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Investigating Phenotypic Severity Associated With Sister Chromatid Cohesion Defects In Human Disease, Stefanie Marie Percival Jan 2017

Investigating Phenotypic Severity Associated With Sister Chromatid Cohesion Defects In Human Disease, Stefanie Marie Percival

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INVESTIGATING PHENOTYPIC SEVERITY ASSOCIATED WITH SISTER CHROMATID COHESION DEFECTS IN HUMAN DISEASE STEFANIE M. PERCIVAL GRADUATE BIOMEDICAL SCIENCES ABSTRACT Sister chromatid cohesion (SCC) is a process that utilizes a proteinaceous ring, cohesin, for accurate chromosome segregation. An essential process in S phase termed cohesion establishment is necessary to stabilize cohesin rings around sister chromatids. Mutations in establishment of cohesion homolog 2 (ESCO2), a protein essential for cohesion establishment, cause a developmental disorder called Roberts Syndrome (RBS). Cytogenetic analysis in patients reveals heterochromatic repulsion (HR), a centromeric puffing, indicative of cohesion defects. The severity of phenotypes varies from preterm lethal to …

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Thermodynamics And Kinetics Of Gel-Sol And Liquid-Liquid Phase Transitions: Effects Of Solid Surfaces And Nanoconfinement, Jennifer Rachel Prado Jan 2017

Thermodynamics And Kinetics Of Gel-Sol And Liquid-Liquid Phase Transitions: Effects Of Solid Surfaces And Nanoconfinement, Jennifer Rachel Prado

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This research explores the effects of nanoconfinement and solid surfaces on gel-sol and liquid-liquid phase transitions through the changes in the thermodynamics and kinetics. The transitions that occur in the presence of solid surfaces were studied calorimetrically and compared to bulk. Two systems, gelatin gels and triethylamine/water (TEA/H2O) binary solution both undergo a phase transition on heating. Employing differential scanning calorimetry (DSC) and isoconversional kinetic analysis, the changes upon introducing a solid surface or nanoconfining were quantified. The first system probes the effect of the addition of laponite, montmorillonite, and chitosan particles on the structure of gelatin gels. It was …

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Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt Jan 2017

Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt

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Distant metastasis of breast carcinoma reduces the five year survival rate of patients from 90% to a dismal 25%. Although the metastatic cascade has been extensively studied for decades, players that influence the progression of metastatic disease remain elusive. N-MYC and STAT Interactor (NMI) is a gene previously demonstrated by Devine et. al. to be downregulated with metastatic progression of breast cancer. However, due to the lack of a relevant genetic model, details of biological consequence of the loss of expression of this gene were unknown. We have constructed and characterized a mammary specific Nmi knock out mouse to elucidate …

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The Effects Of Incubation Environment On The Phenotype Of Hatchling Turtles: Implications For Ecology, Evolution, And Conservation, Taylor Matthew Roberge Jan 2017

The Effects Of Incubation Environment On The Phenotype Of Hatchling Turtles: Implications For Ecology, Evolution, And Conservation, Taylor Matthew Roberge

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Temperature-dependent sex determination has significant implications for the ecology, evolution, and conservation of reptiles because it can affect sex ratios, reproduction and fitness in a population. The studies presented in this dissertation characterized the impact of temperature on sex determination using both laboratory- and field-based experiments. The effects of fluctuating temperature on sex ratio, incubation duration, and hatchling phenotype were examined at 28.2 ± 5°C and 31 ± 3°C. Fluctuating incubation temperature was found to extend incubation duration, relative to constant incubation temperatures, in both cases and resulted in a significant difference in sex ratio when eggs were incubated at …

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From Despised Temporary Governor To First Elected Governor Of Louisiana: The Vindication Of William Charles Cole Claiborne, Stephanie Keller Womack Jan 2017

From Despised Temporary Governor To First Elected Governor Of Louisiana: The Vindication Of William Charles Cole Claiborne, Stephanie Keller Womack

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ABSTRACT In 1803 President Thomas Jefferson commissioned William Charles Cole Claiborne as a representative of the United States to accept the cession of the Louisiana Territory from France. After the United States took control of Louisiana on December 20, 1803, President Thomas Jefferson commissioned Claiborne as the temporary governor of the territory while Congress devised a governmental structure of the new territory and the president sought more qualified candidates for the position of governor. The inhabitants of Louisiana protested the choice of Claiborne as temporary governor, pointing to his inability to speak their language (French and Spanish), his youth (he …

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Striatal Acetylcholine And Dopamine Modulation In A Mouse Model Of Dyt1 Dystonia, Chelsea Zimmerman Jan 2017

