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Hosts
Kinds of Hosts Selected AbstractsMUSEUM SPECIMENS AND PHYLOGENIES ELUCIDATE ECOLOGY'S ROLE IN COEVOLUTIONARY ASSOCIATIONS BETWEEN MITES AND THEIR BEE HOSTSEVOLUTION, Issue 6 2007Pavel B. Klimov Coevolutionary associations between hosts and symbionts (or parasites) are often reflected in correlated patterns of divergence as a consequence of limitations on dispersal and establishment on new hosts. Here we show that a phylogenetic correlation is observed between chaetodactylid mites and their hosts, the long-tongued bees; however, this association manifests itself in an atypical fashion. Recently derived mites tend to be associated with basal bee lineages, and vice versa, ruling out a process of cospeciation, and the existence of mites on multiple hosts also suggests ample opportunity for host shifts. An extensive survey of museum collections reveals a pattern of infrequent host shifts at a higher taxonomic level, and yet, frequent shifts at a lower level, which suggests that ecological constraints structure the coevolutionary history of the mites and bees. Certain bee traits, particularly aspects of their nesting behavior, provide a highly predictive framework for the observed pattern of host use, with 82.1% of taxa correctly classified. Thus, the museum survey and phylogenetic analyses provide a unique window into the central role ecology plays in this coevolutionary association. This role is apparent from two different perspectives,as (a) a constraining force evident in the historical processes underlying the significant correlation between the mite and bee phylogenies, as well as (b) by the highly nonrandom composition of bee taxa that serve as hosts to chaetodactylid mites. [source] HAPLODIPLOIDY AS AN OUTCOME OF COEVOLUTION BETWEEN MALE-KILLING CYTOPLASMIC ELEMENTS AND THEIR HOSTSEVOLUTION, Issue 4 2004Benjamin B. Normark Abstract Haplodiploidy (encompassing both arrhenotoky and paternal genome elimination) could have originated from coevolution between male-killing endosymbiotic bacteria and their hosts. In insects, haplodiploidy tends to arise in lineages that rely on maternally transmitted bacteria for nutrition and that have gregarious broods in which competition between siblings may occur. When siblings compete, there is strong selection on maternally transmitted elements to kill males. I consider a hypothetical bacterial phenotype that renders male zygotes effectively haploid by preventing chromosome decondensation in male-determining sperm nuclei. By causing high male mortality, such a phenotype can be advantageous to the bacterial lineage. By eliminating paternal genes, it can also be advantageous to the host female. A simple model shows that the host female will benefit under a wide range of values for the efficiency of resource re-allocation, the efficiency of transmission, and the viability of haploid males. This hypothesis helps to explain the ecological correlates of the origins of haplodiploidy, as well as such otherwise puzzling phenomena as obligate cannibalism by male Micromalthus beetles, reversion to diploidy by aposymbiotic male stictococcid scale insects, and the bizarre genomic constitution of scale insect bacteriomes. [source] Analysis of the Voltammetric Response of Electroactive Guests in the Presence of Non-Electroactive Hosts at Moderate ConcentrationsELECTROANALYSIS, Issue 18 2004Sandra Mendoza Abstract In this work, we present a method to analyze the voltammetric response of reversible redox systems involving molecules that, bearing m non-interactive electroactive sites, can undergo fast complexation equilibria with host molecules present at concentrations of the same order of magnitude as those of the electroactive guest. The approach focuses on systems for which the relative values of the binding constants for the oxidized and reduced forms of the guest result in the displacement of the voltammetric response of the electroactive molecule as the concentration of the host is increased in the electrolytic solution. This behavior is commonly known as "one wave shift behavior". Based on a series of assumptions, the method allows calculation of all the thermodynamic parameters that describe the electrochemical and complexation equilibria of a given host-guest system. The main strength of the suggested method, however, relies on the fact that it only requires cyclic voltammetry data and that it can be used for systems in which large concentrations of the host can not be employed either due to important changes of the ionic strength or to solubility