Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and grastic cancer

Aim: To evaluate the association between polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. Methods: Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis (CG) and 160 patients with gastric cancer (GC), matched to 202 (C1) and 150 (C2) controls, respectively. Results: No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles (194Trp, 399Gln and 241Met) showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gln and XRCC3 241Met were related with gender, smoking, drinking and H pylori infection in the CG and GC groups. Conclusion: Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilian population, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

Application of Reactions Norms in Study of Genotype Environmental Interaction for Milk Yield of Buffaloes

The aim of this study was to estimate genetic parameters for milk yield (MY) in buffaloes using reaction norms. Model included the additive direct effect as random and contemporary group (herd and year of birth) were included as fixed effects and cow age classes (linear) as covariables. The animal additive direct random effect was modeled through linear Legendre polynomials on environment gradient (EG) standardized means. Mean trends were taken into account by a linear regression on Legendre polynomials of environmental group means. Residual variance was modeled trough 6 heterogeneity classes (EG). These classes of residual variance was formed : EG1: mean = 866,93 kg (621,68 kg-1011,76 kg); EG2: mean = 1193,00 kg (1011,76 kg-1251,49 kg); EG3: mean = 1309,37 kg (1251,49 kg -1393,20 kg); EG4: mean = 1497,59 kg (1393,20 kg-1593,53 kg); EG5: mean = 1664,78 kg (1593,53 kg -1727,32kg) e EG6: mean = 1973,85 kg (1727,32 kg -2422,19 kg).(Co) variance functions were estimated by restricted maximum likelihood (REML) using the GIBBS3F90 package. The heritability estimates for MY raised as the environmental gradient increased, varying from 0.20 to 0.40. However, in intermediate to favorable environments, the heritability estimates obtained with Considerable genotype-environment interaction was found for MY using reaction norms. For genetic evaluation of MY is necessary to consider heterogeneity of variances to model the residual variance.

Genetic parameters and investigation of genotype x environment interactions in Nellore x Hereford crossbred for resistance to cattle ticks in different regions of Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A unifying approach for haplotype analysis of quantitative traits in family-based association studies: Testing and estimating gene-environment interactions with complex exposure variables

We propose robust and e±cient tests and estimators for gene-environment/gene-drug interactions in family-based association studies. The methodology is designed for studies in which haplotypes, quantitative pheno- types and complex exposure/treatment variables are analyzed. Using causal inference methodology, we derive family-based association tests and estimators for the genetic main effects and the interactions. The tests and estimators are robust against population admixture and strati¯cation without requiring adjustment for confounding variables. We illustrate the practical relevance of our approach by an application to a COPD study. The data analysis suggests a gene-environment interaction between a SNP in the Serpine gene and smok- ing status/pack years of smoking that reduces the FEV1 volume by about 0.02 liter per pack year of smoking. Simulation studies show that the pro- posed methodology is su±ciently powered for realistic sample sizes and that it provides valid tests and effect size estimators in the presence of admixture and stratification.

Gene by smoking interaction in blood pressure

Hypertension (HT) is mediated by the interaction of many genetic and environmental factors. Previous genome-wide linkage analysis studies have found many loci that show linkage to HT or blood pressure (BP) regulation, but the results were generally inconsistent. Gene by environment interaction is among the reasons that potentially explain these inconsistencies between studies. Here we investigate influences of gene by smoking (GxS) interaction on HT and BP in European American (EA), African American (AA) and Mexican American (MA) families from the GENOA study. A variance component-based method was utilized to perform genome-wide linkage analysis of systolic blood pressure (SBP), diastolic blood pressure (DBP), and HT status, as well as bivariate analysis for SBP and DBP for smokers, non-smokers, and combined groups. The most significant results were found for SBP in MA. The strongest signal was for chromosome 17q24 (LOD = 4.2), increased to (LOD = 4.7) in bivariate analysis but there was no evidence of GxS interaction at this locus (p = 0.48). Two signals were identified only in one group: on chromosome 15q26.2 (LOD = 3.37) in non-smokers and chromosome 7q21.11 (LOD = 1.4) in smokers, both of which had strong evidence for GxS interaction (p = 0.00039 and 0.009 respectively). There were also two other signals, one on chromosome 20q12 (LOD = 2.45) in smokers, which became much higher in the combined sample (LOD = 3.53), and one on chromosome 6p22.2 (LOD = 2.06) in non-smokers. Neither peak had very strong evidence for GxS interaction (p = 0.08 and 0.06 respectively). A fine mapping association study was performed using 200 SNPs in 30 genes located under the linkage signals on chromosomes 15 and 17. Under the chromosome 15 peak, the association analysis identified 6 SNPs accounting for a 7 mmHg increase in SBP in MA non-smokers. For the chromosome 17 linkage peak, the association analysis identified 3 SNPs accounting for a 6 mmHg increase in SBP in MA. However, none of these SNPs was significant after correcting for multiple testing, and accounting for them in the linkage analysis produced very small reductions in the linkage signal. ^ The linkage analysis of BP traits considering the smoking status produced very interesting signals for SBP in the MA population. The fine mapping association analysis gave some insight into the contribution of some SNPs to two of the identified signals, but since these SNPs did not remain significant after multiple testing correction and did not explain the linkage peaks, more work is needed to confirm these exploratory results and identify the culprit variations under these linkage peaks. ^

