Impacts of seed and pollen flow on population genetic structure for plant genomes with three contrasting modes of inheritance. (65/16923)

The classical island and one-dimensional stepping-stone models of population genetic structure developed for animal populations are extended to hermaphrodite plant populations to study the behavior of biparentally inherited nuclear genes and organelle genes with paternal and maternal inheritance. By substituting appropriate values for effective population sizes and migration rates of the genes concerned into the classical models, expressions for genetic differentiation and correlation in gene frequency between populations can be derived. For both models, differentiation for maternally inherited genes at migration-drift equilibrium is greater than that for paternally inherited genes, which in turn is greater than that for biparentally inherited nuclear genes. In the stepping-stone model, the change of genetic correlation with distance is influenced by the mode of inheritance of the gene and the relative values of long- and short-distance migration by seed and pollen. In situations where it is possible to measure simultaneously Fst for genes with all three types of inheritance, estimates of the relative rates of pollen to seed flow can be made for both the short- and long-distance components of migration in the stepping-stone model.  (+info)

"Quasi-REML" correlation estimates between production and health traits in the presence of selection and confounding: a simulation study. (66/16923)

Performance of the "quasi-REML" method for estimating correlations between a continuous trait and a categorical trait, and between two categorical traits, was studied with Monte Carlo simulations. Three continuous, correlated traits were simulated for identical populations and three scenarios with either no selection, selection for one moderately heritable trait (Trait 1, h2 = .25), and selection for the same trait plus confounding between sires and management groups. The "true" environmental correlations between Traits 2 (h2 = .10) and 3 (h2 = .05) were always of the same absolute size (.20), but further data scenarios were generated by setting the sign of environmental correlation to either positive or negative. Observations for Traits 2 and 3 were then reassigned to binomial categories to simulate health or reproductive traits with incidences of 15 and 5%, respectively. Genetic correlations (r(g12), r(g13), and r(g23) and environmental correlations (r(e12), r(e13), and r(e23)) were estimated for the underlying continuous scale (REML) and the visible categorical scales ("quasi-REML") with linear multiple-trait sire and animal models. Contrary to theory, practically all "quasi-REML" genetic correlations were underestimated to some extent with the sire and animal models. Selection inflated this negative bias for sire model estimates, and the sign of r(e23) noticeably affected r(g23) estimates for the animal model, with greater bias and SD for estimates when the "true" r(e23) was positive. Transformed "quasi-REML" environmental correlations between a continuous and a categorical trait were estimated with good efficiency and little bias, and corresponding correlations between two categorical traits were systematically overestimated. Confounding between sires and contemporary groups negatively affected all correlation estimates on the underlying and the visible scales, especially for sire model "quasi-REML" estimates of genetic correlation. Selection, data structure, and the (co)variance structure influences how well correlations involving categorical traits are estimated with "quasi-REML" methods.  (+info)

Properties of threshold model predictions. (67/16923)

Estimation of genetic parameters and accuracy of threshold model genetic predictions were investigated. Data were simulated for different population structures by using Monte Carlo techniques. Variance components were estimated by using threshold models and linear sire models applied to untransformed data, logarithmically transformed data, and transformation to Snell scores. Effects of number of categories (2, 5, and 10), incidence of categories (extreme, moderate, and normal), heritability in the underlying scale (.04, .20, and .50), and data structure (unbalanced and balanced) on accuracy of genetic prediction were investigated. The real importance of using a threshold model was to estimate genetic parameters. An expected heritability of .20 was estimated to be .22 and .10 by a threshold model and a linear model, respectively. Accuracy increased significantly with a larger number of categories, a more normal distribution of incidences, increased heritability, and more balanced data. Even threshold models were shown to be more efficient with more than two categories (e.g., binomial). Transformation of scale did not accomplish the purpose intended.  (+info)

Analysis of time-to-pregnancy data. (68/16923)

Statistical models for time-to-pregnancy data are usually formulated in discrete time. Two approaches were surveyed, including methods of accounting for both known heterogeneity (covariates, possibly time-dependent) and unknown heterogeneity (frailty). Delicate censoring and truncation patterns arose for prospective and, particularly, retrospective sampling designs. The inclusion of several pregnancies per couple presents new challenges and possibilities.  (+info)

Measuring reproducibility of regional brain metabolic responses to lorazepam using statistical parametric maps. (69/16923)