problems. Although the accuracy of the obtained information is limited by the quality of the data provided by the technique, and by the assumptions employed, it certainly represents an excellent starting point for subsequent refinement either using digital simulations or an independent experimental technique. [source] Hosts and symptoms of Plum pox virus: fruiting Prunus speciesEPPO BULLETIN, Issue 2 2006G. Llácer A description of plum pox (sharka) symptoms on European and Japanese plum, apricot, peach, sweet and sour cherry and almond is presented. Plum pox is a serious disease mainly because it produces severe symptoms on fruits of numerous cultivars of Prunus species, causing fruit to fall or making them unfit for consumption. [source] Hosts of Verticillium dahliae in Kriti (Greece),EPPO BULLETIN, Issue 2 2000E. K. Ligoxigakis Naturally wilted cultivated and weed species were collected from several fields in Kriti (GR) over the years 1992/1997, and tested by isolation for the presence of Verticillium dahliae. The fungus was most frequently recovered from cultivated Solanaceae and Cucurbitaceae. Infection of many known Verticillium hosts was confirmed, and the fungus was found for the first time in Kriti in pistachio and grapevine and in several common weeds. [source] Drastic Solid-State Fluorescence Enhancement Behaviour of Phenanthro[9,10- d]imidazole-Type Fluorescent Hosts upon Inclusion of Carboxylic AcidsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 34 2009Yousuke Ooyama Abstract The crystals of phenanthro[9,10- d]imidazole-type fluorescent host 1 exhibit drastic fluorescence enhancement behaviour with a redshift in the emission maximum upon enclathration of various carboxylic acids such as formic acid, acetic acid and propionic acid. The optical changes are greatly dependent on the identity of the enclathrated carboxylic acids. The fluorescent clathrate compounds are formed not only by cocrystallization from carboxylic acid solutions but also by solid (fluorescent host),gas (carboxylic acid vapour) contact. Furthermore, when the acetic acid inclusion crystals are exposed to propionic acid vapour, acetic acid is gradually replaced by propionic acid. The guest exchange of the inclusion crystals was accompanied with colour and fluorescent intensity changes. The X-ray structural analyses of the guest-free and carboxylic acid inclusion compounds demonstrated that the destructions of the ,,, interactions, and the intermolecular hydrogen bonds binding fluorophores were induced by the enclathrated carboxylic acid molecules. Moreover, the imidazole ring of the host is protonated by the enclathrated carboxylic acid proton. On the basis of the spectroscopic data and the crystal structures, the effects of the enclathrated carboxylic acid on the solid-state photophysical properties of the clathrate compounds are discussed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Synthesis of Dicarboxylate "C-Clamp" 1,2-Diethynylarene Compounds as Potential Transition-Metal Ion HostsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 1 2008Erwin Reisner Abstract We report an efficient convergent synthesis of a new type of C-clamp ligand with a 1,2-diethynylarene scaffold involving a chelate host capable of binding a guest molecule in its endo -dicarboxylate pocket. The chemistry involves a combination of palladium-catalyzed Sonogashira, Heck, and Suzuki cross-coupling reactions. The compounds 2,3-bis[2-(2,-carboxybiphenyl-4-yl)ethynyl]triptycene and 4,5-bis[2-(2,-carboxybiphenyl-4-yl)ethynyl]veratrole and their 2,-carboxy- m -terphenyl-4-yl analogues were designed as dinucleating ligands to assemble carboxylate-bridged transition-metal complexes with a windmill geometry. The X-ray crystal structure of one such C-clamp compound containing co-crystallized water molecules reveals strong hydrogen bonds of the aqua guest to the endo -oriented carboxylic acid entities of the C-clamp host. In addition, two syn -N-donor ligands were prepared as a synthetic scaffold to mimic the geometric arrangement of N-donor atoms in carboxylate-bridged dinuclear proteins. