Dissecting Genetic Networks Underlying Complex Phenotypes: The Theoretical Framework

Great progress has been made in genetic dissection of quantitative trait variation during the past two decades, but many studies still reveal only a small fraction of quantitative trait loci (QTLs), and epistasis remains elusive. We integrate contemporary knowledge of signal transduction pathways with principles of quantitative and population genetics to characterize genetic networks underlying complex traits, using a model founded upon one-way functional dependency of downstream genes on upstream regulators (the principle of hierarchy) and mutual functional dependency among related genes (functional genetic units, FGU). Both simulated and real data suggest that complementary epistasis contributes greatly to quantitative trait variation, and obscures the phenotypic effects of many ‘downstream’ loci in pathways. The mathematical relationships between the main effects and epistatic effects of genes acting at different levels of signaling pathways were established using the quantitative and population genetic parameters. Both loss of function and “co-adapted” gene complexes formed by multiple alleles with differentiated functions (effects) are predicted to be frequent types of allelic diversity at loci that contribute to the genetic variation of complex traits in populations. Downstream FGUs appear to be more vulnerable to loss of function than their upstream regulators, but this vulnerability is apparently compensated by different FGUs of similar functions. Other predictions from the model may account for puzzling results regarding responses to selection, genotype by environment interaction, and the genetic basis of heterosis

The Shelf-Life of Sodium Hypochlorite Irrigating Solutions

Background: Sodium hypochlorite (bleach) solutions are widely used as irrigants in endodontics. Their tendency to deteriorate is worsened by environmental influences which could cause loss of available chlorine content

Pulp-test responses in orthodontic patients

The diagnosis of orofacial pain is complicated in the orthodontic patient as treatment-induced alterations to pulpal physiology may result in altered responses to pulp-test stimuli. Thirty-three subjects commencing fixed orthodontic treatment and another 15 subjects not undergoing orthodontic treatment were used in this study. Cold and electrical stimuli were applied to the maxillary incisor teeth prior to treatment, after the placement of fixed appliances and at regular intervals for both groups for up to 252 days. At baseline, response thresholds to electric testing were typically higher for orthodontic subjects, particularly for the lateral incisors. For the non-orthodontic group, the response threshold over the 252 days was relatively constant. For the orthodontic group, application of force immediately increased the response threshold to electric pulp testing, which peaked after two months. By day 252, response means for lateral incisors still remained elevated. Responses to thermal testing were more consistent and reliable. The results of this study indicate that dental practitioners should interpret responses to electric pulp testing cautiously in orthodontic patients and that thermal testing with carbon dioxide snow may be more reliable

Pulp-test responses in orthodontic patients

The diagnosis of orofacial pain is complicated in the orthodontic patient as treatment-induced alterations to pulpal physiology may result in altered responses to pulp-test stimuli. Thirty-three subjects commencing fixed orthodontic treatment and another 15 subjects not undergoing orthodontic treatment were used in this study. Cold and electrical stimuli were applied to the maxillary incisor teeth prior to treatment, after the placement of fixed appliances and at regular intervals for both groups for up to 252 days. At baseline, response thresholds to electric testing were typically higher for orthodontic subjects, particularly for the lateral incisors. For the non-orthodontic group, the response threshold over the 252 days was relatively constant. For the orthodontic group, application of force immediately increased the response threshold to electric pulp testing, which peaked after two months. By day 252, response means for lateral incisors still remained elevated. Responses to thermal testing were more consistent and reliable. The results of this study indicate that dental practitioners should interpret responses to electric pulp testing cautiously in orthodontic patients and that thermal testing with carbon dioxide snow may be more reliable

Computer simulation of a selection strategy to accommodate genotype-environment interactions in a wheat recurrent selection programme

Multi-environment trials (METs) are used in plant breeding programmes to evaluate genotypes (lines/families) as a basis for selection on expected performance (yield and/or quality) in a target population of environments (TPE). When a large component of the genotype-environment (G x E) interactions results from crossover interactions, samples of environments in METs that deviate From the TPE provide a suboptimal basis for selection of genotypes on performance expected in the TPE. To adjust for the negative effects of these deviations, a selection strategy that weights the data from the MET according to their expected frequency of occurrence in the TPE (i.e. a weighted selection strategy)was investigated. Computer simulation methodology was used to obtain preliminary information on the weighted selection strategy and compare it to the traditional unweighted selection strategy For a range of MET scenarios and G x E interaction models. The evaluation of the weighted selection strategy was conducted in context with the germplasm enhancement programme (GEP) of the Northern Wheat Improvement Programme in Australia. The results indicated that when the environments sampled in the MET matched those expected in the TPE, the unweighted and weighted selection strategies achieved a similar response to selection in the TPE. However. when the environments sampled in the MET did not match the expectations in the TPE and a large component of the G x E interactions resulted from crossover interactions, the weighted selection strategy achieved a greater response to selection in the TPE. The advantage of the weighted strategy increased as the amount of crossover G x E interaction increased or fewer environments were sampled in the METs

