage in this type of inquiry, many have created in-house computer scripts to analyze the raw sequence data (e.g., Kelly 2013), creating a gap in both continuity and standardization.

Using a test dataset and preliminary results from an ongoing artificial selection experiment in …

Does Genotype Correlate With Phenotype? Evaluating Ruffed Lemur (Varecia Spp.) Color Vision Using Subject Mediated Automatic Remote Testing Apparatus (Smarta), Raymond Vagell

Theses and Dissertations

Ruffed lemur (Varecia spp.) color vision research was conducted using a multidisciplinary approach: psychophysics, genetic analysis, technology, and animal training. The behavioral manifestation of Varecia spp. trichromacy was shown using a touchscreen apparatus (SMARTA). Trichromats performed better than dichromats when discriminating red from green (G₂ = 78.10, p < 0.001).

Investigating The Genetic Basis For Hominoid Taillessness, Samantha M. Tickey-Mccrane, Holly Dunsworth, Johanna E. Wegener

Senior Honors Projects

Investigating the Genetic Basis for Hominoid Taillessness:

A Comparative Genetic Approach Across Ten Catarrhine Taxa

Samantha Tickey-McCrane1,2, Johanna E. Wegener2, and Holly Dunsworth1

Honors Thesis Abstract Written by Samantha Tickey-McCrane, Departments of Anthropology & Biology

Advisor: Dr. Holly Dunsworth, Department of Anthropology

How did hominoid tail loss occur? My goals are to test phylogenetic and adaptive hypotheses for tail length variation among macaques, and use those insights to reconstruct the evolution of hominoid taillessness. Further, I aim to ultimately uncover which candidate genes or pathways may be responsible for catarrhine tail loss, and what other traits may be affected by …

Cost Benefit Analysis Of Genetic Markers In Cattle, Josh Crystal

Agricultural Economics and Agribusiness Undergraduate Honors Theses

Genetic sequencing in beef cattle (L. Bos Taurus) is expected to aid producers select cattle with traits that enhance profitability. Using data from experimental trials conducted with Angus, Brahman, and their reciprocal cross, this project analyzes the profitability of grazing endophyte infected tall Fescue (L. Festuca arundinacea Schreb.) vs. Bermuda grass (L. Cynodon dactylon) pasture. The study is unique in the sense that actual cow-calf breeding failure rates (open cows were not culled) were tracked from 1991 to 1997 on herds that were bred to calf in spring and either exposed to fungal endophyte (L.Acremonium coenophialum Morgan-Jones …

The Utilization Of Prenatal Microarray: A Survey Of Current Genetic Counseling Practices And Barriers, Leslie N. Durham, Leslie Durham

Dissertations and Theses (Open Access)

Chromosomal microarray (CMA) assesses chromosome copy number variants (CNVs) missed by standard karyotyping. The American College of Obstetricians and Gynecologists (ACOG) recommends CMA for all patients with fetuses with an ultrasound anomaly and suggests that it be made available to all women undergoing invasive testing. In order to assess prenatal genetic counselors’ (GCs) practices regarding the utilization of CMA we conducted a survey of their current practices, attitudes, and perceived barriers. Of the 192 respondents, 183 (95%) have incorporated CMA into clinical practice with the majority (64%) believing that the benefits of CMA outweigh the harms. However, only half (52%) …

Attitudes Of Clinicians To Wards Cardiac Surgery And Trisomy 18, Meagan Kaulfus

Dissertations and Theses (Open Access)

Trisomy 18 is an autosomal trisomy characterized by minor to major birth defects, severe disabilities, and high rates of pre- and neonatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding surgical treatment of congenital heart defects, which occur in approximately 90% of infants with trisomy 18, is of our study’s interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. In this study, the attitudes of clinicians of multiple specialties towards cardiac surgery for infants with …

Genetic Polymorphisms Of The Glucocorticoid Receptor And Interleukin-8 Receptor Genes Are Related To Production Traits And Hair Coat Score In Crossbred Cattle, Avery Deaton

Animal Science Undergraduate Honors Theses

The objective of this thesis was to identify polymorphisms in the glucocorticoid receptor (GR) and interleukin-8 receptor (CXCR2) genes and to associate genotypes between the above mentioned polymorphisms and production traits in crossbred cattle. The hypothesis was that polymorphisms will exist for GR and CXCR2 genes and will be linked to production traits. Glucocorticoid receptors have been positively associated with higher milk yields, lactose content, feed intake, and feed conversion rates. Interleukin-8 genes are part of the innate immune response and help with many aspects of female reproduction health, such as protecting the embryo from the maternal immune system during …