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Tuning the Optoelectronic Properties of Carbazole/Oxadiazole Hybrids through Linkage Modes: Hosts for Highly Efficient Green ElectrophosphorescenceADVANCED FUNCTIONAL MATERIALS, Issue 2 2010Youtian Tao Abstract A series of bipolar transport host materials: 2,5-bis(2-(9H -carbazol-9-yl)phenyl)-1,3,4-oxadiazole (o -CzOXD) (1), 2,5-bis(4-(9H -carbazol-9-yl)phenyl)-1,3,4-oxadiazole (p -CzOXD) (2), 2,5-bis(3-(9H -carbazol-9-yl)phenyl)-1,3,4-oxadiazole (m -CzOXD) (3) and 2-(2-(9H -carbazol-9-yl)phenyl)-5-(4-(9H-carbazol-9-yl)phenyl)-1,3,4-oxadiazole (op -CzOXD) (4) are synthesized through simple aromatic nucleophilic substitution reactions. The incorporation of the oxadiazole moiety greatly improves their morphological stability, with Td and Tg in the range of 428,464,°C and 97,133,°C, respectively. The ortho and meta positions of the 2,5-diphenyl-1,3,4-oxadiazole linked hybrids (1 and 3) show less intramolecular charge transfer and a higher triplet energy compared to the para-position linked analogue (2). The four compounds exhibit similar LUMO levels (2.55,2.59,eV) to other oxadiazole derivatives, whereas the HOMO levels vary in a range from 5.55,eV to 5.69,eV, depending on the linkage modes. DFT-calculation results indicate that 1, 3, and 4 have almost complete separation of their HOMO and LUMO levels at the hole- and electron-transporting moieties, while 2 exhibits only partial separation of the HOMO and LUMO levels possibly due to intramolecular charge transfer. Phosphorescent organic light-emitting devices fabricated using 1,4 as hosts and a green emitter, Ir(ppy)3 or (ppy)2Ir(acac), as the guest exhibit good to excellent performance. Devices hosted by o -CzOXD (1) achieve maximum current efficiencies (,c) as high as 77.9,cd A,1 for Ir(ppy)3 and 64.2,cd A,1 for (ppy)2Ir(acac). The excellent device performance may be attributed to the well-matched energy levels between the host and hole-transport layers, the high triplet energy of the host and the complete spatial separation of HOMO and LUMO energy levels. [source] Hosts and distribution of Collybia fusipes in France and factors related to the disease's severityFOREST PATHOLOGY, Issue 1 2002D. PIOU Using data collected by two different observation networks, it was possible to clarify the distribution of Collybia fusipes in France. It is frequently found in the western and northern parts of France, mainly on Quercus rubra and Quercus robur, and to a somewhat lesser extent on Quercus petraea. When the relative areas covered by these species are compared, it is evident that Q. rubra is much the most susceptible of the three species. The fungus has been less frequently reported in the south-eastern quarter of France, where Quercus ilex and Quercus pubescens are the dominant species. Complementary observations carried out at the National Arboretum of Les Barres indicate that a large number of oak species are susceptible to infection by this fungus, particularly those in the subgenus Erythrobalanus. These observations are discussed with reference to reports of this fungus throughout Europe. In a Q. rubra stand, fruit-body clumps were monitored and root damage was assessed on 73 final-crop trees and 40 codominant trees. The results suggest that C. fusipes does not preferentially infect weakened trees. Both the severity of root damage and the number of fruit-body clumps increased with increasing depth to signs of waterlogging. Répartition et hôtes de Collybia fusipes en France et facteurs de gravité de la maladie D'après les données collectées par deux réseaux de surveillance distincts, la répartition de Collybia fusipes en France a été précisée. Le champignon est fréquent dans les moitiés ouest et nord du pays, principalement sur Quercus rubra et Q. robur, et dans une moindre mesure sur Q. petraea. Quand on considère la surface relative occupée par ces espèces, il apparaît évident que Q. rubra est le plus sensible. Il a été moins souvent signalé dans le quart sud-est oùQ. ilex et Q. pubescens sont dominants. Des observations complémentaires réalisées à l'Arboretum National des Barres indiquent qu'un grand nombre d'espèces de chênes sont susceptibles d'être attaquées par ce champignon, particulièrement celles du sous-genre Erythrobalanus. Ces observations sont discutées et comparées avec les données disponibles en Europe. L'apparition des carpophores a été suivie dans un peuplement de Q. rubra, et les dégâts aux racines ont étéévalués sur 73 arbres de place et 40 arbres codominants. Les résultats indiquent que C. fusipes n'infecte pas plus gravement les arbres affaiblis. Le degré d'hydromorphie influence significativement l'importance des dégâts racinaires ainsi que le nombre de carpophores produits. Cette étude confirme que C. fusipes se développe préférentiellement dans les sites où l'hydromorphie n'est pas trop sévère. Wirtspflanzen und Verbreitung von Collybia fusipes in Frankreich sowie mit der Krankheitsintensität assoziierte Umweltfaktoren Mit Hilfe der Daten von zwei unterschiedlichen Beobachtungsnetzwerken konnte