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Articles 31 - 60 of 118
Full-Text Articles in Life Sciences
Rna Polymerase Binding Protein A (Rbpa) Regulation Of Mycobacteria Transcription And Sensitivity To Fidaxomicin, Jerome Prusa
Rna Polymerase Binding Protein A (Rbpa) Regulation Of Mycobacteria Transcription And Sensitivity To Fidaxomicin, Jerome Prusa
Arts & Sciences Electronic Theses and Dissertations
Mycobacterium tuberculosis is the causative agent of the disease tuberculosis (TB) and remains one of the deadliest microorganisms on the planet. The effort to eradicate M. tuberculosis would benefit from the development of novel therapeutics, which requires a detailed understanding of M. tuberculosis physiology. Like all living organisms, M. tuberculosis gene expression requires transcription. Transcription in the phylum Actinobacteria, which includes mycobacteria, is unique because it includes RNA Polymerase Binding Protein A (RbpA) that is essential in both M. tuberculosis and the nonpathogenic model organism Mycobacterium smegmatis. RbpA increases the housekeeping A and housekeeping like B interactions with the RNA …
Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt
Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt
Arts & Sciences Electronic Theses and Dissertations
Cytosolic nucleic acid sensing and interferon (IFN) signaling are central to the host immune response to microbial pathogens. However, dysregulation of immunological pathways such as these can result in devastating autoimmune disease. In order to provide a robust immune response to pathogen without causing harm to self, the host immune system must engage in a delicate balancing act, interacting with microbes and determining whether they are commensal or pathogenic. The cGAS-STING pathway is a key regulator of host-microbe interactions by cytosolic nucleic sensing and IFN signaling. Loss of function in the cGAS-STING pathway leads to increased susceptibility to pathogenic threats, …
Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn
Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn
Arts & Sciences Electronic Theses and Dissertations
Neurodevelopmental disorders (NDDs) are a heterogeneous family of disorders characterized by the presence of abnormal developmental trajectories. Functional connectivity (FC) neuroimaging provides a minimally-invasive method by which to investigate the progression of these disorders and identify potential biomarkers of disease-related dysfunction for use in therapeutics’ development. My thesis work therefore took several approaches to the question of how the functional connectome reflects developmental change as well as system-wide perturbations from environmental or genetic factors. I explored the use of optical fluorescence and intrinsic signal imaging to characterize FC and stimulation-derived responses in a NDD model of perinatal exposure to selective …
Exploring The Intrinsic And Extrinsic Factors That Regulate Breast Cancer Cell Dormancy, Qihao Ren
Exploring The Intrinsic And Extrinsic Factors That Regulate Breast Cancer Cell Dormancy, Qihao Ren
Arts & Sciences Electronic Theses and Dissertations
Breast cancer can recur in patients months to decades after initial diagnosis and treatment. There is mounting evidence that dormant breast disseminated tumor cells (DTCs) exist in distant organs, whose reactivation results in cancer recurrence. However, the mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and develop cancer recurrence. Unfortunately, the extreme rarity of dormant DTCs has been the major obstacle to their study. To overcome this challenge, we developed an efficient system to isolate and study rare dormant tumor cells from metastatic organs. Using this system and single cell …
The Origins & Functional Effects Of Postzygotic Mutations Throughout The Human Lifespan, Nicole Briana Rockweiler
The Origins & Functional Effects Of Postzygotic Mutations Throughout The Human Lifespan, Nicole Briana Rockweiler
Arts & Sciences Electronic Theses and Dissertations
Mosaicism is pervasive in humans and yet we understand little of its causes and functional consequences across the lifespan. To help solve these mysteries, we developed a suite of tools, called Lachesis, to analyze postzygotic mutations (PZMs). LachesisDetect is a novel and accurate method to detect PZMs with VAFs as low as 0.04% from bulk RNA-seq samples. LachesisMap is an innovative supervised method to reconstruct postzygotic mutation phylogenies from putative prenatal PZMs. We applied Lachesis to 17,382 samples derived from 948 donors across 54 diverse tissues and cell types from the NIH’s Genotype-Tissue Expression (GTEx) project to produce the most …
Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell
Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell
Arts & Sciences Electronic Theses and Dissertations
