Linkage analysis versus association analysis: distinguishing between two models that explain disease-marker associations.

Human genetics researchers have been intrigued for many years by weak-to-moderate associations between markers and diseases. However, in most cases of association, the cause of this phenomenon is still not known. Recently, interest has grown in pursuing association studies for complex diseases, either instead of or in addition to linkage studies. Hence, it is timely to reconsider what a disease-marker association, particularly in the weak-to-moderate range (relative risk < 10), can tell us about disease etiology. To this end, this study accomplishes three aims: (1) It formulates two different models explaining weak-to-moderate associations and derives the relationship between them. One is a linkage disequilibrium model, and the other is a "susceptibility," or pure association, model. The importance of drawing the distinction between these two models and the implications for our understanding of the genetics of human disease will also be discussed. It will be argued that the linkage disequilibrium model represents true linkage but that the susceptibility model does not. (2) It examines two family-based association tests proposed recently by Parsian et al. and Spielman et al. and derives formulas for their behavior under the two models described above. It demonstrates that these tests yield almost identical results under these two models. It shows that, whereas these tests can confirm an association, they cannot determine whether the association is caused by the linkage disequilibrium model or the susceptibility model. The study also characterizes the probabilities yielded by the family association tests in the presence of weak-to-moderate associations, which will aid researchers using these tests. (3) It proposes two approaches, both based on linkage analysis, which can distinguish between the two models described above. One approach involves a straightforward linkage analysis of the data; the other involves a partitioned association-linkage (PAL) test, as suggested by Greenberg. Formulas are derived for testing identity by descent in affected sib pairs by using both approaches. (4) Finally, the formulas and arguments are illustrated with two examples from the literature and one computer-simulated data set.     

CHLOROPLAST DNA EVIDENCE FOR THE INTERRELATIONSHIPS OF TOMATOES,POTATOES, AND PEPINOS (SOLANACEAE)

We used chloroplast DNA restriction site analysis to test hypotheses of relationships of Solarium subgenus Potatoe (including potatoes and pepinos), two other Solanum, Cyphomandra (the tree tomatoes), and Lycopersicon (the tomatoes). Capsicum and Datura were used as outgroups. The results support two main clades among the taxa we studied: 1) Solanum subgenus Potatoe and Lycopersicon; and 2) other Solanum and Cyphomandra. Within the first clade, the following groups were supported: a) sect. Basarthrum and sect. Anarrhichomenum; b) sect. Etuberosum; c) sect. Petota; d) sect. Juglandifolium, including subsect. Lycopersicoides; and e) the genus Lycopersicon. These results, in combination with an analysis of morphological data, advocate the controversial, but previously suggested, treatment of Lycopersicon as congeneric with Solanum in subgenus Potatoe. Thus, the cultivated tomato will be recognized as Solanum lycopersicum L. Solanum chmielewskii and Solanum lycopersicum var. cerasiforme are proposed as new combinations; Solanum neorickii is proposed as a new name for Lycopersicon parviflorum. Our data also suggest that Cyphomandra should be included within Solanum.     

Hand preference in capuchin monkeys varies with age

The purpose of this research was to examine the influence of age on hand preference in capuchin monkeys (Cebus apella). Twenty-two capuchins, aged 6 months to 30 years, were presented with a task that involved reaching for food and a task that involved using sponging tools to absorb juice. Adults exhibited a greater percentage of right-handed actions in each task than did immature subjects. Adults also exhibited a stronger lateral bias than did immature subjects in the sponging task. These results are consistent with hypotheses: a) adult capuchin monkeys are biased toward use of their right hand for reaching; b) adult capuchins exhibit a greater incidence of right-hand preference than do immature capuchins; and c) primates exhibit age-related differences in the strength and direction of hand preference in tasks that involve the use of tools.     

