RESUMO
Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. A total of 189 genes were significantly differentially expressed between proband-sib pairs (nominal p < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, five of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin.
Assuntos
Transtorno Autístico/genética , Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença/genética , Transcriptoma/genética , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Regulação para Baixo , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Fenótipo , Irmãos , Regulação para CimaRESUMO
Substantial evidence supports the familial aggregation of exceptional longevity. The existence of rare families demonstrating clustering for this phenotype suggests that a genetic etiology may be an important component. Previous attempts at localizing loci predisposing for exceptional longevity have been limited to association studies of candidate gene polymorphisms. In this study, a genome-wide scan for such predisposing loci was conducted by using 308 individuals belonging to 137 sibships demonstrating exceptional longevity. By using nonparametric analysis, significant evidence for linkage was noted for chromosome 4 at D4S1564 with a MLS of 3.65 (P = 0.044). The analysis was corroborated by a parametric analysis (P = 0.052). These linkage results indicate the likelihood that there exists a gene, or genes, that exerts a substantial influence on the ability to achieve exceptional old age. Identification of the genes in humans that allow certain individuals to live to extreme old age should lead to insights on cellular pathways that are important to the aging process.
Assuntos
Cromossomos Humanos Par 4/genética , Ligação Genética , Longevidade/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Feminino , Genoma Humano , Humanos , Escore Lod , Masculino , Núcleo FamiliarRESUMO
Four families highly clustered for extreme longevity are described here, representing the first report of clustering for this phenotype. Families such as these may prove to be helpful in the further understanding of the genetic contribution to achieving exceptional longevity.
Assuntos
Envelhecimento/genética , Família , Longevidade/genética , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Humanos , Masculino , FenótipoRESUMO
Nonphysician genetic counselors have been in practice only since 1971. Since that time such professional have integrated themselves into many medical settings, and established both a professional society and a certification board. Genetic counselors strive to be nondirective in their approach, allowing patients autonomy in decision making. This article will highlight some of the concepts inherent in the process of genetic counseling, as well as touch upon some of the ethical concerns faced by counselors.
Assuntos
Aconselhamento Genético/organização & administração , Descrição de Cargo , Enfermeiros Clínicos/organização & administração , Ética em Enfermagem , Humanos , Enfermeiros Clínicos/educação , Encaminhamento e ConsultaRESUMO
Exertional heat illness represents a spectrum of conditions ranging from the benign to the life-threatening. Prompt assessment and treatment can prevent fatalities in those who present as a heat casualty. More importantly, however, these injuries can be prevented from occurring altogether. This article reviews the physiology of thermoregulation and the pathophysiology of heat injuries associated with exercise. Current approaches toward the diagnosis, treatment, and prevention of exercise-induced heat injuries will also be discussed.