die Verbreitung von Collybia fusipes in Frankreich präzisiert werden. Der Pilz ist im Westen und Norden des Landes häufig auf Quercus rubra und Quercus robur zu finden, etwas weniger häufig auf Quercus petraea. Beim Vergleich der von diesen Arten bestockten Flächen wird deutlich, dass Q. rubra die anfälligste der drei Eichenarten ist. Im südöstlichen Teil Frankreichs, wo Quercus ilex und Quercus pubescens dominieren, wurde der Pilz weniger häufig nachgewiesen. Ergänzende Beobachtungen im Arboretum National des Barres ergaben, dass zahlreiche Eichenarten gegen C. fusipes anfällig sind, insbesondere die des Subgenus Erythrobalanus. Diese Ergebnisse werden im Vergleich mit der aus Europa über diesen Pilz verfügbaren Literatur diskutiert. In einem Q. rubra, Bestand wurde das Auftreten von Fruchtkörpern und von Wurzelschäden an 73 herrschenden und 40 mitherrschenden Bäumen registriert. Die Ergebnisse zeigen, dass C. fusipes geschwächte Bäume nicht bevorzugt befällt. Sowohl die Intensität der Wurzelschäden als auch die Anzahl der Fruchtkörper erhöhte sich mit zunehmender Tiefe der Anzeichen für Staunässe im Bodenprofil. [source] Versatile, Benzimidazole/Amine-Based Ambipolar Compounds for Electroluminescent Applications: Single-Layer, Blue, Fluorescent OLEDs, Hosts for Single-Layer, Phosphorescent OLEDsADVANCED FUNCTIONAL MATERIALS, Issue 16 2009Chih-Hsin Chen Abstract A series of compounds containing arylamine and 1,2-diphenyl-1H -benz[d]imidazole moieties are developed as ambipolar, blue-emitting materials with tunable blue-emitting wavelengths, tunable ambipolar carrier-transport properties and tunable triplet energy gaps. These compounds possess several novel properties: (1) they emit in the blue region with high quantum yields; (2) they have high morphological stability and thermal stability; (3) they are capable of ambipolar carrier transport; (4) they possess tunable triplet energy gaps, suitable as hosts for yellow-orange to green phosphors. The electron and hole mobilities of these compounds lie in the range of 0.68,144,×,10,6 and 0.34,147,×,10,6,cm2 V,1 s,1, respectively. High-performance, single-layer, blue-emitting, fluorescent organic light-emitting diodes (OLEDs) are achieved with these ambipolar materials. High-performance, single-layer, phosphorescent OLEDs with yellow-orange to green emission are also been demonstrated using these ambipolar materials, which have different triplet energy gaps as the host for yellow-orange-emitting to green-emitting iridium complexes. When these ambipolar, blue-emitting materials are lightly doped with a yellow-orange-emitting iridium complex, white organic light-emitting diodes (WOLEDs) can be achieved, as well by the use of the incomplete energy transfer between the host and the dopant. [source] Modified Cyclodextrins as Enantioselective Hosts for Amino AcidsHELVETICA CHIMICA ACTA, Issue 4 2008Pavan Kumar, Vydyula Abstract Two modified , -cyclodextrins, H-2 and H-3, having a flexible appended moiety were studied for the chiral discrimination of the enantiomers of various amino acids by means of fluorescence as signaling option. These hosts quenched the fluorescence intensities of amino acids upon binding. The d- enantiomers were better recognized by these hosts. The association constants (Ks) and enantioselectivity factors (,) of the host,guest complexes were calculated. [source] Solution-Processable Carbazole-Based Conjugated Dendritic Hosts for Power-Efficient Blue-Electrophosphorescent DevicesADVANCED MATERIALS, Issue 48 2009Junqiao Ding A novel class of hosts suitable for solution processing has been developed based on a conjugated dendritic scaffold. By increasing the dendron generation, the highest occupied molecular orbital (HOMO) energy level can be tuned to facilitate hole injection, while the triplet energy remains at a high level, sufficient to host high-energy-triplet emitters. A power-efficient blue-electrophosphorescent device based on H2 (see figure) is presented. [source] Climate change and range expansion of an aggressive bark beetle: evidence of higher beetle reproduction in naïve host tree populationsJOURNAL OF APPLIED ECOLOGY, Issue 5 2010Timothy J. Cudmore Summary 1.,Hosts may evolve defences that make them less susceptible and suitable to herbivores impacting their fitness. Due to climate change-driven range expansion, herbivores are encountering naïve host populations with increasing frequency. 