Intentions: a confident-based interaction design for smart spaces

The paradigm of ubiquitous computing has become a reference for the design of Smart Spaces. Current trends in Ambient Intelligence are increasingly related to the scope of Internet of Things. This paradigm has the potential to support cost-effective solutions in the fields of telecare, e-health and Ambient Assisted Living. Nevertheless, ubiquitous computing does not provide end users with a role for proactive interactions with the environment. Thus, the deployment of smart health care services at a private space like the home is still unsolved. This PhD dissertation aims to define a person-environment interaction model to foster acceptability and users confidence in private spaces by applying the concept of user-centred security and the human performance model of seven stages of action.

Effect of environment and genotype on bread-making quality of spring-sown spring wheat cultivars in China

Improvement of end-use quality in bread wheat depends on a thorough understanding of current wheat quality and the influences of genotype (G), environment (E), and genotype by environment interaction (G x E) on quality traits. Thirty-nine spring-sown spring wheat (SSSW) cultivars and advanced lines from China were grown in four agro-ecological zones comprising seven locations during the 1998 and 1999 cropping seasons. Data on 12 major bread-making quality traits were used to investigate the effect of G, E, and G x E on these traits. Wide range variability for protein quantity and quality, starch quality parameters and milling quality in Chinese SSSW was observed. Genotype and environment were found to significantly influence all quality parameters as major effects. Kernel hardness, flour yield, Zeleny sedimentation value and mixograph properties were mainly influenced by the genetic variance components, while thousand kernel weight, test weight, and falling number were mostly influenced by the environmental variance components. Genotype, environment, and their interaction had important effects on test weight, mixing development time and RVA parameters. Cultivars originating from Zone VI (northeast) generally expressed high kernel hardness, good starch quality, but poor milling and medium to weak mixograph performance; those from Zone VII (north) medium to good gluten and starch quality, but low milling quality; those from Zone VIII (central northwest) medium milling and starch quality, and medium to strong mixograph performance; those from Zone IX (western/southwestern Qinghai-Tibetan Plateau) medium milling quality, but poor gluten strength and starch parameters; and those from Zone X (northwest) high milling quality, strong mixograph properties, but low protein content. Samples from Harbin are characterized by good gluten and starch quality, but medium to poor milling quality; those from Hongxinglong by strong mixograph properties, medium to high milling quality, but medium to poor starch quality and medium to low protein content; those from Hohhot by good gluten but poor milling quality; those from Linhe by weak gluten quality, medium to poor milling quality; those from Lanzhou by poor bread-making and starch quality; those from Yongning by acceptable bread-making and starch quality and good milling quality; and those from Urumqi by good milling quality, medium gluten quality and good starch pasting parameters. Our findings suggest that Chinese SSSW quality could be greatly enhanced through genetic improvement for targeted well-characterized production environments.