Striatal Acetylcholine And Dopamine Modulation In A Mouse Model Of Dyt1 Dystonia, Chelsea Zimmerman

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DYT1 dystonia is a neurological movement disorder characterized by sustained muscle contractions causing twisting and repetitive movements or abnormal posture. While many movement disorders are due to loss of neurons, DYT1 dystonia does not present with any gross abnormalities. As of now, the most common form of treatment is anticholinergics. Since anticholinergic are the most effective pharmacotherapy and “paradoxical excitation” has been shown in when quinpirole, D2R agonist, is bath applied on cholinergic interneurons, we began by examining acetylcholine efflux in a DYT1 knock-in mouse model. Our studies provide evidence that at basal levels, there is a hypercholinergic state present …

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Volumetric Analysis Of The Lips In Aging African American And Caucasian Males, Matthew Steven Leftwich Jan 2017

Volumetric Analysis Of The Lips In Aging African American And Caucasian Males, Matthew Steven Leftwich

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VOLUMETRIC ANALYSIS OF THE LIPS IN AGING AFRICAN AMERICAN AND CAUCASIAN MALES DEPARTMENT OF ORTHODONTICS ABSTRACT The purpose of this cross sectional study was to analyze the volumetric changes in lip volume with respect to aging in a population of African American and Caucasian males using three-dimensional imaging technology. Materials and Methods: A sample size of 102 Caucasian males and 90 African American males with balanced faces divided into five age groups distributed as follows:[20-30], [31-40], [41-50], [51-60], [61-70[.Three-dimensional images were obtained using the 3dMDfaceTM camera system. The subjects were placed in front of the camera in natural head position …

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Behavioral Markers Of Supraspinal Pain In Clinically Relevant Models Of Spinal Cord Injury, Kathryn Yamamoto Henley Jan 2017

Behavioral Markers Of Supraspinal Pain In Clinically Relevant Models Of Spinal Cord Injury, Kathryn Yamamoto Henley

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The majority of people suffering from neuropathic pain as a result of a spinal cord injury (SCI) do not experience effective pain relief with currently available therapeutics. One aspect of preclinical studies that may be limiting the development of successful analgesics is the assessment of pain in animal models of SCI. Previous work has relied primarily on withdrawal reflexes to indicate pain; however, there is evidence that suggests this is an inadequate measure of pain sensation as spinal reflexes do not reflect the supraspinal processing of nociceptive information. The use of withdrawal responses is especially challenging in the context of …

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Electrophysiological Dynamics And Underlying Mechanisms Of Long Duration Ventricular Fibrillation, Ashleigh R. Hood Jan 2017

Electrophysiological Dynamics And Underlying Mechanisms Of Long Duration Ventricular Fibrillation, Ashleigh R. Hood

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Sudden cardiac death claims more than 300,000 lives per year in the US alone. Because it frequently goes unwitnessed, the underlying ventricular fibrillation (VF) may persist for well over 5 minutes (long duration VF, or LDVF) before attempts at defibrillation, and successful defibrillation is often followed by post-shock arrhythmias and refibrillation. The development of novel and effective therapies for LDVF, which represents a significant unmet medical need, remains largely hindered by a relatively poor understanding of the arrhythmogenic onset and maintenance of LDVF, as well as its deleterious sequelae in the context of the whole heart. Prolonged VF has been …

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Streptococcus Pneumoniae In The Heart Subvert The Host Response Through Biofilm-Mediated Resident Macrophage Killing, Anukul T. Shenoy Jan 2017

Streptococcus Pneumoniae In The Heart Subvert The Host Response Through Biofilm-Mediated Resident Macrophage Killing, Anukul T. Shenoy

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During invasive disease, blood circulating Streptococcus pneumoniae are capable of invading the heart and forming bacteria filled cardiac microlesions. These microlesions are devoid of immune cells and disruptive of cardiac functionality. While the mechanisms underlying pneumococcal invasion of the myocardium are well-described, how the heart-invaded pneumococci evade immune detection and clearance is unknown. Since its discovery in 1881, invasive pneumococcal disease has been associated with the presence of extracellular diplococci or short chains in affected tissues. Herein, we show that heart-invaded pneumococci replicate within cellular vesicles and transition into biofilms. Although the host cell permissible for intracellular replication is yet …

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Sleep Following Traumatic Brain Injury: A Qualitative Descriptive Study, Rachael Marie Mumbower Jan 2017

Sleep Following Traumatic Brain Injury: A Qualitative Descriptive Study, Rachael Marie Mumbower

