Genetic heterogeneity in erythropoietic protoporphyria: a study of the enzymatic defect in nine affected families

Erythropoietic protoporphyria (EPP) is associated with a deficiency of protohaem ferrolyase. We have used a novel assay for this enzyme based on its ability to utilize zinc as a substrate to investigate the inheritance of EPP in nine affected families. Zinc chelatase activity was markedly reduced in peripheral blood mononuclear cells from 14 EPP patients (mean, 3.3 nmol Zn protohaem/h/mg protein; range, 0.3-8.0) when compared with 41 controls (16.8 +/- 3.6) p less than 0.01. In three families with parent-to-child transmission of disease, the asymptomatic parent had an enzymatic activity within the normal range. In three pedigrees where the parents were asymptomatic, enzymatic activities were below the 95% confidence limits in both. Zinc chelatase activity was below the mean control value in 17 of the 18 parents in nine affected pedigrees, and six of seven asymptomatic offspring of patients with protoporphyria. The findings suggest that EPP is not transmitted as a simple dominant trait and that inheritance of more than one gene may be required for disease expression.

Cashew cultivation, access to land and food security in Brong-Ahafo Region, Ghana: Preventing the intergenerational transmission of poverty

This research aimed to investigate the implications of changing agricultural land use from food production towards increased cashew cultivation for food security and poverty alleviation in Jaman North District, Brong-Ahafo Region of Ghana. Based on qualitative, participatory research with a total of 60 participants, the research found that increased cashew production had led to improvements in living standards for many farmers and their children over recent years. Global demand for cashew is projected to continue to grow rapidly in the immediate future and cashew-growing areas of Ghana are well placed to respond to this demand. Cashew farmers however were subject to price fluctuations in the value of Raw Cashew Nuts (RCN) due to unequal power relations with intermediaries and export buyer companies and global markets, in addition to other vulnerabilities that constrained the quality and quantity of cashew and food crops they could produce. The expansion of cashew plantations was leading to pressure on the remaining family lands available for food crop production, which community members feared could potentially compromise the food security of rural communities and the land inheritance of future generations.

Transgenerational, dynamic methylation of stomata genes in response to low relative humidity

Transgenerational inheritance of abiotic stress-induced epigenetic modifications in plants has potential adaptive significance and might condition the offspring to improve the response to the same stress, but this is at least partly dependent on the potency, penetrance and persistence of the transmitted epigenetic marks. We examined transgenerational inheritance of low Relative Humidity-induced DNA methylation for two gene loci in the stomatal developmental pathway in Arabidopsis thaliana and the abundance of associated short-interfering RNAs (siRNAs). Heritability of low humidity-induced methylation was more predictable and penetrative at one locus (SPEECHLESS, entropy ≤ 0.02; χ2 < 0.001) than the other (FAMA, entropy ≤ 0.17; χ2 ns). Methylation at SPEECHLESS correlated positively with the continued presence of local siRNAs (r2 = 0.87; p = 0.013) which, however, could be disrupted globally in the progeny under repeated stress. Transgenerational methylation and a parental low humidity-induced stomatal phenotype were heritable, but this was reversed in the progeny under repeated treatment in a previously unsuspected manner.

Breeding biology, adult survival and territoriality of the white-browed treecreeper (climacteris affinis) in north-west Victoria, Australia

