Genetic studies of osteoporosis: A rethink required

It has been 10 years since the seminal paper by Morrison and colleagues reporting the association of alleles of the vitamin D receptor and bone density [1], a paper which arguably kick-started the study of osteoporosis genetics. Since that report there have been literally thousands of osteoporosis genetic studies published, and large numbers of genes have been reported to be associated with the condition [2]. Although some of these reported associations are undoubtedly true, this snow-storm of papers and abstracts has clouded the field to such a great extent that it is very difficult to be certain of the veracity of most genetic associations reported hereto. The field needs to take stock and reconsider the best way forward, taking into account the biology of skeletal development and technological and statistical advances in human genetics, before more effort and money is wasted on continuing a process in which the primary achievement could be said to be a massive paper mountain. I propose in this review that the primary reasons for the paucity of success in osteoporosis genetics has been: •the absence of a major gene effect on bone mineral density (BMD), the most commonly studied bone phenotype; •failure to consider issues such as genetic heterogeneity, gene–environment interaction, and gene–gene interaction; •small sample sizes and over-optimistic data interpretation; and •incomplete assessment of the genetic variation in candidate genes studied.

Genetic determinants of bone density and fracture risk: State of the art and future directions

Context: Osteoporosis is a common, highly heritable condition that causes substantial morbidity and mortality, the etiopathogenesis of which is poorly understood. Genetic studies are making increasingly rapid progress in identifying the genes involved. Evidence Acquisition and Synthesis: In this review, we will summarize the current understanding of the genetics of osteoporosis based on publications from PubMed from the year 1987 onward. Conclusions: Most genes involved in osteoporosis identified to date encode components of known pathways involved in bone synthesis or resorption, but as the field progresses, new pathways are being identified. Only a small proportion of the total genetic variation involved in osteoporosis has been identified, and new approaches will be required to identify most of the remaining genes.

CIMMYT-selected derived synthetic bread wheats for rainfed environments: Yield evaluation in Mexico and Australia.

Synthetic backcrossed-derived bread wheats (SBWs) from CIMMYT were grown in the Northwest of Mexico at Centro de Investigaciones Agrícolas del Noroeste (CIANO) and sites across Australia during three seasons. During three consecutive years Australia received “shipments” of different SBWs from CIMMYT for evaluation. A different set of lines was evaluated each season, as new materials became available from the CIMMYT crop enhancement program. These consisted of approximately 100 advanced lines (F7) per year. SBWs had been top and backcrossed to CIMMYT cultivars in the first two shipments and to Australian wheat cultivars in the third one. At CIANO, the SBWs were trialled under receding soil moisture conditions. We evaluated both the performance of each line across all environments and the genotype-by-environment interaction using an analysis that fits a multiplicative mixed model, adjusted for spatial field trends. Data were organised in three groups of multienvironment trials (MET) containing germplasm from shipment 1 (METShip1), 2 (METShip2), and 3 (METShip3), respectively. Large components of variance for the genotype × environment interaction were found for each MET analysis, due to the diversity of environments included and the limited replication over years (only in METShip2, lines were tested over 2 years). The average percentage of genetic variance explained by the factor analytic models with two factors was 50.3% for METShip1, 46.7% for METShip2, and 48.7% for METShip3. Yield comparison focused only on lines that were present in all locations within a METShip, or “core” SBWs. A number of core SBWs, crossed to both Australian and CIMMYT backgrounds, outperformed the local benchmark checks at sites from the northern end of the Australian wheat belt, with reduced success at more southern locations. In general, lines that succeeded in the north were different from those in the south. The moderate positive genetic correlation between CIANO and locations in the northern wheat growing region likely reflects similarities in average temperature during flowering, high evaporative demand, and a short flowering interval. We are currently studying attributes of this germplasm that may contribute to adaptation, with the aim of improving the selection process in both Mexico and Australia.