The tumor suppressor TP53 (p53) is the most frequently mutated gene in cancer and among the most mutated genes in brain cancer. Functionally, p53 is a transcription factor that, when activated by an array of stress stimuli, regulates a complex transcriptional program that contributes to a variety of antiproliferative pathways. The loss of p53 function (LOF), either through mutation, deletion, or inhibition by alterations in the proteins that regulate p53, removes an essential barrier to the unfettered proliferation and genomic instability that drive transformation. Unlike most tumor suppressors, many p53 mutations are missense mutations that lead to stable expression of …
Precision Diffusion Imaging To Analyze Individual-Specific Plasticity, Nicole Andrea Seider
Precision Diffusion Imaging To Analyze Individual-Specific Plasticity, Nicole Andrea Seider
Arts & Sciences Electronic Theses and Dissertations
Diffusion weighted imaging (DWI) is used to non-invasively infer and characterize the structure and integrity of the brain’s white matter fibers. Individual-specific precision diffusion imaging can identify additional organizational detail important for understanding basic brain connectivity and for advancing clinical applications of DWI in neuromodulation and neurosurgical planning. The reliability of individual specific DWI and data requirements for various analytic methodologies must first be systematically assessed. The reliability and accuracy of precision diffusion imaging was evaluated as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (Chapter 2). Parameter estimation methods that allowed …
Neural Representation In The Primary Visual Cortex Amid High Neural Variability, Ji Xia
Neural Representation In The Primary Visual Cortex Amid High Neural Variability, Ji Xia
Arts & Sciences Electronic Theses and Dissertations
Animals process high-dimensional sensory information constantly. How does neural activityin sensory cortices represent this information? Recent advances in large-scale recordings allow us to monitor activity of hundreds or thousands of neurons simultaneously across a long period of time. Population recordings showed that cortical neuronal responses to repeated sensory stimulation is highly variable from trial to trial. However, how neurons in neocortex represent sensory information amid high neural variability is not well understood. To answer this question, we used two-photon calcium imaging to record from hundreds of excitatory neurons simultaneously from mouse primary visual cortex. We analyzed neural responses to repeated …
Chemical Damage To Mrna And Its Impact On Ribosome Quality-Control And Stress-Response Pathways In Eukaryotic Cells, Liewei Yan
Arts & Sciences Electronic Theses and Dissertations
Ribosome often faces defective adducts that disrupt its movement along the mRNA template. These adducts are primarily caused by chemical damage to mRNA and are highly detrimental to the decoding process on the ribosome. Hence, unless dealt with, chemical damage to RNA has been hypothesized to lead to the production of toxic protein products. Even more detrimental is the ability of damaged mRNA to drastically affect ribosome homeostasis through stalling. This in turn would lead to greatly diminished translation capacity of cells. Therefore, the inability of cells to recognize and resolve translational-stalling events is detrimental to proteostasis and could even …
Type I Interferon Regulation Of Chikungunya Virus Pathogenesis, Marissa Christine Locke
Type I Interferon Regulation Of Chikungunya Virus Pathogenesis, Marissa Christine Locke
Arts & Sciences Electronic Theses and Dissertations
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well as severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have a poor understanding of the mechanisms responsible for chronic disease. While replicating virus has not been detected in joint-associated tissues of patients with persistent arthritis nor in various animal models at convalescent time points, viral RNA is detected months after acute infection. However, there has been a lack of tools to study the mechanisms of chronic CHIKV disease. To …
The Role Of Excited States In Determining Β-Lactamase Function And Bacterial Fitness, Catherine Rae Knoverek
The Role Of Excited States In Determining Β-Lactamase Function And Bacterial Fitness, Catherine Rae Knoverek
Arts & Sciences Electronic Theses and Dissertations
Proteins are macromolecular machines that play a role in nearly every biological process. They are dynamic molecules which adopt many different conformations as they fold into their 3D structures, interact with their binding partners, and perform their functions. The most probable (lowest energy) protein conformation is referred to as the ground state, and this is often assumed to be the state determined by experimental methods such as x-ray crystallography. However, proteins also adopt higher energy excited states which can have significant probabilities. As these excited states are notoriously difficult to find and study, it is unclear if excited states contribute …