Statistical parametric mapping (SPM) is a method for localizing differences in brain activation patterns without the need for anatomic predefined constraints. The purpose of this study was to assess the reproducibility of the patterns of activation obtained with SPM for baseline measures and for metabolic changes in response to lorazepam on a test-retest design. The results were compared with those we previously published using region-of-interest (ROI) methods. METHODS: Sixteen healthy right-handed men were scanned twice with PET and [18F]fluorodeoxyglucose (FDG): before placebo and before lorazepam (30 microg/kg). The same double FDG procedure was repeated 6-8 wk later to assess test-retest reproducibility. Image datasets were analyzed by using SPM95 software. Difference images between baseline and lorazepam were compared for the first and second evaluations, both for relative decreases as well as increases in metabolism. Significance level was systematically varied to P < 0.001, P < 0.01 and P < 0.05. RESULTS: There were no differences in the baseline SPM maps obtained for the first and second evaluations. SPM showed similar, although not identical, differences in response to lorazepam between the two evaluations. Both evaluations showed significant decreases in occipital cortex (9.7% and 10%) and significant relative increases in left temporal pole (6.8% and 10.4%). However, the second evaluation showed a decrease in the left frontal cortex (areas 6 and 8), which was not present in the first evaluation. The results were very similar to those we had obtained with ROI methods, except for the activation in the left temporal pole, which we had not observed with ROI analyses. CONCLUSION: Although the overall pattern of lorazepam-induced activation depicted by SPM was reproducible in pattern and magnitude, there were some differences that included a left frontal area of deactivation during the second but not the first evaluation. Results with SPM are similar to those with the ROI method, and, because it systematically analyses the whole brain, SPM can uncover patterns not seen with the ROI method.  (+info)

Simulations of the T <--> R conformational transition in aspartate transcarbamylase. (70/16923)

Aspartate transcarbamylase (ATCase) from Escherichia coli is one of the best known allosteric enzymes. In spite of numerous experiments performed by biochemists, no consensus model for the cooperative transition between the tensed (T) and the relaxed (R) forms exists. It is hypothesized, however, that changes in the quaternary structure play a key role in the allosteric properties of oligomeric proteins such as ATCase. Previous normal mode calculations of the two states of ATCase illustrated the type of motions that could be important in initiating the transition. In this work four pathways for the transition were calculated using the targeted molecular dynamics (TMD) method without constraint on the symmetry of the system. The most important quaternary structure changes are the relative rotation and translation of the catalytic trimers and the rotations of the regulatory dimers. The simulations show that these quaternary changes start immediately and finish when about 70% of the transition is completed whereas there are tertiary changes throughout the transition. In agreement with the work of Lipscomb et al., it was found that the relative translation between the catalytic trimers appears to play a central role in allowing the transition to occur. In all the simulations differences are observed in the opening and closing behaviours of the domains in the catalytic and regulatory chains that could provide a structural interpretation for the results of certain site-directed mutagenesis experiments. Overall the motions of the subunits are concerted even though the constraint imposed on the TMD method does not explicitly require that this be so.  (+info)

An appraisal of the Peer Assessment Rating (PAR) Index and a suggested new weighting system. (71/16923)

The PAR Index was developed to measure treatment outcome in orthodontics. Validity was improved by weighting the scores of some components to reflect their relative importance. However, the index still has limitations, principally due to the high weight assigned to overjet. Difficulties also arise from the application of one weighting system to all malocclusions, since occlusal features vary in importance in different classes of malocclusion. The present study examined PAR Index validity using orthodontic consultant assessments as the 'Gold standard' and clinical ranking of occlusal features and statistical modelling to derive a new weighting system, separate for each malocclusion class. Discriminant and regression analyses were used to derive new criteria for measuring treatment outcome. As a result a new and more sensitive method of assessment is suggested which utilizes a combination of point and percentage reductions in PAR scores. This was found to have better correlations with the 'Gold standard' than the PAR nomogram.  (+info)

Performance of a predictive model to identify undiagnosed diabetes in a health care setting. (72/16923)

OBJECTIVE: To develop a predictive model to identify individuals with an increased risk for undiagnosed diabetes, allowing for the availability of information within the health care system. RESEARCH DESIGN AND METHODS: A sample of participants from the Rotterdam Study (n = 1,016), aged 55-75 years, not known to have diabetes completed a questionnaire on diabetes-related symptoms and risk factors and underwent a glucose tolerance test. Predictive models were developed using stepwise logistic regression analyses with the absence or presence of newly diagnosed diabetes as the dependent variable and various items with a plausible connection to diabetes as the independent variables. The models were evaluated in another Dutch population-based study, the Hoorn Study (n = 2,364), in which the participants were aged 50-74 years. Performances of the predictive models were compared by using receiver-operator characteristics (ROC) curves. RESULTS: We developed three predictive models (PMs), PM1 contained information routinely collected by the general practitioner, while PM2 also contained variables obtainable by additional questions. The third predictive model, PM3, included variables that had to be obtained from a physical examination. These latter variables did not have additive predictive value, resulting in a PM3 similar to PM2. The area under the ROC curve was higher for PM2 than for PM1, but the 95% Cls overlapped (0.74 [0.70-0.78] and 0.68 [0.64-0.72], respectively). CONCLUSIONS: Using only information normally present in the files of a general practitioner, a predictive model was developed that performed similarly to one supplemented by information obtained from additional questions. The simplicity of PM1 makes it easy to implement in the current health care setting.  (+info)