Produtividade, adaptabilidade e estabilidade fenotípica de cultivares de tomateiro sob diferentes condições de ambiente

O objetivo deste trabalho foi estudar o desempenho produtivo, adaptabilidade e estabilidade fenotípica de seis genótipos de tomateiro na região de Marília, SP. Os experimentos foram conduzidos em nove ambientes (seis sob condições de cultivo protegido e três sob condições de céu aberto), com seis genótipos (Carmen, Diva, Donador, Graziela, Vita e HE-295), em blocos casualizados, com quatro repetições. Ocorreram diferenças significativas entre ambientes, e a média geral dos cultivos protegidos superou a dos cultivos a céu aberto quanto à produtividade, apesar de a média geral dos cultivos a céu aberto ser superior quanto ao peso médio de frutos. As cultivares, à exceção de HE-295, demonstraram alta estabilidade, merecendo destaque as cultivares Carmen, Donador e Vita, que tiveram rendimento médio superior ao da média geral, adaptabilidade geral e comportamento previsível em todos os ambientes estudados. Quanto ao peso médio dos frutos, as cultivares Diva e Vita foram as únicas que mostraram ampla adaptabilidade a todos os ambientes, comportamento previsível, além de apresentarem peso médio do fruto superior ao da média geral.

Efeito da interação genótipo × ambiente sobre o peso ao nascimento, aos 205 e aos 550 dias de idade de bovinos da raça Nelore na Região Sul do Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Testes multiambientais na seleção de genótipos de arroz utilizando o modelo de regressão nos sítios ou locais

A análise da interação genótipo x ambiente utilizda no melhoramento de plantas tem sofrido mudanças na última década, melhorando a sua eficiência quanto à seleção dos genótipos sob diferentes condições ambientais. O objetivo deste trabalho foi analisar a produtividade e estabilidade de 12 genótipos de arroz em oito ambientes, durante os anos 2005 e 2006, na Colômbia. O delineamento utilizado foi o de blocos ao acaso com quatro repetições. Os parâmetros de estabilidade fenotípica e o agrupamento dos ambientes foram estimados pelo estudo da interação genótipo x ambiente, segundo o método SREG (Regressão nos sítios ou locais) e seu gráfico biplot (GGE). As análises estatísticas indicaram diferenças significativas (com 5% de probabilidade de erro) entre genótipos e entre ambientes e significância (com 5% de probabilidade de erro) da interação genótipo x ambiente, sugerindo uma resposta diferente dos genótipos nos vários ambientes. No método SREG, os dois primeiros componentes principais da interação explicaram 75,29% da interação. Os genótipos 400094, 350361 e a variedade Fedearroz 50 foram considerados os de maior produtividade. Segundo o gráfico biplot GGE, os ambientes La Libertad e Escobal foram os mais favoráveis para o cultivo do arroz.

Efeito da interação reprodutor x rebanho sobre as produções de leite e de gordura na raça Pardo-Suíça

Dados de 4.959 lactações de 2.414 vacas da raça Pardo-Suíça, filhas de 70 reprodutores, distribuídos em 51 rebanhos, foram utilizados para se estimar o componente de variância para a interação reprodutor x rebanho das produções de leite e de gordura e verificar o efeito desta interação sobre a avaliação genética dos reprodutores, por meio de modelos que diferiam na presença e ausência do termo de interação. As produções de leite e de gordura foram ajustadas para duas ordenhas diárias, 305 dias de lactação e idade adulta da vaca. O teste da razão de verossimilhança foi utilizado na verificação da efetividade da inclusão da interação no modelo. As médias das produções de leite e de gordura foram 6085,79 ± 1629,73 kg e 225,61 ± 60,44 kg, respectivamente. A proporção da variância total decorrente da interação reprodutor x rebanho foi 0,4%, para a produção de leite, e 1%, para a produção de gordura. A estimativa de herdabilidade foi 0,38, para a produção de leite, utilizando-se ambos os modelos, e reduziu de 0,40 para 0,39, para a produção de gordura, quando o modelo com interação foi considerado. A função de verossimilhança aumentou significativamente com a inclusão da interação no modelo. A correlação de Spearman foi próxima de um para ambas as características, quando todos os reprodutores foram considerados. Houve redução de 1% na estimativa de acurácia dos valores genéticos preditos para ambas as características, porém, a correlação de Pearson estimada entre as acurácias obtidas para cada modelo estudado foi próxima à unidade. A interaçãoreprodutor x rebanho não afetou as estimativas de componentes de variâncias genética e residual e a ordem de classificação dos reprodutores para ambas as características.

