Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene

The ubiquitin associated and Src-homology 3 (SH3) domain containing A (UBASH3a) is a suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis. The aim of the present study was to determine whether the UBASH3a gene influence the susceptibility to systemic lupus erythematosus (SLE) in Caucasian populations. We evaluated five UBASH3a polymorphisms (rs2277798, rs2277800, rs9976767, rs13048049 and rs17114930), using TaqMan® allelic discrimination assays, in a discovery cohort that included 906 SLE patients and 1165 healthy controls from Spain. The SNPs that exhibit statistical significance difference were evaluated in a German replication cohort of 360 SLE patients and 379 healthy controls. The case-control analysis in the Spanish population showed a significant association between the rs9976767 and SLE (Pc = 9.9E-03 OR = 1.21 95%CI = 1.07-1.37) and a trend of association for the rs2277798 analysis (P = 0.09 OR = 0.9 95%CI = 0.79-1.02). The replication in a German cohort and the meta-analysis confirmed that the rs9976767 (Pc = 0.02; Pc = 2.4E-04, for German cohort and meta-analysis, respectively) and rs2277798 (Pc = 0.013; Pc = 4.7E-03, for German cohort and meta-analysis, respectively) UBASH3a variants are susceptibility factors for SLE. Finally, a conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs9976767 polymorphism. Our results suggest that UBASH3a gene plays a role in the susceptibility to SLE. Moreover, our study indicates that UBASH3a can be considered as a common genetic factor in autoimmune diseases.

Forecasting changes in population genetic structure of alpine plants in response to global warming.

Species range shifts in response to climate and land use change are commonly forecasted with species distribution models based on species occurrence or abundance data. Although appealing, these models ignore the genetic structure of species, and the fact that different populations might respond in different ways because of adaptation to their environment. Here, we introduced ancestry distribution models, that is, statistical models of the spatial distribution of ancestry proportions, for forecasting intra-specific changes based on genetic admixture instead of species occurrence data. Using multi-locus genotypes and extensive geographic coverage of distribution data across the European Alps, we applied this approach to 20 alpine plant species considering a global increase in temperature from 0.25 to 4 °C. We forecasted the magnitudes of displacement of contact zones between plant populations potentially adapted to warmer environments and other populations. While a global trend of movement in a north-east direction was predicted, the magnitude of displacement was species-specific. For a temperature increase of 2 °C, contact zones were predicted to move by 92 km on average (minimum of 5 km, maximum of 212 km) and by 188 km for an increase of 4 °C (minimum of 11 km, maximum of 393 km). Intra-specific turnover-measuring the extent of change in global population genetic structure-was generally found to be moderate for 2 °C of temperature warming. For 4 °C of warming, however, the models indicated substantial intra-specific turnover for ten species. These results illustrate that, in spite of unavoidable simplifications, ancestry distribution models open new perspectives to forecast population genetic changes within species and complement more traditional distribution-based approaches.

Microsatellite variation reveals low genetic subdivision in a chromosome race of Sorex araneus (Mammalia, Insectivora)

Two hundred and forty-five individuals of the common shrew (Sorex araneus, Insectivora, Mammalia) from 24 sampling localities situated in four different valleys of the western European Alps were genotyped for six microsatellite loci. Allelic variability ranged from 3 to 32 different alleles at a single locus and the average gene diversity over all loci was 0.69. An analysis for F and R statistics revealed weak genetic population subdivision (Fst = 0.032; Rst = 0.016). This suggests considerable gene flow and little phylogeographic structure within and between valleys. We tested whether a stepwise mutation model (SMM) better explained variation at the microsatellite loci than an infinite allele model (IAM). No trend in favor of either model was detected.

Genetic association tests: a method for the joint analysis of family and case-control data.