Mixed model formulations for multi-environment trials

When studying genotype X environment interaction in multi-environment trials, plant breeders and geneticists often consider one of the effects, environments or genotypes, to be fixed and the other to be random. However, there are two main formulations for variance component estimation for the mixed model situation, referred to as the unconstrained-parameters (UP) and constrained-parameters (CP) formulations. These formulations give different estimates of genetic correlation and heritability as well as different tests of significance for the random effects factor. The definition of main effects and interactions and the consequences of such definitions should be clearly understood, and the selected formulation should be consistent for both fixed and random effects. A discussion of the practical outcomes of using the two formulations in the analysis of balanced data from multi-environment trials is presented. It is recommended that the CP formulation be used because of the meaning of its parameters and the corresponding variance components. When managed (fixed) environments are considered, users will have more confidence in prediction for them but will not be overconfident in prediction in the target (random) environments. Genetic gain (predicted response to selection in the target environments from the managed environments) is independent of formulation.

Analysis of line x environment interactions for yield in navy beans. 2. Pattern analysis of lines and environment within years

Seven years of multi-environment yield trials of navy bean (Phaseolus vulgaris L.) grown in Queensland were examined. As is common with plant breeding evaluation trials, test entries and locations varied between years. Grain yield data were analysed for each year using cluster and ordination analyses (pattern analyses). These methods facilitate descriptions of genotype performance across environments and the discrimination among genotypes provided by the environments. The observed trends for genotypic yield performance across environments were partly consistent with agronomic and disease reactions at specific environments and also partly explainable by breeding and selection history. In some cases, similarities in discrimination among environments were related to geographic proximity, in others management practices, and in others similarities occurred between geographically widely separated environments which differed in management practices. One location was identified as having atypical line discrimination. The analysis indicated that the number of test locations was below requirements for adequate representation of line x environment interaction. The pattern analyses methods used were an effective aid in describing the patterns in data for each year and illustrated the variations in adaptive patterns from year to year. The study has implications for assessing the number and location of test sites for plant breeding multi-environment trials, and for the understanding of genetic traits contributing to line x environment interactions.

GGE biplot analysis of multi-environment yield trials of rice produced in a temperate climate

Low temperature is one of the main environmental constraints for rice ( Oryza sativa L.) grain production yield. It is known that multi-environment studies play a critical role in the sustainability of rice production across diverse environments. However, there are few studies based on multi-environment studies of rice in temperate climates. The aim was to study the performance of rice plants in cold environments. Four experimental lines and six cultivars were evaluated at three locations during three seasons. The grain yield data were analyzed with ANOVA, mixed models based on the best linear unbiased predictors (BLUPs), and genotype plus Genotype × Environment interaction (GGE) biplot. High genotype contribution (> 25%) was observed in grain yield and the interaction between genotype and locations was not very important. Results also showed that ‘Quila 241319’ was the best experimental line with the highest grain yield (11.3 t ha-1) and grain yield stability across the environments; commercial cultivars were classified as medium grain yield genotypes.

Evolucionismo e genética do transtorno de estresse pós-traumático

Os autores discutem, a partir do conceito evolutivo, como a resposta de estresse, nas suas possibilidades de fuga e luta e de imobilidade tônica, pode levar a uma nova compreensão etiológica do transtorno de estresse pós-traumático. Através da análise dos agrupamentos de sintomas desse diagnóstico - revivência, evitação e hiperexcitação -, procuram correlacionar os achados neurobiológicos e evolutivos. As descobertas atuais sobre a genética do transtorno de estresse pós-traumático são resumidas e colocadas nessa perspectiva evolutiva, dentro de conceitos que possibilitam o entendimento da interação gene/ambiente, como a epigenética. Propõem que a pesquisa dos fatores de risco do transtorno de estresse pós-traumático deva ser investigada do ponto de vista fatorial, onde a somatória destes aumenta o risco de desenvolvimento do quadro, não sendo possível a procura da causa do transtorno de forma única. A pesquisa de genes candidatos no transtorno de estresse pós-traumático deve levar em consideração todos os sistemas associados aos processos de respostas ao estresse, sistemas dos eixos hipotálamo-hipofisário-adrenal e simpático, mecanismos de aprendizado, formação de memórias declarativas, de extinção e esquecimento, da neurogênese e da apoptose, que envolvem vários sistemas de neurotransmissores, neuropeptídeos e neuro-hormônios.