Variance heterogeneity for milk yield in Brazilian and Colombian Holstein herds

Heterogeneity of variances for milk yield (MY) was determined for Brazilian and Colombian herds. The herds were grouped as high or low variability within each country, using as criterion the phenotypic standard deviation (PSD) of MY in the contemporary groups of cows, from the first to the sixth calving. Brazilian and Colombian herds with PSD greater than 1,168 kg or 1,012 kg, respectively, were classified as high variability while the herd groups with values lower than those were classified as low variability. The genetic parameters for MY within each herd group were estimated using bivariate analysis in an animal model and the restricted maximum likelihood method with a derivative free algorithm, using 72,280 first lactations of cows, daughters of 1,880 sires. Heterogeneous variances were found, and Brazilian herds with high PSD had the greatest additive and residual genetic variances and heritability coefficients for MY. MY genetic correlation coefficients between herds of high and low variability within each country were 0.96 and 0.93 while between countries they varied from 0.72 to 0.81, suggesting that there was a reclassification of animals in the two countries and also heterogeneity of variances. This phenomenon leads to the questioning of the strategy of imported semen usage and the need to do genetic evaluations to identify sires with greater genetic potential for (sub) tropical environmental conditions.

Phenotypic plasticity of composite beef cattle performance using reaction norms model with unknown covariate

The objective of the present study was to determine the presence of genotype by environment interaction (G × E) and to characterize the phenotypic plasticity of birth weight (BW), weaning weight (WW), postweaning weight gain (PWG) and yearling scrotal circumference (SC) in composite beef cattle using the reaction norms model with unknown covariate. The animals were born between 1995 and 2008 on 33 farms located throughout all Brazilian biomes between latitude -7 and -31, longitude -40 and -63. The contemporary group was chosen as the environmental descriptor, that is, the environmental covariate of the reaction norms. In general, higher estimates of direct heritability were observed in extreme favorable environments. The mean of direct heritability across the environmental gradient ranged from 0.05 to 0.51, 0.09 to 0.43, 0.01 to 0.43 and from 0.12 to 0.26 for BW, WW, PWG and SC, respectively. The variation in direct heritability observed indicates a different response to selection according to the environment in which the animals of the population are evaluated. The correlation between the level and slope of the reaction norm for BW and PWG was high, indicating that animals with higher average breeding values responded better to improvement in environmental conditions, a fact characterizing a scale of G × E. Low correlation between the intercept and slope was obtained for WW and SC, implying re-ranking of animals in different environments. Genetic variation exists in the sensitivity of animals to the environment, a fact that permits the selection of more plastic or robust genotypes in the population studied. Thus, the G × E is an important factor that should be considered in the genetic evaluation of the present population of composite beef cattle. © The Animal Consortium 2012.

Exploring the multifactorial nature of autism through computational systems biology: Calcium and the Rho GTPase RAC1 under the spotlight

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca2+) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism. © 2013 Springer Science+Business Media New York.

Selecting for rust (Puccinia psidii) resistance in Eucalyptus grandis in São Paulo State, Brazil

In Brazil, Eucalyptus grandis is a key species for wood production. However, some genotypes are susceptible to rust (Puccinia psidii), mainly in São Paulo State, where climatic conditions are favorable for its development. Rust represents a high economic risk to forest companies because of the high potential of damage to commercial eucalypt plantations. The aims of the present study were (i) to select progenies of E. grandis for stability and adaptability regarding resistance to rust at different locations; (ii) compare the selections under these different climatic conditions; and (iii) compare rust severity in the field with the theoretical model. We observed that climatic conditions were extremely influential factors for rust development, but even under favorable conditions for disease development, we found rust-resistant progenies. In sites unfavorable for rust development, we detected highly susceptible progenies. We found significant correlation among the genetic material, environmental conditions and disease symptoms, however, we observed a simple genotype-environmental interaction and significant genetic variability among the progenies. The average heritability was high among the progenies in all sites, indicating substantial genetic control for rust resistance. We also observed a good relationship between rust severity in the field and the theoretical model that considered annual average temperature and leaf wetness. © 2013 Elsevier B.V.

Interação genótipo ambiente para perímetro escrotal em bovinos da raça Nelore utilizando normas de reação

Pós-graduação em Zootecnia - FCAV

Interação genótipo-ambiente em características de crescimento de bovinos da raça Nelore

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Interação genótipo – ambiente no peso ao sobreano na raça Nelore

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

Interação genótipo-ambiente para a produção de leite em bubalinos no Brasil e na Colômbia

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