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Introduction: Recent estimates suggest that as many as half of all survivors of Traumatic Brain Injury (TBI) may be experience sleep disturbances or disorders. Although quantitative research has resulted in a greater understanding of the prevalence, symptomology, and conditions associated with sleep, little is known regarding the sleep experiences of survivors of moderate-severe TBI, after their discharge from inpatient rehabilitation. The purpose of this qualitative descriptive study was to describe the sleep experiences of adults with moderate-severe TBI after rehabilitation. Methods: Qualitative descriptive inquiry was used to explore and describe sleep experiences of survivors of moderate-severe traumatic brain injury TBI …

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Modeling Mild And Repeated Mild Traumatic Brain Injury Induced Functional And Pathophysiological Alterations, Jessica Nicole Nichols Jan 2017

Modeling Mild And Repeated Mild Traumatic Brain Injury Induced Functional And Pathophysiological Alterations, Jessica Nicole Nichols

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Mild traumatic brain injury (mTBI) is a major health concern and accounts for over 75% of the 2.5 million brain injuries reported annually in the United States. Afflicted individuals typically experience a broad spectrum of physical, cognitive, and neuropsychological symptoms. Repeated mTBIs (rmTBIs) can further exacerbate these physiological alterations and negatively impact patient quality of life. Currently, there are no therapeutic agents that have successfully navigated clinical trials to be shown efficacious despite mounds of preclinical evidence suggesting to the contrary. This lack of translation exposes the dire need to design, characterize, and implement better and more relevant model systems …

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Development Of Small Molecule Inhibitors Of S. Mutans Glucosyltransferases For The Prevention Of Dental Caries, Bhavitavya Nijampatnam Jan 2017

Development Of Small Molecule Inhibitors Of S. Mutans Glucosyltransferases For The Prevention Of Dental Caries, Bhavitavya Nijampatnam

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Streptococcus mutans is the primary cariogenic agent of dental caries. This bacterium has developed numerous mechanisms to attach to tooth surfaces and initi-ate the proliferation of biofilms. In addition, S. mutans contributes to the acidification of the oral cavity, as it produces lactic acid from dietary sugars, which ensues tooth decay. Currently marketed caries therapies do not selectively kill cariogenic species, instead they disrupt the whole natural oral flora in the oral cavity including the beneficial species. In order to develop a species specific therapeutic agent, we have targeted the S. mutans glucosyltransferases (Gtfs) for our structure-based drug design. These …

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Evaluation Of Peripheral And Mucosal T Cell Phenotypes Of Chlamydia-Infected Women, Brian Makori Omwena Ogendi Jan 2017

Evaluation Of Peripheral And Mucosal T Cell Phenotypes Of Chlamydia-Infected Women, Brian Makori Omwena Ogendi

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Chlamydia trachomatis (CT) infection is the most prevalent bacterial sexually transmitted infection worldwide and women are disproportionately affected due to its reproductive complications. T cell phenotypes present during CT infection have been well characterized in the murine model, but remain to be elucidated in humans. Therefore, studies aimed at increasing our understanding of T cell phenotypes in CT-infected humans were the focus of this dissertation. The first chapter of this dissertation reviews various aspects of chlamydial infection while in the second chapter aims to address the influence of CT infection on T cell phenotypes. We first compared differences in peripheral …

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The Impact Of A Visualizing And Verbalizing Language Intervention On Reading Ability In Children With Autism Spectrum Disorders, Amy Rachel Lemelman Jan 2016

The Impact Of A Visualizing And Verbalizing Language Intervention On Reading Ability In Children With Autism Spectrum Disorders, Amy Rachel Lemelman

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Individuals with autism spectrum disorders (ASD) often exhibit deficits in language ranging from lack of functional speech to difficulties with pragmatic aspects of language. Notably, language comprehension is often impaired in individuals with ASD. Deficits in language processing frequently result in problems with reading, with the most common reading profile in children with ASD being that of adequate decoding abilities accompanied by poor comprehension. While language processing is an area of deficit, visuospatial processing is noted to be an area of strength for children with ASD. Therefore, an important question is whether a strength-oriented approach can be used to address …

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Human-Machine And Human-Human Authentication Through Active User Interaction, Manar Mohamed Jan 2016

Human-Machine And Human-Human Authentication Through Active User Interaction, Manar Mohamed

