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Background and aims: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language impairment, and challenges with social interaction, communication, and repetitive behaviors. Although genetics are a primary cause of ASD, the exact genes and molecular mechanisms involved in its pathogenesis are not completely clear. The FOXP2 gene encodes a transcription factor that is known for its major role in language development and severe speech problems. The present study aimed to evaluate the role of FOXP2 in ASD etiology, executive functions, and brain activities. Methods: In the present study, we recruited 450 children with ASD and 490 neurotypical control children. Three domains of executive functions (working memory, response inhibition, and vigilance) were assessed. In addition, five-minute eyes closed electroencephalography was obtained from some of the children with ASD and neurotypical children. DNA sequence and expression level of FOXP2 in blood samples of children with ASD and the control group were evaluated by using sequencing and Real-time PCR, respectively. Results: The results showed no mutations but a significant down expression of FOXP2 genes in children with ASD vs. neurotypical children. Several cognitive and executive function deficiencies were detected in children with ASD. Low alpha and gamma bands in the frontal lobe and high theta bands in the occipital lobe were revealed in children with ASD. We also found several correlations between FOXP2 expression levels and clinical assessments. Conclusions: Our finding revealed the down expression of FOXP2, which could be considered as a biomarker for ASD as well as cognitive and executive dysfunction. Based on brain mapping data, FOXP2 may be related to the theta wave abnormality of children with ASD. FOXP2 may be considered a target of novel treatment to improve memory and executive functions. Implications: Our findings highlight the role of FOXP2 mRNA level in ASD etiology, executive functions, and brain wave frequencies.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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BACKGROUND: Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia. METHODS: mRNA level of types I, II and III of NRG1 gene were studied in peripheral blood of 1540 ASD patients (IQâ¯>â¯70) and 1490 control children by quantitative Real Time PCR. Also three domains of executive functions (working memory, response inhibition and vigilance) were examined in all subjects. FINDINGS: All three types were significantly down regulated in ASD patients. Significant deficiencies in executive functions (EF) were found in ASD patients. EF deficiencies mostly were associated with down expression of mRNA level of types I and III. Also correlations were found between NRG1 expression with gender and severity of ASD symptoms. INTERPRETATIONS: Findings primarily have been suggested involvement of NRG1 in etiology of ASD. Also correlation of NRG1 mRNA level with EF deficiencies could shed lights on EF mechanisms and may suggest targeted treatments to improve particular executive functions. FUND: Young researchers and elites club funded the project due to the annual grant of special talents of Club that gave to Arvin Haghighatfard.
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Trastorno del Espectro Autista/sangre , Regulación de la Expresión Génica , Neurregulina-1/sangre , ARN Mensajero/sangre , Niño , Femenino , Humanos , Masculino , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVES: The aetiology and molecular mechanisms of schizophrenia (SCZ) and paranoid personality disorder (PPD) are not yet clarified. The present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in the aetiology and characteristics of SCZ and PPD. METHODS: mRNA levels of all genomic and mitochondrial genes which encode mitochondrial complex I subunits (44 genes) were assessed in blood in 634 SCZ, 340 PPD patients and 528 non-psychiatric subjects using quantitative real-time PCR, and associated comprehensive psychiatric, neurological and biochemical assessments. RESULTS: Significant expression changes of 18 genes in SCZ patients and 11 genes in PPD patients were detected in mitochondrial complex I. Most of these genes were novel candidate genes for SCZ and PPD. Several correlations between mRNA levels and severity of symptoms, drug response, deficits in attention, working memory, executive functions and brain activities were found. CONCLUSIONS: Deregulations of both core and supernumerary subunits of complex I are involved in the aetiology of SCZ and PPD. These deregulations have effects on brain activity as well as disorder characteristics.
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Complejo I de Transporte de Electrón/genética , Enfermedades Mitocondriales/genética , Trastorno de Personalidad Paranoide/genética , Subunidades de Proteína/genética , Esquizofrenia/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Regulación Enzimológica de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Irán , Masculino , Mitocondrias/enzimología , Mitocondrias/genética , Pruebas Neuropsicológicas , ARN Mensajero/genética , Adulto JovenRESUMEN
In this study, we provide a comparative genomic analysis of Pantoea agglomerans strain P5 and 10 closely related strains based on phylogenetic analyses. A next-generation shotgun strategy was implemented using the Illumina HiSeq 2500 technology followed by core- and pan-genome analysis. The genome of P. agglomerans strain P5 contains an assembly size of 5082485 bp with 55.4% G + C content. P. agglomerans consists of 2981 core and 3159 accessory genes for Coding DNA Sequences (CDSs) based on the pan-genome analysis. Strain P5 can be grouped closely with strains PG734 and 299 R using pan and core genes, respectively. All the predicted and annotated gene sequences were allocated to KEGG pathways. Accordingly, genes involved in plant growth-promoting (PGP) ability, including phosphate solubilization, IAA and siderophore production, acetoin and 2,3-butanediol synthesis and bacterial secretion, were assigned. This study provides an in-depth view of the PGP characteristics of strain P5, highlighting its potential use in agriculture as a biofertilizer.
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Genoma Bacteriano/genética , Genómica , Pantoea/genética , Enfermedades de las Plantas/genética , Hibridación Genómica Comparativa , Redes Reguladoras de Genes/genética , Anotación de Secuencia Molecular , Filogenia , Enfermedades de las Plantas/microbiología , Secuenciación Completa del GenomaRESUMEN
OBJECTIVE/AIM: Two major enzymes in the microRNA maturation process, Dicer and Drosha, as well as DGCR8, the assistant of Drosha, function in the microprocessor complex. In this survey, the mRNA expression profiles of Drosha, Dicer, and DGCR8 in peripheral blood mononuclear cells (PBMCs) from ankylosing spondylitis (AS) patients and healthy controls were measured. METHODS: Forty patients with AS and 40 age and gender matched healthy individuals were included in the study. PBMCs were separated, total RNA content of the cells was isolated, and first strand cDNA was synthesized. Quantitative analysis was performed through real-time PCR using the SYBR Green gene expression master mix. RESULTS: AS cases expressed the Drosha mRNA almost equal to that of healthy controls (Fold Change= -0.94; P= 0.200). However, both Dicer and DGCR8 mRNA expressions were downregulated in patients relative to healthy subjects (Fold Change= -0.54 and -0.60; P= 0.002 and 0.004, respectively). CONCLUSION: Our results suggest that downregulation of miRNA maturation components, namely Dicer and DGCR8 may be contributing in the pathogenesis procedure of AS.