RESUMEN
Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.
Asunto(s)
Trastorno Autístico/genética , Cromosomas Humanos Par 1/genética , Proteínas de Unión al ADN/genética , GTP Fosfohidrolasas/genética , Predisposición Genética a la Enfermedad , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Proteínas de Unión al ARN/genética , Factores de Transcripción/genética , Negro o Afroamericano , Pueblo Asiatico/genética , Trastorno Autístico/metabolismo , China , Estudios de Cohortes , Proteínas de Unión al ADN/metabolismo , GTP Fosfohidrolasas/metabolismo , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Proteínas de la Membrana/metabolismo , Metaanálisis como Asunto , Corteza Prefrontal/metabolismo , Proteínas de Unión al ARN/metabolismo , Riesgo , Factores de Transcripción/metabolismo , Población Blanca/genéticaRESUMEN
Mental retardation (MR) is a group of common and complex disabilities affecting the central nervous system and appears before the period of brain developmental maturity. Recently, only 40% of genetic MR has been identified, however 60% remains unexplained. In this study, we applied exome sequencing to identify the mutation p.R430X in UPF3B gene in an MR pedigree, which was validated by Sanger sequencing and completely cosegregated within this family. UPF3B gene encodes a protein involved in nonsense-mediated mRNA decay (NMD). By real-time quantitative PCR, we detected the significant difference in the mRNA expression levels of the UPF3B and the classical NMD pathway target growth arrest and DNA-damage-inducible-beta (GADD45B) between the patients and the controls. Our results directly implicated that the mutation p.R430X in UPF3B gene was the genetic etiology of the MR pedigree.
Asunto(s)
Codón sin Sentido , Exoma/genética , Predisposición Genética a la Enfermedad/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Proteínas de Unión al ARN/genética , Secuencia de Bases , China , Cromosomas Humanos X/genética , Salud de la Familia , Femenino , Expresión Génica , Humanos , Masculino , Linaje , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN/métodosRESUMEN
Silkworm silk fibers are core-shell composites of fibroin and sericin proteins. Studying the interactions between fibroin and sericin is essential for understanding the properties of these composites. It is observed that compared to the domestic silk cocoon Bombyx mori (B. mori), the adhesion between fibroin and sericin from the wild silk cocoon, Antheraea pernyi (A. pernyi), is significantly stronger with a higher degree of heterogeneity. The adsorption of A. pernyi sericin on its fibroin is almost twice the value for B. mori sericin on fibroin, both showing a monolayer Langmuir adsorption. (1)H NMR and FTIR studies demonstrate on a molecular level the stronger interactions and the more intensive complex formation between A. pernyi fibroin and sericin, facilitated by the hydrogen bonding between glycine and serine. The findings of this study may help the design of composites with superior interfacial adhesion between different components.