Energetics and regulations of formate and hydrogen metabolism by Methanobacterium formicicum

Accumulation of formate to millimolar levels was observed during the growth of Methanobacterium formicicum species on H₂–CO₂. Hydrogen was also produced during formate metabolism by M. formicicum. The amount of formate accumulated in the medium or the amount H₂ released in gas phase was influenced by the bicarbonate concentration. The formate hydrogenlyase system was constitutive but regulated by formate. When methanogenesis was inhibited by addition of 2-bromoethane sulfonate, M. formicicum synthesized formate from H₂ plus HCO _inf3 ^sup- or produced H₂ from formate to a steady-state level at which point the Gibbs free energy (G) available for formate synthesis or H₂ production was approximately -2 to -3 kJ/reaction. Formate conversion to methane was inhibited in the presence of high H₂ pressure. The relative rates of conversion of formate and H₂ were apparently controlled by the G available for formate synthesis, hydrogen production, methane production from formate and methane production from H₂. Results from ¹⁴C-tracer tests indicated that a rapid isotopic exchange between HCOO^- and HCO _inf3 ^sup- occurred during the growth of M. formicicum on H₂–CO₂. Data from metabolism of ¹⁴C-labelled formate to methane suggested that formate was initially split to H₂ and HCO _inf3 ^sup- and then subsequently converted to methane. When molybdate was replaced with tungstate in the growth media, the growth of M. formicicum strain MF on H₂–CO₂ was inhibited although production of methane was not Formate synthesis from H₂ was also inhibited.     

The effect of temperature,light-spectrum,desiccation and salinity gradients on the photosynthetic performance of a subtidal brown alga,Sargassum macrocarpum,from Japan

The effect of temperature, light-spectrum, desiccation and salinity gradients on the photosynthesis of a Japanese subtidal brown alga, Sargassum macrocarpum (Fucales), was determined using a pulse amplitude modulation-chlorophyll fluorometer and dissolved oxygen sensors. Temperature responses of the maximum (F_v/F_m in darkness) and effective (ΔF/F_m′ at 50 μmol photons m⁻² s⁻¹; = Φ_PSII) quantum yields during 6-day culture (4–36°C) remained high at 12–28°C, but decreased at higher temperatures. Nevertheless, ΔF/F_m′ also dropped at temperatures below 8°C, suggesting light sensitivity under chilling temperatures because F_v/F_m remained high. Photosynthesis–irradiance responses at 24°C under red (660 nm), green (525 nm), blue (450 nm) and white light (metal halide lamp) showed that maximum net photosynthesis under blue and white light was greater than under red and green light, indicating the sensitivity and photosynthetic availability of blue light in the subtidal light environment. In the desiccation experiment, samples under aerial exposure of up to 8 h under dim-light at 24°C and 50% humidity showed that ΔF/F_m′ quickly declined after more than 45 min of emersion; furthermore, ΔF/F_m′ also failed to recover to initial levels even after 1 day of rehydration in seawater. Under the emersion state, the ΔF/F_m′ remained high when the relative water content (RWC) was greater than 50%; in contrast, it quickly dropped when the RWC was less than 50%. When the RWC was reduced below 50%, ΔF/F_m′ did not return to initial levels, regardless of subsequent re-hydration, suggesting a low capacity of photosynthesis to recover from desiccation. The stenohaline response of photosynthesis under 3-day culture is evident, given that ΔF/F_m′ declined when salinity was beyond 20–40 psu. Adaptation to subtidal environments in temperate waters of Japan can be linked to these traits.     