2.,Aggressive bark beetles are among the most important agents of disturbance in coniferous forest ecosystems. The presence of bark beetle outbreaks in areas with a historically unsuitable climate, in part a consequence of climate change, provided an opportunity to assess the hypothesis that the mountain pine beetle Dendroctonus ponderosae has higher reproductive success in lodgepole pine Pinus contorta trees growing in areas that have not previously experienced frequent outbreaks. 3.,We felled and sampled mountain pine beetle-killed trees from historically climatically suitable and unsuitable areas, i.e. areas with and without a historical probability of frequent outbreaks. Reproductive success was determined from a total of 166 trees from 14 stands. 4.,Brood productivity was significantly affected by climatic suitability class, such that mean brood production per female increased as historical climatic suitability decreased. 5.,Synthesis and applications. The current study demonstrates that the mountain pine beetle has higher reproductive success in areas where its host trees have not experienced frequent beetle epidemics, which includes much of the current outbreak area in north central British Columbia. This increased productivity of mountain pine beetle is likely to have been a key reason for the rapid population buildup that resulted in unprecedented host tree mortality over huge areas in western Canada. The outbreak thus provides an example of how climate change-driven range expansion of native forest insects can have potentially disastrous consequences. Since an increased reproductive success is likely to accelerate the progression of outbreaks, it is particularly critical to manage forests for the maintenance of a mosaic of species and age classes at the landscape level in areas where host tree populations are naïve to eruptive herbivores. [source] Optimization of RT,PCR for the Detection of Bean leaf roll virus in Plant Hosts and Insect VectorsJOURNAL OF PHYTOPATHOLOGY, Issue 2 2005V. Ortiz Abstract The detection of luteoviruses by reverse transcription polymerase chain reaction (RT,PCR) depends on the adequate quality and quantity of extracted viral nucleic acids. We have optimized the detection of Bean leaf roll virus (BLRV) using selective precipitation by LiCl of viral RNA from a small quantity of infected plant tissues and insect vectors. The optimal template for PCR was 15 ,l of RT reaction mixture. BLRV was detected in different plant hosts and aphid vectors and Aphis fabae, previously considered to be a non-vector of BLRV, was found to acquire the virus from infected plants. [source] Reservoir and Non-reservoir Hosts of Bean-Wilt Pathogen, Fusarium oxysporum f. sp. phaseoliJOURNAL OF PHYTOPATHOLOGY, Issue 7-8 2001O. D. Dhingra Abstract The capacity of Fusarium oxysporum f. sp. phaseoli to multiply in the roots of 12 non-host plant species was determined with the objective of selecting potential candidates for crop rotation and/or green manuring in infested bean fields. The plants were inoculated at the seedling stage by a benomyl-resistant mutant of the pathogen using the root-dip technique and transplanted to natural soil. The number of colony forming units/g dry root tissue (CFU/g) was determined at the full bloom stage. Quantitatively, the root colonization differed greatly among the plant species. The roots and lower stem of Dolichos lablab, Phaseolus lunatus, Mucuna aterrima, Canavalia ensiforme and Vigna unguiculata were the most compatible with the pathogen and those of Sorghum bicolor, Crotalaria juncea, Oryza sativa and Zea mays were least compatible. No disease symptoms developed on any plant species. Chlamydospore germination in the rhizosphere also differed significantly among the plant species. There was no correlation between percentage chlamydospore germination in the rhizosphere and extent of root colonization. Most plant species recommended for green manuring in bean fields allowed extensive root and stem colonization by F. o. f. sp. phaseoli and were considered as reservoir hosts. All three of the gramineous species tested and C. juncea were classed as non-reservoir host, because the pathogen did not colonize the stem and its multiplication in the roots was very low. These plant species appear to be good candidates for long-term field evaluation to determine their usefulness in an integrated management of Fusarium bean-wilt. [source] The Omnipresent Classroom during Summer Study Abroad: American Students in Conversation with Their French HostsMODERN LANGUAGE JOURNAL, Issue 2 2002Sharon Wilkinson Study abroad is often promoted as one of the best opportunities to use foreign language skills outside the classroom. Yet, relatively little is known about the language that