This is the first study to present empirical data describing the social organisation and breeding biology of the White-browed Treecreeper (Climacteris affinis). The species is typical of many small Australian passerines in that it has high annual survival (~80%), small clutches (mean = 1.95 ± 0.05), long breeding seasons (eggs laid August to November) and long incubation (17–18 days) and nestling periods (25–26 days), corrected for body weight. Reproductive effort is modified in response to variation in climatic conditions by adjusting the commencement of breeding and number of clutches laid per season, which is facilitated by an extended breeding season. White-browed Treecreepers occupied relatively large (mean = 8.4 ± 0.8 ha), all-purpose territories throughout the year. However, unlike many group territorial birds, territory size was not related to the number of occupants. The role of food limitation and climatic variability in relation to territory dispersion and life-history traits is explored. Facultative cooperative breeding was confirmed. Cooperative groups were formed through male philopatry, with usually only one, but up to three, male helpers present in a moderate fraction (35%) of breeding units. Thus, all species of Climacteris are now confirmed as facultative cooperatively breeding species, which provides further evidence for the aggregation of cooperative breeders at the generic level in mixed (i.e. cooperative and pair breeders) phylogenetic clades. In C. affinis, males may attain breeding positions through inheritance of their natal territory or by filling vacancies in nearby territories. Females obtained breeding positions by ‘floating’ as non-breeding residents in established territories, waiting for a vacancy to arise.

Communicating climate change: public responsiveness and matters of concern

Since climate change captured global attention in the 1990s, the private individual, addressed as a member of a concerned public, has occupied a focal position in the discourse of environmental amelioration. Recently, a range of prominent books, films and television programs — for example, Tim Flannery’s The Weather Makers (2005), Al Gore’s An Inconvenient Truth (2006) and ABC TV’s Carbon Cops (2007) — have promoted the role of the individual as the ‘starting point’ for effective environmental action. These texts assume that the provision and comprehension of sufficient information to the public about climate change will change individual habits and practices. This accords with the ‘information-deficit model’ in environmental communication research, a concept that asserts a direct connection between individual awareness and response, and collective action. This paper discusses the limitations of this model, pervasive in both popular and official approaches to climate change. It will interrogate the philosophical assumptions that underlie it, in which nature and culture are polarised and the human is positioned in a certain, and separate, relationship to the non-human world — an inheritance of the very logic that enables the continued exploitation of nature. Applying Bruno Latour’s notion of a ‘matter of concern’ to climate change, where the gathering of a range of irreducible forces and im/materialities continually produce these phenomena, this paper proposes that, in thinking about climate change as essentially unrepresentable, a different mode of public engagement with the issue is asserted.

Effects of early-life environment and epigenetics on cardiovascular disease risk in children: highlighting the role of twin studies

Cardiovascular disease (CVD) is the leading cause of death worldwide and originates in early life. The exact mechanisms of this early-life origin are unclear, but a likely mediator at the molecular level is epigenetic dysregulation of gene expression. Epigenetic factors have thus been posited as the likely drivers of early-life programming of adult-onset diseases. This review summarizes recent advances in epidemiology and epigenetic research of CVD risk in children, with a particular focus on twin studies. Classic twin studies enable partitioning of phenotypic variance within a population into additive genetic, shared, and nonshared environmental variances, and are invaluable in research in this area. Longitudinal cohort twin studies, in particular, may provide important insights into the role of epigenetics in the pathogenesis of CVD. We describe candidate gene and epigenome-wide association studies (EWASs) and transgenerational epigenetic inheritance of CVD, and discuss the potential for evidence-based interventions. Identifying epigenetic changes associated with CVD-risk biomarkers in children will provide new opportunities to unravel the underlying biological mechanism of the origins of CVD and enable identification of those at risk for early-life interventions to alter the risk trajectory and potentially reduce CVD incidence later in life.

Exploratory semiparametric analysis of two-dimensional diffusions in finance

We examine bivariate extensions of Aït-Sahalia’s approach to the estimation of univariate diffusions. Our message is that extending his idea to a bivariate setting is not straightforward. In higher dimensions, as opposed to the univariate case, the elements of the Itô and Fokker-Planck representations do not coincide; and, even imposing sensible assumptions on the marginal drifts and volatilities is not sufficient to obtain direct generalisations. We develop exploratory estimation and testing procedures, by parametrizing the drifts of both component processes and setting restrictions on the terms of either the Itô or the Fokker-Planck covariance matrices. This may lead to highly nonlinear ordinary differential equations, where the definition of boundary conditions is crucial. For the methods developed, the Fokker-Planck representation seems more tractable than the Itô’s. Questions for further research include the design of regularity conditions on the time series dependence in the data, the kernels actually used and the bandwidths, to obtain asymptotic properties for the estimators proposed. A particular case seems promising: “causal bivariate models” in which only one of the diffusions contributes to the volatility of the other. Hedging strategies which estimate separately the univariate diffusions at stake may thus be improved.

