Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

DRD4 exon 3 variants are not associated with symptomatology of major psychoses in a German population.

Tesis para maestríaLa mejora de la educación es la estrategia prioritaria para brindar una adecuada caJidad de vida. La educación peruana solo podrá salir adelante si se actúa en los cimientos de su sistema educativo: La educación básica para que nuestros estudiantes adquieran una sólida formación integral. La tarea de mejorar la calidad educativa debe iniciarse mediante la evaluación de la institución a través de la autoevaluación. El objetivo del presente trabajo de investigación es diseñar un Programa de autoevaluación basada en la teoría de Stufflebeam para mejorar la calidad del servicio, en la Institución Educativa No 10002. Urb. Paraíso en Chiclayo. El problema de la carencia de un proceso de autoevaluación, se evidenció por la ineficacia de una adecuada gestión educativa integral que no ha posibilitado el ejercicio de este fundamental proceso. La metodología utilizada siguió diferentes etapas: la que corresponde al momento tacto perceptible, primer momento donde se realizó el diagnóstico en el contexto del objeto de estudio para comprobar la existencia del problema. En el segundo momento se realizó la revisión bibliográfica para fundamentar teóricamente -el problema. En el tercer momento se diseñó la propuesta teórica. Se aplicaron encuestas a aocentes y padres dé familia en las variables Autoevaluación -y calidad educativa. El trabajo continuó con el análisis de los resultados obtenidos mediante los instrumentos de recogida de información (cuestionarios) que se aplicaron a los docentes y padres de familia y que evidenciaron la existencia del problema. De la investigación realizada se concluyó que existe una inadecuada calidad en los servicios educativos que no ha logrado una escuela integral, lo cual podría ser superado si se aplica un Programa de autoevaluación

A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp

Background: Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the comeodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin. Objectives: To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene. Patients/Methods: The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed. Results: By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation cosegregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI. Conclusions: A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins. © 2005 British Association of Dermatologists

Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease

Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle. Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) in all five families analyzed. Mutations in CAV3 have also been described in limb-girdle muscular dystrophy type 1C (LGMD1C; refs. 6,7), demonstrating the allelism of dystrophic and non-dystrophic muscle diseases