students produce when speaking in noninstructional settings. Relying on conversation analysis and ethnographic techniques, this qualitative study investigates both speech and speaker perceptions through tape,recorded conversations between summer study abroad students and their French hosts, as well as through interviews and observations. Findings indicate that natives and nonnatives alike relied heavily on classroom roles and discourse structures to manage their interactions, calling into question the assumption that language use with a native,speaking host family liberates students from classroom limitations. The inappropriateness of transferring didactic discourse patterns to out,of,class interactions also raises issues for consideration about the nature of in,class instructional practices. [source] Strain-specific regulation of intracellular Wolbachia density in multiply infected insectsMOLECULAR ECOLOGY, Issue 12 2003L. Mouton Abstract Vertically transmitted symbionts suffer a severe reduction in numbers when they pass through host generations, resulting in genetic homogeneity or even clonality of their populations. Wolbachia endosymbionts that induce cytoplasmic incompatibility in their hosts depart from this rule, because cytoplasmic incompatibility actively maintains multiple infection within hosts. Hosts and symbionts are thus probably under peculiar selective pressures that must shape the way intracellular bacterial populations are regulated. We studied the density and location of Wolbachia within adult Leptopilina heterotoma, a haplodiploid wasp that is parasitic on Drosophila and that is naturally infected with three Wolbachia strains, but for which we also obtained one simply infected and two doubly infected lines. Comparison of these four lines by quantitative polymerase chain reaction using a real-time detection system showed that total Wolbachia density varies according to the infection status of individuals, while the specific density of each Wolbachia strain remains constant regardless of the presence of other strains. This suggests that Wolbachia strains do not compete with one another within the same host individual, and that a strain-specific regulatory mechanism is operating. We discuss the regulatory mechanisms that are involved, and how this process might have evolved as a response to selective pressures acting on both partners. [source] Potato spindle tuber viroid: the simplicity paradox resolved?MOLECULAR PLANT PATHOLOGY, Issue 5 2007ROBERT A. OWENS SUMMARY Taxonomy: , Potato spindle tuber viroid (PSTVd) is the type species of the genus Posipiviroid, family Pospiviroidae. An absence of hammerhead ribozymes and the presence of a ,central conserved region' distinguish PSTVd and related viroids from members of a second viroid family, the Avsunviroidae. Physical properties: , Viroids are small, unencapsidated, circular, single-stranded RNA molecules which replicate autonomously when inoculated into host plants. Because viroids are non-protein-coding RNAs, designation of the more abundant, highly infectious polarity strand as the positive strand is arbitrary. PSTVd assumes a rod-like, highly structured conformation that is resistant to nuclease degradation in vitro. Naturally occurring sequence variants of PSTVd range in size from 356 to 361 nt. Hosts and symptoms: , The natural host range of PSTVd,cultivated potato, certain other Solanum spp., and avocado,appears to be quite limited. Foliar symptoms in potato are often obscure, and the severity of tuber symptoms (elongation with the appearance of prominent bud scales/eyebrows and growth cracks) depends on both temperature and length of infection. PSTVd has a broad experimental host range, especially among solanaceous species, and strains are classified as mild, intermediate or severe based upon the symptoms observed in sensitive tomato cultivars. These symptoms include shortening of internodes, petioles and mid-ribs, severe epinasty and wrinkling of the leaves, and necrosis of mid-ribs, petioles and stems. [source] Turnip yellow mosaic virus: transfer RNA mimicry, chloroplasts and a C-rich genomeMOLECULAR PLANT PATHOLOGY, Issue 5 2004THEO W. DREHER SUMMARY Taxonomy:,Turnip yellow mosaic virus (TYMV) is the type species of the genus Tymovirus, family Tymoviridae. TYMV is a positive strand RNA virus of the alphavirus-like supergroup. Physical properties:, Virions are non-enveloped 28-nm T = 3 icosahedrons composed of a single 20-kDa coat protein that is clustered in 20 hexameric and 12 pentameric subunits. Infectious particles and empty capsids coexist in infected