Non-linear loss of suitable wine regions over Europe in response to increasing global warming

Evaluating the potential climatic suitability for premium wine production is crucial for adaptation planning in Europe. While new wine regions may emerge out of the traditional boundaries, most of the present-day renowned winemaking regions may be threatened by climate change. Here, we analyse the future evolution of the geography of wine production over Europe, through the definition of a novel climatic suitability indicator, which is calculated over the projected grapevine phenological phases to account for their possible contractions under global warming. Our approach consists in coupling six different de-biased downscaled climate projections under two different scenarios of global warming with four phenological models for different grapevine varieties. The resulting suitability indicator is based on fuzzy logic and is calculated over three main components measuring (i) the timing of the fruit physiological maturity, (ii) the risk of water stress and (iii) the risk of pests and diseases. The results demonstrate that the level of global warming largely determines the distribution of future wine regions. For a global temperature increase limited to 2°C above the pre-industrial level, the suitable areas over the traditional regions are reduced by about 4%/°C rise, while for higher levels of global warming, the rate of this loss increases up to 17%/°C. This is compensated by a gradual emergence of new wine regions out of the traditional boundaries. Moreover, we show that reallocating better-suited grapevine varieties to warmer conditions may be a viable adaptation measure to cope with the projected suitability loss over the traditional regions. However, the effectiveness of this strategy appears to decrease as the level of global warming increases. Overall, these findings suggest the existence of a safe limit below 2°C of global warming for the European winemaking sector, while adaptation might become far more challenging beyond this threshold.     

Fluorescence Microscopy of Fresh Tissue as a Rapid Technique for Assessing Early Injury to Mesophyll

A technique was developed for sectioning fresh red spruce foliage (Picea rubens Sarg.) for use in fluorescence microscopy. This allowed rapid examination of mesophyll in 3-5 mm needle sections. Healthy, ozone treated and cold stressed needles were examined to assess the utility of this technique for early detection of damage. Healthy mesophyll cells fluoresced bright red, while injured cells fluoresced yellow-green in ozone treated needles, and yellow-orange in frozen needles. Shifts in fluorescence wavelengths may be useful for early detection of injury to mesophyll before it is evident by standard light or electron microscopy.     

Henipaviruses and lyssaviruses target nucleolar treacle protein and regulate ribosomal RNA synthesis

The nucleolus is a common target of viruses and viral proteins, but for many viruses the functional outcomes and significance of this targeting remains unresolved. Recently, the first intranucleolar function of a protein of a cytoplasmically-replicating negative-sense RNA virus (NSV) was identified, with the finding that the matrix (M) protein of Hendra virus (HeV) (genus Henipavirus, family Paramyxoviridae) interacts with Treacle protein within nucleolar subcompartments and mimics a cellular mechanism of the nucleolar DNA-damage response (DDR) to suppress ribosomal RNA (rRNA) synthesis. Whether other viruses utilise this mechanism has not been examined. We report that sub-nucleolar Treacle targeting and modulation is conserved between M proteins of multiple Henipaviruses, including Nipah virus and other potentially zoonotic viruses. Furthermore, this function is also evident for P3 protein of rabies virus, the prototype virus of a different RNA virus family (Rhabdoviridae), with Treacle depletion in cells also found to impact virus production. These data indicate that unrelated proteins of viruses from different families have independently developed nucleolar/Treacle targeting function, but that modulation of Treacle has distinct effects on infection. Thus, subversion of Treacle may be an important process in infection by diverse NSVs, and so could provide novel targets for antiviral approaches with broad specificity.     

Isolation of signaling mutants of tomato (Lycopersicon esculentum)

As a first step towards developing a genetic system for investigating signaling processes in plants, we have developed a screen for signaling mutants deficient in a wound response. We have isolated two mutants of tomato that lack detectable production of proteinase inhibitors induced systemically in leaves by wounding. The mutants are deficient in the induction of both proteinase Inhibitor I and proteinase Inhibitor II but can be induced to respond at near wild-type levels by methyl jasmonate, a known elicitor of inhibitor production in tomato. While completely deficient in systemic production of proteinase inhibitors, both mutants produce some proteinase inhibitor in wounded leaves. This evidence suggests the existence of two signaling pathways, one local and one systemic, that regulate the induction of proteinase inhibitor snythesis in response to wounding.