RESUMEN
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.
Asunto(s)
Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 4/genética , Animales , Composición de Base , Secuencia de Bases , Centrómero/genética , Secuencia Conservada/genética , Islas de CpG/genética , Eucromatina/genética , Etiquetas de Secuencia Expresada , Duplicación de Gen , Variación Genética/genética , Genómica , Humanos , Datos de Secuencia Molecular , Mapeo Físico de Cromosoma , Polimorfismo Genético/genética , Primates/genética , Proteínas/genética , Seudogenes/genética , ARN Mensajero/análisis , ARN Mensajero/genética , ARN no Traducido/análisis , ARN no Traducido/genética , Recombinación Genética/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND AND OBJECTIVES: Incidence of ESKD is three times higher in black Americans than in whites, and CKD prevalence continues to rise among black Americans. Community-based kidney disease screening may increase early identification and awareness of black Americans at risk, but it is challenging to implement. This study aimed to identify participants' perspectives of community kidney disease screening. The Health Belief Model provides a theoretic framework for conceptualization of these perspectives and optimization of community kidney disease screening activities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Researchers in collaboration with the Tennessee Kidney Foundation conducted three focus groups of adults in black American churches in Nashville, Tennessee. Questions examined views on CKD information, access to care, and priorities of kidney disease health. Content analysis was used. Guided by the Health Belief Model, a priori themes were generated, and additional themes were derived from the data using an inductive approach. RESULTS: Thirty-two black Americans completed the study in 2014. Participants were mostly women (79%) with a mean age of 56 years old (range, 24-78). Two major categories of barriers to kidney disease screening were identified: (1) participant factors, including limited kidney disease knowledge, spiritual/religious beliefs, emotions, and culture of the individual; and (2) logistic factors, including lack of convenience and incentives and poor advertisement. Potential facilitators of CKD screening included provision of CKD education, convenience of screening activities, and use of culturally sensitive and enhanced communication strategies. Program recommendations included partnering with trusted community members, selecting convenient locations, tailored advertising, and provision of compensation. CONCLUSIONS: Findings of this study suggest that provider-delivered culturally sensitive education and stakeholder engagement are critical to increase trust, decrease fear, and maximize participation and early identification of kidney disease among black Americans considering community screening.
Asunto(s)
Negro o Afroamericano , Servicios de Salud Comunitaria , Conocimientos, Actitudes y Práctica en Salud/etnología , Enfermedades Renales/diagnóstico , Adulto , Publicidad , Negro o Afroamericano/psicología , Anciano , Competencia Cultural , Emociones , Femenino , Grupos Focales , Educación en Salud , Accesibilidad a los Servicios de Salud , Humanos , Enfermedades Renales/economía , Enfermedades Renales/etnología , Masculino , Persona de Mediana Edad , Motivación , Religión , Confianza , Adulto JovenRESUMEN
CRISPR-Cas9 technology has accelerated biological research becoming routine for many laboratories. It is rapidly replacing conventional gene editing techniques and has high utility for both genome-wide and gene-focussed applications. Here we present the first individually cloned CRISPR-Cas9 genome wide arrayed sgRNA libraries covering 17,166 human and 20,430 mouse genes at a complexity of 34,332 sgRNAs for human and 40,860 sgRNAs for the mouse genome. For flexibility in generating stable cell lines the sgRNAs have been cloned in a lentivirus backbone containing PiggyBac transposase recognition elements together with fluorescent and drug selection markers. Over 95% of tested sgRNA induced specific DNA cleavage as measured by CEL-1 assays. Furthermore, sgRNA targeting GPI anchor protein pathway genes induced loss of function mutations in human and mouse cell lines measured by FLAER labelling. These arrayed libraries offer the prospect for performing screens on individual genes, combinations as well as larger gene sets. They also facilitate rapid deconvolution of signals from genome-wide screens. This set of vectors provide an organized comprehensive gene editing toolbox of considerable scientific value.