A comprehensive meta-analysis of common genetic variants in autism spectrum conditions

Background Autism spectrum conditions (ASC) are a group of neurodevelopmental conditions characterized by difficulties in social interaction and communication alongside repetitive and stereotyped behaviours. ASC are heritable, and common genetic variants contribute substantial phenotypic variability. More than 600 genes have been implicated in ASC to date. However, a comprehensive investigation of candidate gene association studies in ASC is lacking. Methods In this study, we systematically reviewed the literature for association studies for 552 genes associated with ASC. We identified 58 common genetic variants in 27 genes that have been investigated in three or more independent cohorts and conducted a meta-analysis for 55 of these variants. We investigated publication bias and sensitivity and performed stratified analyses for a subset of these variants. Results We identified 15 variants nominally significant for the mean effect size, 8 of which had P values below a threshold of significance of 0.01. Of these 15 variants, 11 were re-investigated for effect sizes and significance in the larger Psychiatric Genomics Consortium dataset, and none of them were significant. Effect direction for 8 of the 11 variants were concordant between both the datasets, although the correlation between the effect sizes from the two datasets was poor and non-significant. Conclusions This is the first study to comprehensively examine common variants in candidate genes for ASC through meta-analysis. While for majority of the variants, the total sample size was above 500 cases and 500 controls, the total sample size was not large enough to accurately identify common variants that contribute to the aetiology of ASC.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Princípio republicano, cargo em comissão e clientelismo político nos municípios do estado do Rio de Janeiro: reflexões sobre a profissionalização da função pública no Brasil

A origem do comportamento orientado para a conquista de cargos públicos no Brasil remonta à formação dos primeiros povoados e vilas durante o período colonial. O nepotismo e o clientelismo político perpassam toda a história do País. Tendo como fio condutor o princípio republicano, buscou-se verificar até que ponto são os cargos em comissão utilizados no âmbito dos Municípios do Estado do Rio de Janeiro como estratégia para manter e atualizar práticas clientelísticas como o empreguismo e o nepotismo. A utilização de métodos e técnicas de análise documental e de conteúdo, em dispositivos legais produzidos pelos municípios estudados e em Relatórios de Inspeções Ordinárias neles realizadas pelo Tribunal de Contas do Estado do Rio de Janeiro, permitiu não só o proceder de uma análise qualitativa como o uso de técnicas quantitativas e representações gráficas dos achados, possibilitando uma leitura mais amena àqueles que têm pouco contato com a matéria. Essa complementaridade de métodos permitiu depreender que as ações empreendidas pelos gestores públicos, no que tange à utilização da livre nomeação, encontram-se na contramão da prática da cidadania, do igualitarismo, do respeito ao servir público. A pesquisa atestou que a quase totalidade dos municípios estudados se utiliza dos cargos em comissão de forma totalmente avessa à prevista constitucionalmente, servindo tais cargos, na verdade, para dar ingresso no serviço público a pessoas das relações do administrador, não para assessorá-lo, mas para aumentar renda familiar, cumprir compromissos de campanha e, até mesmo, para, em troca de votos, exercerem funções que por suas características deveriam ser oferecidas em concurso a toda sociedade. O estudo sugere, ao fim, um conjunto de medidas, baseadas em critérios fundamentados em princípios científicos de gestão, visando à valorização do servidor público, à redução do grau de politização da direção da administração pública e da apropriação patrimonialista dos postos de trabalho, à aceleração da profissionalização das funções públicas e a restringir o livre provimento de cargos em comissão, bem como a impingir sanções, por improbidade administrativa, aos que as desrespeitarem. Em que pese à importância de medidas preventivas, orientadas para o desenvolvimento de uma postura no sentido de um autêntico servir público, a tendência à permissividade precisa ser urgentemente afastada.

Genetic parameters for an alternative criterion to improve productive longevity of Nellore cows

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Repeatability and heritability of response to superovulation in Holstein cows

The objective of this study was to estimate the relative effects of genetic and phenotypic factors on the efficacy and efficiency of superovulation for Holstein-Friesian cows reared in Brazil. A database, established by the Associacao Brasileira de Criadores de Bovinos da Raca Holandesa, consisting of a total of 5387 superovulations of 2941 cows distributed over 473 herds and sired by 690 bulls was used for the analysis. The records were analyzed by MTDFREML (Multiple Trait Derivative-Free Restricted Maximum Likelihood), using a repeatability animal model. The fixed effects included in the model were contemporaneous group (veterinarian, herd, year and season of the superovulation); number of semen doses; cow age; and superovulation order. The estimated repeatability of the number of the transferable embryos was low (0.13), and the estimated heritability was 0.03. These results indicate that environmental factors play a critical role in the response of a cow to a superovulation treatment. There is little evidence that future responses to superovulation by individual females can be predicted by previous treatment(s) or that superovulation response is an heritable trait.

