A5016200361- Atherosclerosis and Cardiovascular Diseases
- melanin and skin pigmentation
- Morphological variations and asymmetry
- T-cell and B-cell Immunology
- Genetic and phenotypic traits in livestock
- RNA and protein synthesis mechanisms
- Blood Pressure and Hypertension Studies
- Muscle Physiology and Disorders
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Connexins and lens biology
- Dermatological and Skeletal Disorders
- Wnt/β-catenin signaling in development and cancer
- Bacterial Genetics and Biotechnology
- IL-33, ST2, and ILC Pathways
- Myasthenia Gravis and Thymoma
- Pharmacogenetics and Drug Metabolism
- Advanced Causal Inference Techniques
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Health, Environment, Cognitive Aging
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Craniofacial Disorders and Treatments
- Hypertrophic osteoarthropathy and related conditions
- Cardiomyopathy and Myosin Studies
National Human Genome Research Institute
2023-2024
National Institutes of Health
2023-2024
University of Colorado Denver
2012-2020
University of Colorado Anschutz Medical Campus
2013-2016
University of Colorado Boulder
2010-2013
Cleveland Clinic Lerner College of Medicine
2013
Institut thématique Génétique, génomique et bioinformatique
2013
National Institute of Pathology
2008
Emory University
2006
Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a key regulator of the innate immune system, particularly in skin where, response to molecular triggers such as pathogen-associated or damage-associated patterns, NLRP1 inflammasome promotes caspase-1-dependent processing bioactive interleukin-1β (IL-1β), resulting IL-1β secretion and downstream inflammatory responses. genetically associated with risk several autoimmune diseases including generalized vitiligo, Addison disease,...
The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each us unique, distinguishable, and recognizable. Relatively little known about the genetic underpinnings normal facial variation. To address this, we carried out large genomewide association study two independent replication studies Bantu African children adolescents from Mwanza, Tanzania, region both genetically environmentally relatively homogeneous. We tested for shape...
Deep phenotyping is an emerging trend in precision medicine for genetic disease. The shape of the face affected 30-40% known syndromes. Here, we determine whether syndromes can be diagnosed from 3D images human faces.We analyzed variation three-dimensional (3D) facial 7057 subjects: 3327 with 396 different syndromes, 727 their relatives, and 3003 unrelated, unaffected subjects. We developed tested machine learning parametric approaches to automated syndrome diagnosis using images.Unrelated,...
The human face is an array of variable physical features that together make each us unique and distinguishable. Striking familial facial similarities underscore a genetic component, but little known the genes underlie shape differences. Numerous studies have estimated heritability using various methods. Here, we used advanced three-dimensional imaging technology quantitative genetics analysis to estimate narrow-sense heritability, explained by common variation, pairwise correlations 38...
Abstract Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. Aiming to define vitiligo subtypes, we discovered that age-of-onset bimodal; one-third of cases have early onset (mean 10.3 years) and two-thirds later 34.0 years). In the early-onset subgroup found novel association MHC class II region indel rs145954018, independent principal locus GWAS, represented by rs9271597; greatest was rs145954018del-rs9271597A...
Significance Vitiligo is an autoimmune disease in which spots of white skin and hair result from destruction melanocytes. associated with HLA-A*02:01 , presents multiple vitiligo melanocyte autoantigens. We localize risk to a SNP haplotype 20 kb downstream the HLA-A gene, spanning transcriptional regulatory element. Blood cells healthy subjects carrying high-risk expressed more RNA than only nonhigh-risk haplotypes. MHC class I region thus derives combined quantitative qualitative phenomena:...
Automated phenotyping is essential for the creation of large, highly standardized datasets from anatomical imaging data. Such can support large-scale studies complex traits or clinical related to precision medicine trials. We have developed a method that generates three-dimensional landmark data meet requirements standard geometric morphometric analyses. The robust and be implemented without high-performance computing resources. validated using both direct comparison manual landmarking on...
Mutation of the Caenorhabditis elegans gene unc-89 results in disorganization muscle A-bands. encodes a giant polypeptide (900 kDa) containing two protein kinase domains, PK1 and PK2. Yeast two-hybrid screening using portion UNC-89 including PK2, yielded SCPL-1 (small CTD phosphatase-like-1), which contains C terminal domain (CTD) phosphatase type domain. In addition to PK2 domain, interaction with required putative autoinhibitory sequence, immunoglobulin (Ig) fibronectin 3 (Fn3) domains...
Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as human face. The effects of growth on shape, allometry, represent a ubiquitous but poorly understood axis integration. We address question to what extent age and measures size converge single pattern allometry facial shape.Our study based two large cross-sectional cohorts children, one from Tanzania other United States (N = 7,173). employ 3D imaging geometric morphometrics relate shape...
Typically, biochemical screens that employ pure macromolecular components focus on single targets or a small number of interacting components. Researches rely whole cell for more complex systems. Bacterial DNA replicases contain multiple subunits change interactions with each stage reaction. Thus, the actual is proteins involved. It estimated overall replication reaction includes up to 100 essential targets, many suitable discovery antibacterial inhibitors. We have developed an assay, using...
Abstract Background Ribosomal protein L30 belongs to the L7Ae family of RNA-binding proteins, which recognize diverse targets. binds kink-turn motifs in 28S ribosomal RNA, pre-mRNA, and mature mRNA. has a noncanonical function as component UGA recoding machinery that incorporates selenocysteine (Sec) into selenoproteins during translation. putative motif Sec Insertion Sequence (SECIS) element 3’ UTR mammalian selenoprotein mRNAs. The SECIS also interacts with SECIS-binding 2 (SBP2), an...
The All of Us Research Program (All Us) aims to recruit over a million participants further precision medicine. Essential the verification biobanks is replication known associations establish validity. Here, we evaluated how well data replicated cigarette smoking associations.
Progressive symmetric erythrokeratoderma (PSEK) is a rare skin disorder characterised by symmetrically distributed demarcated hyperkeratotic plaques, often with associated palmoplantar hyperkeratosis, new plaques appearing over time. Most cases are inherited in an autosomal dominant manner, although few exhibit apparent recessive inheritance.To identify the gene underlying PSEK large Pakistani kindred.We first carried out autozygosity mapping using microsatellite markers candidate regions of...
Selective serotonin reuptake inhibitor (SSRI), serotonin‐norepinephrine (SNRI), and norepinephrine–dopamine (NRI) antidepressants can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study assesses the differential risks associated with commonly prescribed SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (duloxetine, venlafaxine) NRI (bupropion), as well omeprazole a reference, retrospective observational cohort in...
Reliable, inexpensive, high-throughput genotyping methods are required for clinical trials. Traditional assays require numerous enzyme digestions or too expensive large sample volumes. Our objective was to develop an efficient, and reliable assay CYP2D6 ADRB1 accounting polymorphisms including gene duplications. We utilized the multiplex SNaPshot® custom genotype method ADRB1. compared reference standards genotyped using Taqman Copy Number Variant Assay followed by pyrosequencing...
Elevated serum uric acid levels have been associated with numerous clinical phenotypes, including gout, kidney disease, and cardiovascular complications. There is conflicting evidence for the role of urate in disease (CVD) etiology symptomatology: while some studies point toward a causal acid, others suggest noncausal association. The All Us Research Program contains genomic electronic health record (EHR) data approximately 250,000 participants diverse genetic backgrounds.