Regulation Of Transcription Factor Binding Specificity: From Binding Motifs To Local Dna Context, Jiayue Liu
Regulation Of Transcription Factor Binding Specificity: From Binding Motifs To Local Dna Context, Jiayue Liu
Arts & Sciences Electronic Theses and Dissertations
Regulation of transcription factor (TF) binding specificity lies at the heart of transcriptional control which governs how cells divide, differentiate, and respond to their environments. TFs are known to bind to DNA in a sequence specific manner, and such short sequence is known as transcription factor binding site (TFBS). However, the in vivo TF bound regions do not always contain a TFBS, and additionally, there are often excessive non-functional TFBSs with binding potential in the regulatory regions that are unbound for a given TF. This dissertation focuses on understanding the principles of TF binding specificity and is divided into two …
Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu
Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu
Arts & Sciences Electronic Theses and Dissertations
The vestibular system sense gravity and self-motion to help animals maintain body balance. Although vestibular signals inform the brain of the directions and speed of our body movements, it still remains unclear how these sensory information are processed and organized in the central nervous system. My thesis aims to illustrate neural computation underlying central vestibular tuning and the topographic organization of the vestibular circuits. First I established a novel approach to perform whole-cell recording of synaptic inputs in vivo during multi-axis movements in the central vestibular neurons. This technical advance allowed me to simultaneously measure presynaptic and postsynaptic tuning, along …
Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster
Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster
Arts & Sciences Electronic Theses and Dissertations
Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …
Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato
Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato
Arts & Sciences Electronic Theses and Dissertations
Hematopoietic stem cells (HSCs) have the unique ability to self-renew for life, to differentiate into mature blood lineages, and to readily engraft upon intravenous transplantation. As such, they are the only types of stem cells in routine clinical use. Understanding HSCs and hematopoietic development can provide many lessons for other types of stem cells as they near clinical utility. Through bone marrow transplantation, it was discovered that cells exist with regenerative potential. This led to the search to purify these cells and to determine the function of other hematopoietic cells. By isolating and transplanting cells expressing different combinations of surface …
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Arts & Sciences Electronic Theses and Dissertations
Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …
Investigating The Differentiation And Functional Maturation Of Stem Cell-Derived Β Cells, Leonardo Velazco-Cruz
Investigating The Differentiation And Functional Maturation Of Stem Cell-Derived Β Cells, Leonardo Velazco-Cruz
Arts & Sciences Electronic Theses and Dissertations
Diabetes mellitus is a chronic and global disease rapidly growing in prevalence. Diabetes can be characterized by the dysfunction or death of the glucose sensing insulin secreting cell. cells are located within the islet of Langerhans (islet), a tissue within the pancreas. Human islets are critical for the study and treatment of diabetes. However, they can only be obtained from cadaveric organ donors. These cadaveric islets do not proliferate and can only be maintained in vitro for short periods of time, making their availability rare and fleeting. Stem cell-derived -like cells can be generated in indefinite amounts and …
Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang
Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang
Arts & Sciences Electronic Theses and Dissertations
Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …
Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim
Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim
Arts & Sciences Electronic Theses and Dissertations
The ability to discern gene expression at single cell level is revolutionizing our understanding of both basic biology and human health. Peripheral nerves are essential communicators between the outside world and the CNS, as evidenced by the devastating effects of diseases that disrupt them, such as ALS, Charcot-Marie-Tooth Syndrome and diabetic neuropathy. Understanding peripheral nerve dysfunction at a mechanistic level is of considerable interest due to the increasing prevalence and associated patient care costs of these disorders. Although most research of the peripheral nerve has focused on glial-axonal interactions, the important contributions of other cell types besides Schwann cells, such …