With the trend in molecular epidemiology towards both genome-wide association studies and complex modelling, the need for large sample sizes to detect small effects and to allow for the estimation of many parameters within a model continues to increase. Unfortunately, most methods of association analysis have been restricted to either a family-based or a case-control design, resulting in the lack of synthesis of data from multiple studies. Transmission disequilibrium-type methods for detecting linkage disequilibrium from family data were developed as an effective way of preventing the detection of association due to population stratification. Because these methods condition on parental genotype, however, they have precluded the joint analysis of family and case-control data, although methods for case-control data may not protect against population stratification and do not allow for familial correlations. We present here an extension of a family-based association analysis method for continuous traits that will simultaneously test for, and if necessary control for, population stratification. We further extend this method to analyse binary traits (and therefore family and case-control data together) and accurately to estimate genetic effects in the population, even when using an ascertained family sample. Finally, we present the power of this binary extension for both family-only and joint family and case-control data, and demonstrate the accuracy of the association parameter and variance components in an ascertained family sample.

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

Genetic diversity and species richness patterns in Baetidae (Ephemeroptera) in the Montseny Mountain range (North-East Iberian Peninsula)

This study aimed to describe patterns of diversity of Baetidae (Ephemeroptera) at the ommunity and population levels within the Montseny Mountain range (North-East Iberian Peninsula). We studied both the distribution of 4 species of baetids in 20 sites among three catchments along the altitudinal gradient (350-1700 masl); and the genetic diversity of the mtDNA cytochrome c oxidase subunit I (cox1) gene of the two common species Baetis alpinus and Baetis rhodani. We found a gradual replacement of the dominant species along the altitudinal gradient. Baetis alpinus inhabited sites at high-altitudes, and this species was replaced by B. rhodani when the altitude decreased. Baetis melanonyx and Alainites muticus attained low abundance at all river sections, and no clear altitudinal trend appeared. Our hypothesis at the population level was that genetic structuring is associated with geographic distance and limited by drainage boundaries among the three studied catchments because of the short-time dispersion of adults. Unexpectedly, analyses of molecular variance (AMOVA) and isolation-bydistance (IBD) showed genetic diversity was unstructured by distance for both species, which may be explained by the relatively short spatial scale studied and small topographic barriers among the three catchments. The Generalized Mixed Yule-Coalescent (GMYC) model showed that B. rhodani had two differentiated genetic lineages that co-occurred in all sites. Overall, diversity of baetids was structured at the community level along the altitudinal gradient, whereas it was unstructured at the population level within the Montseny Mountain range.

Genetic diversity and species richness patterns in Baetidae (Ephemeroptera) in the Montseny Mountain range (North-East Iberian Peninsula)

This study aimed to describe patterns of diversity of Baetidae (Ephemeroptera) at the ommunity and population levels within the Montseny Mountain range (North-East Iberian Peninsula). We studied both the distribution of 4 species of baetids in 20 sites among three catchments along the altitudinal gradient (350-1700 masl); and the genetic diversity of the mtDNA cytochrome c oxidase subunit I (cox1) gene of the two common species Baetis alpinus and Baetis rhodani. We found a gradual replacement of the dominant species along the altitudinal gradient. Baetis alpinus inhabited sites at high-altitudes, and this species was replaced by B. rhodani when the altitude decreased. Baetis melanonyx and Alainites muticus attained low abundance at all river sections, and no clear altitudinal trend appeared. Our hypothesis at the population level was that genetic structuring is associated with geographic distance and limited by drainage boundaries among the three studied catchments because of the short-time dispersion of adults. Unexpectedly, analyses of molecular variance (AMOVA) and isolation-bydistance (IBD) showed genetic diversity was unstructured by distance for both species, which may be explained by the relatively short spatial scale studied and small topographic barriers among the three catchments. The Generalized Mixed Yule-Coalescent (GMYC) model showed that B. rhodani had two differentiated genetic lineages that co-occurred in all sites. Overall, diversity of baetids was structured at the community level along the altitudinal gradient, whereas it was unstructured at the population level within the Montseny Mountain range.

