Animal models for genetic neuromuscular diseases

The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse, both presenting significant reduction of alpha 2-laminin in the muscle and a severe phenotype. The myodystrophy mouse (Large(myd)) harbors a mutation in the glycosyltransferase Large, which leads to altered glycosylation of alpha-DG, and also a severe phenotype. Other informative models for muscle proteins include the knockout mouse for myostatin, which demonstrated that this protein is a negative regulator of muscle growth. Additionally, the stress syndrome in pigs, caused by mutations in the porcine RYR1 gene, helped to localize the gene causing malignant hypertermia and Central Core myopathy in humans. The study of animal models for genetic diseases, in spite of the existence of differences in some phenotypes, can provide important clues to the understanding of the pathogenesis of these disorders and are also very valuable for testing strategies for therapeutic approaches.

Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

Background: Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The objectives of this study were to develop a statistical method to estimate genetic parameters for macro- and micro-environmental sensitivities simultaneously, to investigate bias and precision of resulting estimates of genetic parameters and to develop and evaluate use of Akaike’s information criterion using h-likelihood to select the best fitting model. Methods: We assumed that genetic variation in macro- and micro-environmental sensitivities is expressed as genetic variance in the slope of a linear reaction norm and environmental variance, respectively. A reaction norm model to estimate genetic variance for macro-environmental sensitivity was combined with a structural model for residual variance to estimate genetic variance for micro-environmental sensitivity using a double hierarchical generalized linear model in ASReml. Akaike’s information criterion was constructed as model selection criterion using approximated h-likelihood. Populations of sires with large half-sib offspring groups were simulated to investigate bias and precision of estimated genetic parameters. Results: Designs with 100 sires, each with at least 100 offspring, are required to have standard deviations of estimated variances lower than 50% of the true value. When the number of offspring increased, standard deviations of estimates across replicates decreased substantially, especially for genetic variances of macro- and micro-environmental sensitivities. Standard deviations of estimated genetic correlations across replicates were quite large (between 0.1 and 0.4), especially when sires had few offspring. Practically, no bias was observed for estimates of any of the parameters. Using Akaike’s information criterion the true genetic model was selected as the best statistical model in at least 90% of 100 replicates when the number of offspring per sire was 100. Application of the model to lactation milk yield in dairy cattle showed that genetic variance for micro- and macro-environmental sensitivities existed. Conclusion: The algorithm and model selection criterion presented here can contribute to better understand genetic control of macro- and micro-environmental sensitivities. Designs or datasets should have at least 100 sires each with 100 offspring.

Genetic analysis on growth and carcass traits in Nelore cattle

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Heritabilities and genetic correlations for reproductive traits in an F2 reciprocal cross chicken population

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

Natural Host Relationships and Genetic Diversity of Rodent-Associated Hantaviruses in Southeastern Brazil

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

Genetic parameters for milk yield of Bubalus bubalis using unadjusted and adjusted milk production for days in milk.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genetic associations between stayability and reproductive and growth traits in Canchim beef cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genetic and environmental effects on sexual precocity traits in Nellore cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genetic analysis of visual scores and their relationships to mature female weight in Nellore breed

Dados de 79.884 animais da raça Nelore foram utilizados para estimar parâmetros genéticos e avaliar as relações entre os escores de conformação, precocidade e musculatura obtidos à desmama e ao sobreano e o peso das fêmeas à idade adulta. Utilizou-se o método da máxima verossimilhança restrita, em análise multicaracterísticas, com modelo que incluiu os efeitos genéticos aditivos direto e residual, como aleatórios, e os efeitos fixos de grupo de contemporâneos e, como covariáveis, a idade do animal à pesagem e a idade da mãe ao parto (exceto para o peso das fêmeas à idade adulta). Os grupos contemporâneos à desmama foram definidos pelas variáveis: sexo, rebanho, ano e mês de nascimento, grupo de manejo ao nascimento e à desmama. Na definição de grupo contemporâneo ao sobreano também foi incluída a variável grupo de manejo ao sobreano. Para o peso das fêmeas à idade adulta, o grupo de contemporâneos foi composto por rebanho, ano de nascimento, grupo de manejo ao sobreano, ano e estação da pesagem. Os efeitos genético materno e de ambiente permanente materno também foram incluídos no modelo para análise dos escores de conformação, precocidade e musculatura à desmama. As estimativas de herdabilidade direta obtidas foram 0,18 ± 0,02 para o escore de conformação; 0,21 ± 0,01 para o escore de precocidade; 0,22 ± 0,01 para o escore de musculatura à desmama e 0,24 ± 0,01 para o escore de conformação; 0,27 ± 0,01 para o escore de precocidade; e 0,26 ± 0,01 para o escore de musculatura ao sobreano e 0,42 ± 0,02 para o peso das fêmeas à idade adulta. As correlações genéticas estimadas entre os escores visuais medidos à desmama e ao sobreano foram positivas, variando de média a alta magnitude (0,56 ± 0,03 a 0,85 ± 0,01). Por outro lado, as correlações genéticas estimadas entre os escores visuais e o peso das fêmeas à idade adulta foram positivas e moderadas, variando de 0,21 ± 0,03 a 0,35 ± 0,03. Os resultados obtidos indicam que a seleção de animais com maiores escores visuais, principalmente ao sobreano, deve promover aumento do peso das fêmeas à idade adulta.

Milk fatty acid characterization and genetic parameter estimates for milk conjugated linoleic acid in buffaloes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Primary power distribution systems planning taking into account reliability, operation and expansion costs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Low levels of realized seed and pollen gene flow and strong spatial genetic structure in a small, isolated and fragmented population of the tropical tree Copaifera langsdorffii Desf

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

Genetic group x ambient temperature interaction effects on physiological responses and growth performance of rabbits

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

Genetic characterization of Brazilian annual Arachis species from sections Arachis and Heteranthae using RAPD markers

The genus Arachis is divided into nine taxonomic sections. Section Arachis is composed of annual and perennial species, while section Heteranthae has only annual species. The objective of this study was to investigate the genetic relationships among 15 Brazilian annual accessions from Arachis and Heteranthae using RAPD markers. Twenty-seven primers were tested, of which nine produced unique fingerprintings for all the accessions studied. A total of 88 polymorphic fragments were scored and the number of fragments per primer varied from 6 to 17 with a mean of 9.8. Two specific markers were identified for species with 2n = 18 chromosomes. The phenogram derived from the RAPD data corroborated the morphological classification. The bootstrap analysis divided the genotypes into two significant clusters. The first cluster contained all the section Arachis species, and the accessions within it were grouped based upon the presence or absence of the 'A' pair and the number of chromosomes. The second cluster grouped all accessions belonging to section Heteranthae.

Genetic relationships among Arachis hypogaea L. (AABB) and diploid Arachis species with AA and BB genomes

The cultivated peanut (Arachis hypogaea L.) is an allotetraploid, with two types of genomes, classified as AA and BB, according to cytogenetic characters. Similar genomes to those of A. hypogaea are found in the wild diploid species of section Arachis, which is one of the nine Arachis sections. The wild species have resistances to pests and diseases that affect the cultivated peanut and are a potential source of genes to increase the resistance levels in peanut. The aim of this study was to analyze the genetic variability within AA and BB genome species and to evaluate how they are related to each other and to A. hypogaea, using RAPD markers. Eighty-seven polymorphic bands amplified by ten 10-mer primers were analyzed. The species were divided into two major groups, and the AA and the BB genome species were, in general, separated from each other. The results showed that high variation is available within species that have genomes similar to the AA and the BB genomes of A. hypogaea.