The Evolutionary History Of Camelina Crantz (Brassicaceae) And Domestication Of The Biofuel Crop, C. Sativa (L.) Crantz, Jordan Brock
The Evolutionary History Of Camelina Crantz (Brassicaceae) And Domestication Of The Biofuel Crop, C. Sativa (L.) Crantz, Jordan Brock
Arts & Sciences Electronic Theses and Dissertations
The mustard family, Brassicaceae, is a large and economically important group of plants comprising ~350 genera and ~4060 species. Within the family, one genus, Camelina, has been neglected and nearly forgotten until recent decades. This genus comprises between 7 – 9 species, and includes Camelina sativa, an ancient oilseed crop cultivated for thousands of years in Europe. An allohexaploid, C. sativa contains high levels of omega-3 fatty acids and a seed oil composition amenable for production of aviation jet fuel. With a short generation time and ability to be cultivated on marginal soils with few inputs, C. sativa is set …
C. Elegans Response To Cadmium Toxicity, Brian James Earley
C. Elegans Response To Cadmium Toxicity, Brian James Earley
Arts & Sciences Electronic Theses and Dissertations
Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. Residing in the same group of the periodic table, cadmium and zinc share chemical characteristics that are important for their industrial uses in electroplating, batteries, pigments, and metal alloys. The similarities of ionic cadmium and zinc have significant repercussions on biological systems. While it has long been clear that cadmium is toxic to biological systems, the mechanisms of cadmium toxicity remain poorly understood. In contrast, mechanisms of zinc homeostasis have been elucidated in growing detail. In C. elegans high zinc homeostasis is regulated …
Altered Network Organization And Screen Time Use In Childhood Attention-Deficit / Hyperactivity Disorder (Adhd), Elizabeth Jane Hawkey
Altered Network Organization And Screen Time Use In Childhood Attention-Deficit / Hyperactivity Disorder (Adhd), Elizabeth Jane Hawkey
Arts & Sciences Electronic Theses and Dissertations
Introduction: Symptoms of attention-deficit/hyperactivity disorder (ADHD) have been associated with alterations in functional connectivity involving networks in the developing brain that support optimal cognitive control. However, a clear profile of altered connectivity has yet to emerge, and it remains unclear whether changes in behavioral patterns such as screen time (ST) contribute to ADHD symptomatology and altered connectivity in networks that support cognitive control. The current study examined connectivity between large-scale networks associated with cognitive control (CC), measures of executive function (EF) which index CC, and ST in children with ADHD. Methods: Our sample included 11,874 children (ages 9-11, 52% male) …
Linking Neuronal Protein Phosphatase 2a To The Dlk Stress Kinase Signaling Cascade, Margaret Hayne
Linking Neuronal Protein Phosphatase 2a To The Dlk Stress Kinase Signaling Cascade, Margaret Hayne
Arts & Sciences Electronic Theses and Dissertations
Neurons are constantly responding to internal and external cues as they adapt through signaling cascades and transcriptional programs. I have identified a role for the dual leucine zipper kinase (DLK) and the transcriptional program it controls in neuronal inhibition of the protein phosphatase PP2A. PP2A is an essential phosphatase, expressed in all cell types and required for survival. There is a reduction in PP2A activity in Alzheimer’s disease patient brains which is linked to increased phosphorylation of the microtubule associated protein Tau and ultimately cell death. Here, I have demonstrated that PP2A acts to restrain the DLK stress response and …
Testing Candidate Cerebellar Presymptomatic Biomarkers For Autism Spectrum Disorder, Zoe Wilson Hawks
Testing Candidate Cerebellar Presymptomatic Biomarkers For Autism Spectrum Disorder, Zoe Wilson Hawks
Arts & Sciences Electronic Theses and Dissertations
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed on the basis of social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar-mediated error signaling impairments contribute to the causation of ASD. However, the relationship between infant cerebellar functional connectivity (fcMRI) and later ASD behaviors and outcomes has not been investigated. Such work is critical to establish early (presymptomatic) cerebellar correlates of ASD. Methods: Data from the Infant Brain Imaging Study (n=94, 68 male) were used to evaluate cerebellar fcMRI as a presymptomatic biomarker for ASD. Specifically, brain-behavior associations were analyzed for 6-month cerebellar connections in relation …
Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker
Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker
Arts & Sciences Electronic Theses and Dissertations
People with chronic LBP display an altered movement pattern where the lumbar spine moves more readily than other joints that can contribute to the activity. The pattern is of particular clinical relevance because across multiple studies the magnitude of altered pattern is associated with LBP and function. One session of motor skill training (MST) during functional activities can improve the altered pattern. However, of the few studies investigating MST for people with LBP, none have examined the short-term or long-term effects of MST on the altered pattern. Additionally, no study has systematically examined if person-specific characteristics moderate the altered pattern …
Method Development For Enhancing Sensitivity Of Dynamic Nuclear Polarization Nuclear Magnetic Resonance Spectroscopy For Structural Studies Of Pkc-Drug Interactions, Patrick Terrence Judge
Method Development For Enhancing Sensitivity Of Dynamic Nuclear Polarization Nuclear Magnetic Resonance Spectroscopy For Structural Studies Of Pkc-Drug Interactions, Patrick Terrence Judge
Arts & Sciences Electronic Theses and Dissertations
To perform the most relevant structural studies on biological systems, experiments need to be carried out when the target proteins are in their endogenous cellular environment. Nuclear magnetic resonance (NMR) is well-suited to probe the structure and dynamics of a wide variety of systems, including biologically relevant proteins. However, NMR suffers from an inherent lack of sensitivity. Dynamic nuclear polarization (DNP) NMR is a powerful technique that is used to enhance NMR sensitivity by transferring the greater polarization of exogenously doped electron spins to nuclear spins of interest though the use of a high-power microwave source. Solid effect radicals offer …
Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell
Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell
Arts & Sciences Electronic Theses and Dissertations
Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …
Understanding Immune Responses With Single-Cell Rna Sequencing And Cytof Across Different Diseases And Model Organisms, Ekaterina Esaulova
Understanding Immune Responses With Single-Cell Rna Sequencing And Cytof Across Different Diseases And Model Organisms, Ekaterina Esaulova
Arts & Sciences Electronic Theses and Dissertations
The immune system is an integral part of a healthy functioning organism. Immune responses during the disease are complex and include the interplay of many cell subsets. Integrated genomics and bioinformatics usage can yield unique insights into the immune system’s function in health and disease at a single-cell resolution. Here we utilize complimentary single-cell profiling technologies, scRNA-seq and CyTOF, to explore immune responses across diseases and model organisms. Our approach included leveraging scRNA-seq on few samples to understand the immune response landscape and select key markers for a follow-up protein level validation using an appropriate number of replicates by FACS …
Sex Differences In The Role Of Cornichon Homolog-3 On Spatial Memory And Synaptic Plasticity, Hannah Elizabeth Frye
Sex Differences In The Role Of Cornichon Homolog-3 On Spatial Memory And Synaptic Plasticity, Hannah Elizabeth Frye
Arts & Sciences Electronic Theses and Dissertations
Cornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein highly expressed in the dorsal hippocampus (dHPC), a region where AMPARs are critical for spatial memory and synaptic plasticity. A 2016 genome-wide association study (GWAS) by Nelson et al. identified single nucleotide polymorphisms (SNPs) in the gene CNIH3 to be associated with reduced individual risk for the development of opioid use disorder (OUD) in individuals with prior opioid exposure. We previously demonstrated a key role for AMPARs in the dHPC in opioid-associated learning and memory, therefore we hypothesized that CNIH3 in the dHPC may mediate learning and memory processes through …
Analysis Of Structural Variation And Mtdna Copy Number In Finns, Liron Ganel
Analysis Of Structural Variation And Mtdna Copy Number In Finns, Liron Ganel
Arts & Sciences Electronic Theses and Dissertations
Cardiovascular disease (CVD) is a complex disease responsible for more deaths worldwide than any other cause according to the World Health Organization. Genetic association studies for CVD and related risk factors have successfully identified hundreds of loci associated with these complex diseases and traits, although much of their heritability remains unexplained. Structural variants (SVs) - including insertions, deletions, duplications, and inversions - are an understudied class of genomic variation that have the potential to explain much of the missing heritability of CVD and other complex traits. Here, we discuss advances emerging from the study of SVs in the context of …