Genetics of resistance to powdery mildew (Microsphaera diffusa) in Brazilian soybean populations

Crosses between resistant and susceptible soybean cultivars were performed and the F2 populations were obtained to study the inheritance of soybean resistance to powdery mildew and to estimate the number and action of genes related to resistance. The reaction to powdery mildew was studied in a greenhouse and pots carrying plants with symptoms were distributed among the pots carrying the genotypes to be tested as a source of inoculum. Individual plants were scored according to the method of Yorinori (1997), with modifications, and classified as resistant or susceptible. The results showed that adult soybeans plants can present resistance to powdery mildew, which is controlled by one major gene with a dominant effect.

Interactions between genetic predisposition and environmental toxicants for development of lung cancer

Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However. mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes is strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (> 30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (< 30 pack-years), the genetic predisposition plays on important role For the risk (odds ratio = 3.46; 95% CL = 0.46-40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variations in cancer outcome, to identify high risk individuals and to assess health risk. (C) 1997 Wiley Liss, Inc.

Identification of QTLs associated with citrus resistance to Phytophthora gummosis

Citrus gummosis, caused by Phylophthora spp., is an important citrus disease in Brazil. Almost all citrus rootstock varieties are susceptible to it to some degree, whereas resistance is present in Poncirus trifoliata, a closely related species. The objective of this study was to detect QTLs linked to citrus Phylophthora gummosis resistance. Eighty individuals of the F, progeny, obtained by controlled crosses between Sunki mandarin Citrus sunki (susceptible) and Poncirus trifoliata cv. Rubidoux (resistant), were evaluated. Resistance to Phytophthora parasitica was evaluated by inoculating stems of young plants with a disc of fungal mycelia and measuring lesion lengths a month later. Two QTLs linked to gummosis resistance were detected in linkage groups I and 5 of the P. trifoliala map, and one QTL in linkage group 2 of the C sunki map. The phenotypic variation explained by individual QTLs was 14% for C sunki and ranged from 16 to 24% for P. trifoliala. The low character heritability (h(2) = 18.7%) and the detection of more than one QTL associated with citrus Phytophthora gummosis resistance showed that inheritance of the resistance is quantitative.

The frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis

Background and Objectives. A frequent mutation in the cystathionine beta-synthase (CBS) gene (844ins68, a 68-bp insertion in the coding region of exon 8) was recently discovered. In the present study we Investigated this mutation as a candidate risk factor for venous thrombosis.Design and Methods. The prevalence of the 844ins68 CBS mutation was determined in 101 patients with objectively diagnosed deep venous thrombosis and in 101 healthy controls matched for age, sex and race. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed to determine the genotypes, Additionally, Bsrl restriction enzyme digestion of the PCR products was performed in all samples from carriers of the insertion, to test for concurrent presence of a second mutation (T833C) in the CBS gene.Results. The insertion was found in 21 out of 101 patients (20.8%; allele frequency 0.109) and in 20 out of 101 controls (19.8%; allele frequency 0.114), yielding a relative risk for venous thrombosis related to the 844ins68 CBS mutation close to 1.0. In addition, the T833C GBS mutation was detected in all alleles carrying the 844ins68 CBS insertion, confirming the co-inheritance of the two mutations.Interpretation and Conclusions. Our findings do not support the hypothesis that the 844ins68 mutation in the CBS gene is a genetic risk factor for venous thrombosis. (C)1998, Ferrata Storti Foundation.