Correlation between carbon isotope discrimination and transpiration efficiency in lines of the C-4 species Sorghum bicolor in the glasshouse and the field

Transpiration efficiency, W, the ratio of plant carbon produced to water transpired and carbon isotope discrimination of leaf dry matter, Delta(d)' were measured together on 30 lines of the C-4 species, Sorghum bicolor in the glasshouse and on eight lines grown in the field. In the glasshouse, the mean W observed was 4.9 mmol C mol(-1) H2O and the range was 0.8 mmol C mol(-1) H2O The mean Delta(d) was 3.0 parts per thousand and the observed range was 0.4 parts per thousand. In the field, the mean W was lower at 2.8 mmol C mol H2O and the mean Delta(d) was 4.6 parts per thousand. Significant positive correlations between W and Delta(d) were observed for plants grown in the glasshouse and in the field. The observed correlations were consistent with theory, opposite to those for C-4 species, and showed that variation in Delta(d) was an integrated measure of long-term variation in the ratio of intercellular to ambient CO2 partial pressure, p(i)/p(a). Detailed gas exchange measurements of carbon isotope discrimination during CO2 uptake, Delta(A) and p(i)/p(a) were made on leaves of eight S. bicolor lines. The observed relationship between Delta(A) and p(i)/p(a) was linear with a negative slope of 3.7 parts per thousand in Delta(A) for a unit change in p(i)/p(a). The slope of this linear relationship between Delta(A) and p(i)/p(a) in C-4 species is dependent on the leakiness of the CO2 concentrating mechanism of the C pathway, We estimated the leakiness (defined as the fraction of CO2 released in the bundle sheath by C-4 acid decarboxylations, which is lost by leakage) to be 0.2. We conclude that, although variation in Delta(d) observed in the 30 lines of S. bicolor is smaller than that commonly observed in C-4 species, it also reflects variation in transpiration efficiency, W. Among the eight lines examined in detail and in the environments used, there was considerable genotype x environment interaction.

The role of physiological understanding in plant breeding; From a breeding perspective

The role of physiological understanding in improving the efficiency of breeding programs is examined largely from the perspective of conventional breeding programs. Impact of physiological research to date on breeding programs, and the nature of that research, was assessed from (i) responses to a questionnaire distributed to plant breeders and physiologists, and (ii) a survey of literature abstracts. Ways to better utilise physiological understanding for improving breeding programs are suggested, together with possible constraints to delivering beneficial outcomes. Responses from the questionnaire indicated a general view that the contribution by crop physiology to date has been modest. However, most of those surveyed expected the contribution to be larger in the next 20 years. Some constraints to progress perceived by breeders and physiologists were highlighted. The survey of literature abstracts indicated that from a plant breeding perspective, much physiological research is not progressing further than making suggestions about possible approaches to selection. There was limited evidence in the literature of objective comparison of such suggestions with existing methodology, or of development and application of these within active breeding programs. It is argued in this paper that the development of outputs from physiological research for breeding requires a good understanding of the breeding program(s) being serviced and factors affecting its performance. Simple quantitative genetic models, or at least the ideas they represent, should be considered in conducting physiological research and in envisaging and evaluating outputs. The key steps of a generalised breeding program are outlined, and the potential pathways for physiological understanding to impact on these steps are discussed. Impact on breeding programs may arise through (i) better choice of environments in which to conduct selection trials, (ii) identification of selection criteria and traits for focused introgression programs, and (iii) identifying traits for indirect selection criteria as an adjunct to criteria already used. While many breeders and physiologists apparently recognise that physiological understanding may have a major role in the first area, there appears to be relatively Little research activity targeting this issue, and a corresponding bias, arguably unjustified, toward examining traits for indirect selection. Furthermore, research on traits aimed at crop improvement is often deficient because key genetic parameters, such as genetic variation in relevant breeding populations and genetic (as opposed to phenotypic) correlations with yield or other characters of economic importance, are not properly considered in the research. Some areas requiring special attention for successfully interfacing physiology research with breeding are discussed. These include (i) the need to work with relevant genetic populations, (ii) close integration of the physiological research with an active breeding program, and (iii) the dangers of a pre-defined or narrow focus in the physiological research.

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Background: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. Methods: Male OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. Results: We studied 266 males with OSA (age = 48 +/- 13y, body mass index = 29 5kg/m(2), AHI = 34 +/- 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast. the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and 11 genotype (OR = 0.27). Conclusions: Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA. (C) 2009 Elsevier B.V. All rights reserved.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.