Random regressions models to describe the genetic variation of milk yield over multiple parities in Buffaloes

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

Estimates of genetic parameters for scrotal circumference using random regression models in Nelore cattle

A total of 15,901 scrotal circumference (SC) records from 5300 Nelore bulls, ranging from 229 to 560 days of age, were used with the objective of estimating (co)variance functions for SC, using random regression models. Models included the fixed effects of contemporary group and age of dam at calving as covariable (linear and quadratic effects). To model the population mean trend, a third order Legendre polynomial on animal age was utilized. The direct additive genetic and animal permanent environmental random effects were modeled by Legendre polynomials on animal age, with orders of fit ranging from 1 to 5. Residual variances were modeled considering 1 (homogeneity of variance) or 4 age classes. Results obtained with the random regression models were compared to multi-trait analysis. (Co)variance estimates using multi-trait and random regression models were similar. The model considering a third- and fifth-order Legendre polynomials for additive genetic and animal permanent environmental effects, respectively, was the most adequate to model changes in variance of SC with age. Heritability estimates for SC ranged from 0.24 (229 days of age) to 0.47 (300 days of age), remained almost constant until 500 days of age (0.52), decreasing thereafter (0.44). In general, the genetic correlations between measures of scrotal circumference obtained from 229 to 560 days of age decreased with increasing distance between ages. For genetic evaluation scrotal circumference could be measured between 400 and 500 days of age. (C) 2010 Elsevier B.V. All rights reserved.

Random regression models to estimate genetic parameters for test-day milk yield in Brazilian Murrah buffaloes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A cost optimization-based design of precast concrete floors using genetic algorithms

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Molecular tools and analytical approaches for the characterization of farm animal genetic diversity

Genetic studies of livestock populations focus on questions of domestication, within- and among-breed diversity, breed history and adaptive variation. In this review, we describe the use of different molecular markers and methods for data analysis used to address these questions. There is a clear trend towards the use of single nucleotide polymorphisms and whole-genome sequence information, the application of Bayesian or Approximate Bayesian analysis and the use of adaptive next to neutral diversity to support decisions on conservation.

Estimates of direct and maternal genetic effects for weights from birth to 600 days of age in Nelore cattle

Estimates of direct and maternal variance and heritability for weights at each week (up to 280 days of age) and month of age (up to 600 days of age) in Zebu cattle are presented. More than one million records on 200 000 animals, weighed every 90 days from birth to 2 years of age, were available. Data were split according to week (data sets 1) or month (data sets 2) of age at recording, creating 54 and 21 data sets, respectively. The model of analysis included contemporary groups as fixed effects, and age of dam (linear and quadratic) and age of calf (linear) effects as covariables. Random effects fitted were additive direct and maternal genetic effects, and maternal permanent environmental effect. Direct heritability estimates decreased from 0.28 at birth, to 0.12-0.13 at about 150 days of age, stayed more or less constant at 0.14-0.16 until 270 days of age and increased with age after that, up to 0.25-0.26. Maternal heritability estimates increased from birth (0.01) to a peak of 0.14 for data sets 1 and 0.07-0.08 for data sets 2 at about 180-210 days of age, before decreasing slowly to 0.07 and 0.05, respectively, at 300 days, and then rapidly diminished after 300 days of age. Permanent environmental effects were 1.5 to four times higher than genetic maternal effects and showed a similar trend.

Applying a genetic neuro-model reference adaptive controller in drilling optimization

Motivated by rising drilling operation costs, the oil industry has shown a trend toward real-time measurements and control. In this scenario, drilling control becomes a challenging problem for the industry, especially due to the difficulty associated with parameters modeling. One of the drillbit performance evaluators, the Rate Of Penetration (ROP), has been used as a drilling control parameter. However, relationships between operational variables affecting the ROP are complex and not easily modeled. This work presents a neuro-genetic adaptive controller to treat this problem. It is based on an auto-regressive with extra input signals, or ARX model and on a Genetic Algorithm (GA) to control the ROP. © [2006] IEEE.

A genetic neuro-model reference adaptive controller for petroleum wells drilling operations

Motivated by rising drilling operation costs, the oil industry has shown a trend towards real-time measurements and control. In this scenario, drilling control becomes a challenging problem for the industry, especially due to the difficulty associated to parameters modeling. One of the drill-bit performance evaluators, the Rate of Penetration (ROP), has been used in the literature as a drilling control parameter. However, the relationships between the operational variables affecting the ROP are complex and not easily modeled. This work presents a neuro-genetic adaptive controller to treat this problem. It is based on the Auto-Regressive with Extra Input Signals model, or ARX model, to accomplish the system identification and on a Genetic Algorithm (GA) to provide a robust control for the ROP. Results of simulations run over a real offshore oil field data, consisted of seven wells drilled with equal diameter bits, are provided. © 2006 IEEE.