The frequency of 844ins68 mutation in the cystathionine β-synthase gene is not increased in patients with venous thrombosis

Background and Objectives. A frequent mutation in the cystathionine β- synthase (CBS) gene (844ins68, a 68-bp insertion in the coding region of exon 8) was recently discovered. In the present study we investigated this mutation as a candidate risk factor for venous thrombosis. Design and Methods. The prevalence of the 844ins68 CBS mutation was determined in 101 patients with objectively diagnosed deep venous thrombosis and in 101 healthy controls matched for age, sex and race. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed to determine the genotypes. Additionally, Bsrl restriction enzyme digestion of the PCR products was performed in all samples from carriers of the insertion, to test for concurrent presence of a second mutation (T833C) in the CBS gene. Results. The insertion was found in 21 out of 101 patients (20.8%; allele frequency 0.109) and in 20 out of 101 controls (19.8%; allele frequency 0.114), yielding a relative risk for venous thrombosis related to the 844ins68 CBS mutation close to 1.0. In addition, the T833C CBS mutation was detected in all alleles carrying the 844ins68 CBS insertion, confirming the co- inheritance of the two mutations. Interpretation and Conclusions. Our findings do not support the hypothesis that the 844ins68 mutation in the CBS gene is a genetic risk factor for venous thrombosis.

Complete replacement of the mitochondrial genotype in a Bos indicus calf reconstructed by nuclear transfer to a bos taurus oocyte

Due to the exclusively maternal inheritance of mitochondria, mitochondrial genotypes can be coupled to a particular nuclear genotype by continuous mating of founder females and their female offspring to males of the desired nuclear genotype. However, backcrossing is a gradual procedure that, apart from being lengthy, cannot ascertain that genetic and epigenetic changes will modify the original nuclear genotype. Animal cloning by nuclear transfer using host ooplasm carrying polymorphic mitochondrial genomes allows, among other biotechnology applications, the coupling of nuclear and mitochondrial genotypes of diverse origin within a single generation. Previous attempts to use Bos taurus oocytes as hosts to transfer nuclei from unrelated species led to the development to the blastocyst stage but none supported gestation to term. Our aim in this study was to determine whether B. taurus oocytes support development of nuclei from the closely related B. indicus cattle and to examine the fate of their mitochondrial genotypes throughout development. We show that indicus:taurus reconstructed oocytes develop to the blastocyst stage and produce live offspring after transfer to surrogate cows. We also demonstrate that, in reconstructed embryos, donor cell-derived mitochondria undergo a stringent genetic drift during early development leading, in most cases, to a reduction or complete elimination of B. indicus mtDNA. These results demonstrate that cross-subspecies animal cloning is a viable approach both for matching diverse nuclear and cytoplasmic genes to create novel breeds of cattle and for rescuing closely related endangered cattle.

Frequencies of-308G/A (TNFA) and-509C/T (TGFB1) polymorphisms in sickle cell anemia patients from Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Coeffcients of herdability and relatedness in a forest fragment of Araucaria angustifolia (Bertol.) Kuntze using genetic markers

Methods based on genetic markers to estimate the coefficient of heritability in natural populations are important to understand the effects of natural selection on inheritance of quantitative traits. The objective of this study was to investigate the genetic control of the trait plant height in a fragmented population of Araucaria angustifolia. This study was conducted in a forest fragment of 5.4 ha of area, located in the State of Parana, Brazil. Estimates of heritability were performed using data from genotypes and height of regenerating individuals of the population. Four methods to estimate the relatedness between pairs of individuals (RITLAND, 1996; LYNCH; RITLAND, 1999; QUELLER; GOODNIGHT, 1989; WANG, 2002) for three distances (without criteria, 25 and 50 m) were used. The coefficient of heritability estimated using the estimator of relatedness of Ritland (1996), suggest that the genetic control of the trait height is low in the regeneration, thus the natural selection as well as the artificial selection have a low potential to change the mean of the population. The estimates based on the other methods to calculate the relatedness presented low precision, indication that these methods are not adequate for the data used.