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Authentication is a fundamental security component of various critical applications. It is essential to differentiate a human user from a bot (human-machine authentication) to prevent against automated mechanisms that attack and abuse the resources of an online entity. Authentication is also essential to differentiate one human user from another (human-human authentication) to securely control the access of online accounts and computer terminals. Unfortunately, the security and usability requirements of authentication have not been adequately addressed. The current and almost universally deployed techniques, CAPTCHAs for human-machine authentication, and passwords or biometrics for human-human authentication, all suffer from numerous well-documented usability and …

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The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk Jan 2016

The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk

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Multiple sclerosis is the most common neurological disorder in young adults. Current treatments modulate the immune system, but no treatments prevent central nervous system damage. Inflammation occurs even during disease remission, contributing to ongoing damage and resulting in disease progression. The lack of neuroprotective treatments despite continued inflammatory onslaught in the central nervous system indicates the need for therapeutic discovery in this area. One potential therapeutic target is glutamate, whose dysregulation in multiple sclerosis has been implicated in excitotoxic cellular death. Herein we describe the roles of glutamate in multiple sclerosis and explore the blockade of a source of excitotoxic …

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Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge Jan 2016

Epigenetic Dysregulation In Levodopa-Induced Dyskinesia, David Anthony Figge

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Levodopa-induced dyskinesia (LID) is a persistent behavioral sensitization that develops after repeated levodopa (L-DOPA) exposure in Parkinson disease (PD) patients. LID is characterized by a “priming effect”, whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent administrations of L-DOPA. In neurons, transcriptional regulation through dynamic changes to epigenetic modifications, including DNA methylation and histone acetylation, have been shown pivotal to many long-term behavioral modifications; however, their role in LID has been minimally explored. Using a rodent model, we show LID development leads to the aberrant expression of DNA demethylating enzymes and locus-specific changes to DNA …

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Differential Effects Of Short-Term Morphine Treatment On Brain Volumes Of Men And Women With Low Back Pain, Kelsey Campbell Jan 2016

Differential Effects Of Short-Term Morphine Treatment On Brain Volumes Of Men And Women With Low Back Pain, Kelsey Campbell

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Objective: Long- and short-term opioid use is associated with morphological changes in the human brain. Opioids have analgesic and adverse effects, including addiction, that differently impact men and women. The current study aimed to investigate whether differences exist between men and women in gray matter volume changes after acute morphine treatment for chronic low back pain. Methods: This study analyzed data from 27 chronic low back pain patients (17 men, 10 women) who were treated with oral morphine over a period of 30 days. High-resolution structural images were acquired immediately before and after morphine treatment. Images were compared using voxel …

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Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell Jan 2016

Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell

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It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …

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Development Of An In Vitro, Three-Dimensional Microvasculature Model, Lauren Elizabeth Marshall Jan 2016

Development Of An In Vitro, Three-Dimensional Microvasculature Model, Lauren Elizabeth Marshall

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Vascularized in vitro models of breast cancer represent an important advance in preclinical drug testing and development. 3D in vitro tissue models are more physiologically-relevant than 2D cell culture models due to the combination of human cells and extracellular matrix (ECM) in a spatial 3D microarchitecture. Embedding a vasculature within a 3D tissue volume further increases its physiological relevance and enables paracrine cross-talk with other cell types, neovascularization and angiogenesis, size-selective permeability between blood flow and extravascular ECM, delivery of therapeutics and metabolized products to solid tumors, delivery of circulating tumor cells to metastatic sites, and production of growth-promoting and …

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Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy Jan 2016

Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy

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Understanding biological mechanisms that shape brain development and susceptibility to emotional dysfunction is crucial for generating improved treatments for depression and anxiety disorders. To study neurodevelopmental factors that influence emotionality, we use model rats that were bred for distinct behavioral responses to novelty. Rats bred for low novelty response (LRs) exhibit a high anxiety-/depressive-like phenotype compared to high novelty responder rats (HRs), which vigorously explore novelty and exhibit high impulsivity, aggression, and risk-taking. Transcriptome profiling revealed multiple gene expression differences in the early postnatal hippocampus and amygdala and in the adult amygdala of HR/LR rats. Through gene ontology analysis, we …

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Conjunctival Gene Expression And Tear Biomarkers In Atopic And Non-Atopic Keratoconus Patients Relative To Matching Controls, Erika Marie Morrow Jan 2016

Conjunctival Gene Expression And Tear Biomarkers In Atopic And Non-Atopic Keratoconus Patients Relative To Matching Controls, Erika Marie Morrow

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Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley Jan 2016

Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley

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Autoimmune and autoinflammatory diseases are a collection of disorders that are mediated by reaction of the adaptive immune system against self or commensal antigens. Altered transcription of genes involved in T cell activation and function is a key mediator of predisposition to numerous autoimmune disorders, including Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). However, we have an inadequate understanding of how the transcriptional circuits controlling these genes are dysregulated in disease. Interleukin-10 (IL-10) is cytokine with potent anti-inflammatory activity that is critical for restraining immune-mediated pathology to self-tissues. Notably, patients with nullifying mutations in IL10 develop a severe IBD …

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Energy Analysis Of Solar House Using Simulink And Trnsys, Sandeep Singh Chahal Jan 2016

Energy Analysis Of Solar House Using Simulink And Trnsys, Sandeep Singh Chahal

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As energy consumption increases it is imperative to explore techniques to address energy consumption. The objective of this study is to utilize computer modeling to estimate the total electricity consumption, the total heat load of a two-story building and solar energy generation by a photovoltaic (PV) panel located in Birmingham, AL, using an energy modeling tool called Transient System Simulation Program (TRNSYS) [1]. Simulink/MATLAB [2], a graphical programming environment, was utilized to model commonly used household appliances with a realistic schedule feeder based on daily residential usage. Next, Simulink [2] was utilized to create the model and obtain results of …

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Cultural Competence Practices Implemented In Hospitals And Health Systems By Minority Executives On The Top Management Team, John H. Cunningham Jan 2016

Cultural Competence Practices Implemented In Hospitals And Health Systems By Minority Executives On The Top Management Team, John H. Cunningham

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The study examined whether hospital implementation of cultural competence practices was influenced by the racial/ethnic composition of top management. With one-third of the U.S. population identifying with a racial or ethnic group other than non-Hispanic White, and that population continuing to grow increasingly diverse, racial and ethnic minorities are increasingly accessing health care services. Yet they represent less than 1% of the top management teams (TMT) of health care organizations. The study sought to determine the extent to which health care organizations with TMTs that are representative of the racial and ethnic compositions of the communities in which they serve …

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Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs Jan 2016

Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs

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The human cytosolic sulfotransferases (hSULTs) are a fourteen-member family of phase II drug-metabolizing enzymes that catalyze the transfer of a sulfonate moiety from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to a recipient substrate. SULT-mediated sulfation serves to deactivate physiological hormones and detoxify xenobiotics. SULT1B1 is primarily resident to the gastrointestinal tract, liver, and possibly peripheral white blood cells (WBCs), whereby it performs its supposed physiological role. The iso-form has the capacity to sulfate thyroid hormones, small phenols, and polyaromatic hy-drocarbons resulting in their inactivation, detoxification, and bioactivation/detoxification, respectively. Immunohistochemistry was used to show hSULT1B1 protein is present in periph-eral lymphocytes and neutrophils. Further, …

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Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome Jan 2016

Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome

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Parkinson disease (PD) is the most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein alpha-synuclein (α-syn). Increasing evidence points to inflammation as a chief mediator of PD with many of the inflammatory manifestations of human PD cases recapitulated in animal models of PD. We began by examining the inflammatory potential of α-syn fibrils, a newly characterized α-syn conformation that is neurotoxic and prion-like in its endogenous α-syn recruitment and cellular transmission. Our studies provide evidence that the α-syn fibrils evoke a pro-inflammatory response …

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Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien Jan 2016

Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien

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Epigenetic factors control gene expression via modulating chromatin conformation. Current studies on epigenetics mainly focus on biochemical mechanisms or functions of epigenetic factors in cancer or neurobiology. The underlying mechanism for epigenetic regulation in early embryonic development, particularly neural and neural crest development, is not well understood. In this thesis, the model organism, Xenopus laevis, is used to study epigenetic factors – polycomb repressive complex 2 (PRC2) and heterochromatin protein 1 beta (HP1β) in neural and neural crest development. In chapter one, the processes of neural and neural crest development are described, and the concepts of epigenetic mechanisms, such as …

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Methods For Analysis Of Genetic Differences In Sex And Ethnicity For Complex Human Traits, Yogasudha Veturi Veturi Jan 2016

Methods For Analysis Of Genetic Differences In Sex And Ethnicity For Complex Human Traits, Yogasudha Veturi Veturi

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In the last two decades, thousands of genome-wide association (GWA) analyses have been published. These studies have been primarily conducted using data from Caucasians and many of the reported findings have not been replicated in other populations, perhaps reflecting that the underlying architecture of effects may vary across ethnically diverse groups. Similarly, the possibility that the genetic architecture of traits may vary between males and females has also been overlooked. We propose a methodology for estimation and testing of effect heterogeneity between groups such as sex or ethnicity that involves modeling genotype-by-group random interactions. Using simulations, we show that the …

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