Power of the joint segregation analysis method for testing mixed major-gene and polygene inheritance models of quantitative traits

Understanding the genetic architecture of quantitative traits can greatly assist the design of strategies for their manipulation in plant-breeding programs. For a number of traits, genetic variation can be the result of segregation of a few major genes and many polygenes (minor genes). The joint segregation analysis (JSA) is a maximum-likelihood approach for fitting segregation models through the simultaneous use of phenotypic information from multiple generations. Our objective in this paper was to use computer simulation to quantify the power of the JSA method for testing the mixed-inheritance model for quantitative traits when it was applied to the six basic generations: both parents (P-1 and P-2), F-1, F-2, and both backcross generations (B-1 and B-2) derived from crossing the F-1 to each parent. A total of 1968 genetic model-experiment scenarios were considered in the simulation study to quantify the power of the method. Factors that interacted to influence the power of the JSA method to correctly detect genetic models were: (1) whether there were one or two major genes in combination with polygenes, (2) the heritability of the major genes and polygenes, (3) the level of dispersion of the major genes and polygenes between the two parents, and (4) the number of individuals examined in each generation (population size). The greatest levels of power were observed for the genetic models defined with simple inheritance; e.g., the power was greater than 90% for the one major gene model, regardless of the population size and major-gene heritability. Lower levels of power were observed for the genetic models with complex inheritance (major genes and polygenes), low heritability, small population sizes and a large dispersion of favourable genes among the two parents; e.g., the power was less than 5% for the two major-gene model with a heritability value of 0.3 and population sizes of 100 individuals. The JSA methodology was then applied to a previously studied sorghum data-set to investigate the genetic control of the putative drought resistance-trait osmotic adjustment in three crosses. The previous study concluded that there were two major genes segregating for osmotic adjustment in the three crosses. Application of the JSA method resulted in a change in the proposed genetic model. The presence of the two major genes was confirmed with the addition of an unspecified number of polygenes

A survey of sodium hypochlorite use by general dental practitioners and endodontists in Australia

Background: Sodium hypochlorite is used commonly as an endodontic irrigant, but there are no published reports that provide details of its use. This survey sought to determine the percentage of Australian dentists who practiced endodontics, whether they used sodium hypochlorite for irrigation, and the manner of dilution, storage and dispensing sodium hypochlorite used by both dentists and endodontists. Methods: All Australian endodontists and a stratified random sample of 200 general dentists in Australia were surveyed to address the issues identified above. Results: Almost 98 per cent of dentists surveyed performed endodontic treatment. Among endodontists, nearly 94 per cent used sodium hypochlorite for irrigation compared with just under 75 per cent of general dentists: Sodium hypochlorite use by general dentists was more common in Victoria and South Australia than in other States. An infant sanitizer (Milton or Johnson's Antibacterial Solution) was used by just over 92 per cent of general practitioners and by more than 67 per cent of endodontists. All other respondents used domestic bleach. One hundred and sixty four of the respondents (80 per cent of endodontists and over 90 per cent of general dentists) used a 1 per cent w/v solution. Ten practitioners used a 4 per cent w/v solution, five used a 2 per cent w/v solution and four used a 1.5 per cent w/v solution. Eighty per cent of the practitioners who diluted their sodium hypochlorite before use, used demineralized water for this purpose. The remainder used tap water. Only four practitioners stored sodium hypochlorite in a manner which risked light exposure and loss of available chlorine content. Conclusions: Sodium hypochlorite is commonly used as an endodontic irrigant and Australian dentists generally stored the material correctly

Strength decay of orthodontic elastomeric ligatures

Aim: To evaluate, over a 12-week period, the tensile strength (TS) and extension to TS of elastomeric ligatures (both clear and coloured) obtained from two companies. Setting Ex vivo study. Method: Seven replicates of five ligatures from two orthodontic companies were tested using an ex vivo assembly which simulated a clinical situation. Results: The ligatures tested had a similar TS decay pattern, with the TS gradually decreasing over the duration of the study. The Unitek ligatures exhibited a greater TS than their respective Ormco ligatures. Generally, all of the ligatures tested experienced an increase in the extension to TS over time. The pre-stretching procedure used in this study did not produce any long-term detrimental effects on the TS and extension to TS of the ligatures tested. Conclusions: The results of this study confirm there are differences in TS, and extension to TS between clear and coloured elastomeric ligatures, and that some significant differences also exist between different brands of elastomeric ligatures