RESUMO
Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.
Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Músculos/metabolismo , Obesidade/genética , Locos de Características Quantitativas/genética , Tecido Adiposo/patologia , Adolescente , Adulto , Negro ou Afro-Americano/genética , Mapeamento Cromossômico , Diabetes Mellitus Tipo 2/patologia , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Obesidade/patologiaRESUMO
Based on its experience in implementing a rapid response system, a Level III trauma medical center recommends that other organizations (1) involve key stakeholders in the development process, (2) develop an awareness campaign, (3) hardwire the trigger response process, (4) develop quality success measures and metrics, and (5) implement a pilot and make data-driven changes accordingly.
Assuntos
Cuidados Críticos/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Cuidados Críticos/métodos , Hospitais Urbanos , Humanos , Disseminação de Informação , Estudos de Casos Organizacionais , Sudeste dos Estados UnidosRESUMO
Integrative multiomics analyses of adipose and muscle tissue transcripts, S, and genotypes revealed novel genetic regulatory mechanisms of insulin resistance in African Americans.
Assuntos
Tecido Adiposo/metabolismo , Biomarcadores/metabolismo , Negro ou Afro-Americano/genética , Regulação da Expressão Gênica , Resistência à Insulina/genética , Músculo Esquelético/metabolismo , Adolescente , Adulto , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , População Branca/genética , Adulto JovemRESUMO
Integration of retroviral elements into the host genome is a phenomena observed among many classes of retroviruses. Much information concerning the integration of retroviral elements has been documented based on in vitro analysis or expression of selectable markers. To identify possible Tf1 integration events within silent regions of the Schizosaccharomyces pombe genome, we focused on performing an in vivo genome-wide analysis of Tf1 integration events from the nonselective phase of the retrotransposition assay. We analyzed 1000 individual colonies streaked from four independent Tf1 transposed patches under nonselection conditions. Our analysis detected a population of G418(S)/neo(+) Tf1 integration events that would have been overlooked during the selective phase of the assay. Further RNA analysis from the G418(S)/neo(+) clones revealed 50% of clones expressing the neo selectable marker. Our data reveals Tf1's ability to insert within silent regions of S. pombe's genome.