A Bayesian approach for constructing genetic maps when markers are miscoded

The advent of molecular markers has created opportunities for a better understanding of quantitative inheritance and for developing novel strategies for genetic improvement of agricultural species, using information on quantitative trait loci (QTL). A QTL analysis relies on accurate genetic marker maps. At present, most statistical methods used for map construction ignore the fact that molecular data may be read with error. Often, however, there is ambiguity about some marker genotypes. A Bayesian MCMC approach for inferences about a genetic marker map when random miscoding of genotypes occurs is presented, and simulated and real data sets are analyzed. The results suggest that unless there is strong reason to believe that genotypes are ascertained without error, the proposed approach provides more reliable inference on the genetic map.

Genetic and modifying factors that determine the risk of brain tumors

Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed. Mutagen sensivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immunosuppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well established that there is association between brain tumor risk and mutagen sensivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immunosuppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed in peripheral lymphocytes from brain tumor patients. © 2011 Bentham Science Publishers Ltd.

Genetic correlations between mature cow weight and productive and reproductive traits in Nellore cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Random regression models using Legendre polynomials or linear splines for test-day milk yield of dairy Gyr (Bos indicus) cattle

Studies investigating the use of random regression models for genetic evaluation of milk production in Zebu cattle are scarce. In this study, 59,744 test-day milk yield records from 7,810 first lactations of purebred dairy Gyr (Bos indicus) and crossbred (dairy Gyr × Holstein) cows were used to compare random regression models in which additive genetic and permanent environmental effects were modeled using orthogonal Legendre polynomials or linear spline functions. Residual variances were modeled considering 1, 5, or 10 classes of days in milk. Five classes fitted the changes in residual variances over the lactation adequately and were used for model comparison. The model that fitted linear spline functions with 6 knots provided the lowest sum of residual variances across lactation. On the other hand, according to the deviance information criterion (DIC) and Bayesian information criterion (BIC), a model using third-order and fourth-order Legendre polynomials for additive genetic and permanent environmental effects, respectively, provided the best fit. However, the high rank correlation (0.998) between this model and that applying third-order Legendre polynomials for additive genetic and permanent environmental effects, indicates that, in practice, the same bulls would be selected by both models. The last model, which is less parameterized, is a parsimonious option for fitting dairy Gyr breed test-day milk yield records. © 2013 American Dairy Science Association.

Parâmetros genéticos de escore de temperamento em bovinos da raça Nelore

Pós-graduação em Zootecnia - FCAV

Eficiência reprodutiva de fêmeas Nelore

Pós-graduação em Genética e Melhoramento Animal - FCAV

Genome-wide association study of reproduction traits in Nelore cattle, including additional phenotypic information from non-genotyped animals

Pós-graduação em Genética e Melhoramento Animal - FCAV

Respostas de populações autógamas de Avena fátua à seleção por baixas doses de diclofop-methyl e glyphosate

Pós-graduação em Agronomia (Proteção de Plantas) - FCA

Management of age at puberty in beef heifers to optimize efficiency of beef production

Age at puberty in beef heifers can influence economic efficiency of beef production through effects on both age at first calving (2 vs. 3+ years of age) and the time of conception of heifers in their initial breeding season. An overarching factor that influences age at puberty in heifers is nutritional management during both the preweaning period and between weaning and the breeding season. Age at puberty is heritable and selection for precocious puberty in populations such as the Nelore breed has the potential to substantially influence production efficiency. Highly effective hormonal technologies exist to aid in induction of puberty in well managed heifers. Age at first ovulation and pregnancy in heifers can be substantially influenced through implementation of nutritional and/or hormonal manipulation strategies. In the long term, combinations of genetic selection, nutritional strategies, and hormonal intervention when necessary will optimize efficiency of this aspect of beef production.

Osteogenesi imperfetta e Dentinogenesi imperfetta Tipo I: correlazioni cliniche e istologiche

Osteogenesis imperffecta (OI) is a heterogeneous group of heritable connetive tissue diseases, quantity and/or qualitative defect in type 1 collagen syntesis; sometimes and in some types it can be associated to dentinogenesis imperfecta (DI), a hereditary disorder in dentin formation that comprises a group of autosomal dominant genetic conditions characterized by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. Aim: the aim of this study was to assess the correlation between OI and DI from both a clinical and histological point of view, clarifying the structural and ultrastructural changes. Eighteen children (&-15 years aged) with diagnosis of OI were examined for dental alterations referable to DI; for each patient, the OI type (I, III, IV) was recorded. Extracted or normally exfolied teeth were subjected to a histological examination.Results: a total of eleven patients had abnormal discolourations referable to DI: five patients were affected by OI type I, three by OI III, and three patients by OI type IV. The discolourations, yellow/brown or oplaescent grey, could not be related to the different types of OI. Histological exam of primary teeth showed severe pathological change in dentin, structured into four diffeent layers. A collagen defect due to odontoblast dysfunction was theorized to be on the base of the histological changes. Conclusions: there is no correlation between the type of OI and the type of discolouration. The underlying dentinal defect seems to be related to an odontoblast dysfunction.