tissue. The genomic RNA is 6.3 kb long, with a 5,m7GpppG cap and a 3, untranslated region ending in a tRNA-like structure to which valine can be covalently added. The genome has a distinctive skewed C-rich, G-poor composition (39% C, 17% G). Viral proteins:, Two proteins, whose open reading frames extensively overlap, are translated from the genomic RNA. p206, which contains sequences indicative of RNA capping, NTPase/helicase and polymerase activities, is the only viral protein that is necessary for genome replication in single cells. It is produced as a polyprotein and self-cleaved to yield 141- and 66-kDa proteins. p69 is required for virus movement within the plant and is also a suppressor of gene silencing. The coat protein is expressed from the single subgenomic RNA. Hosts and symptoms:, TYMV has a narrow host range almost completely restricted to the Cruciferae. Experimental host species are Brassica pekinensis (Chinese cabbage) or B. rapa (turnip), in which diffuse chlorotic local lesions and systemic yellow mosaic symptoms appear. Arabidopsis thaliana can also be used. Clumping of chloroplasts and the accumulation of vesicular invaginations of the chloroplast outer membranes are distinctive cytopathological symptoms. High yields of virus are produced in all leaf tissues, and the virus is readily transmissible by mechanical inoculation. Localized transmission by flea beetles may occur in the field. [source] Black currant reversion virus, a mite-transmitted nepovirusMOLECULAR PLANT PATHOLOGY, Issue 3 2004Petri Susi SUMMARY Taxonomy: Black currant reversion virus (BRV) is the first identified mite-transmitted member of the genus Nepovirus (family Comoviridae). A few systematic studies have been performed to compare virus isolates from different geographical locations. Physical properties: Purified preparations contain two closely sedimenting centrifugal components (B and M for RNA1 and RNA2, respectively) at varying ratios, and occasionally a T component (for satellite RNA). The BRV capsids have a diameter of 27 nm and they are putatively composed of 60 copies of a single species of capsid (coat) protein assembled in an icosahedral lattice. Diluted plant sap loses its infectivity within 1 day at 20 °C and in 4,8 days at 4 °C. Hosts: The natural host range of BRV is limited; it infects black currant (Ribes nigrum L.) and some related Ribes species. The transmission of the virus is by the eriophyid gall mite of black currant (Cecidophyopsis ribis). A number of herbaceous plants can be infected experimentally. BRV is the agent of black currant reversion disease (BRD), which is economically the most significant virus disease in Ribes species. BRV and BRD occur widely in locations where black currant is cultivated commercially. [source] Root-knot nematode parasitism and host response: molecular basis of a sophisticated interactionMOLECULAR PLANT PATHOLOGY, Issue 4 2003Pierre Abad SUMMARY Taxonomy: Eukaryota; Metazoa; Nematoda; Chromadorea; order Tylenchida; Tylenchoidea; Heteroderidae; genus Meloidogyne. Physical properties: Microscopic-non-segmented worms. Meloidogyne species can reproduce by apomixis, facultative meiotic parthenogenesis or obligate mitotic parthenogenesis. Obligate biotrophic parasites inducing the re-differentiation of plant cells into specialized feeding cells. Hosts: Meloidogyne spp. can infest more than 3000 plant species including vegetables, fruit trees, cereals and ornamental flowers. Symptoms: Root swellings called galls. Alteration of the root vascular system. Disease control: Cultural control, chemical control, resistant cultivars. Agronomic importance: Major threat to agriculture in temperate and tropical regions. [source] Beet yellows virus: the importance of being differentMOLECULAR PLANT PATHOLOGY, Issue 2 2003Valerian V. Dolja SUMMARY Taxonomic relationship: Type member of the genus Closterovirus, family Closteroviridae. A member of the alphavirus-like supergroup of positive-strand RNA viruses. Physical properties: Virions are flexuous filaments of ,1300 nm in length and ,12 nm in diameter that are made up of a ,15.5 kb RNA and five proteins. The major capsid protein forms virion body of helical symmetry that constitutes ,95% of the virion length. The short virion tail is assembled by the minor capsid protein, Hsp70-homologue, ,64-kDa protein, and ,20-kDa protein. Viral proteins: The 5,-most ORFs 1a and 1b encode leader proteinase and RNA replicase. The remaining ORFs 2,8 are expressed by subgenomic mRNAs that encode 6-kDa membrane protein, Hsp70 homologue, ,64-kDa protein, minor and major capsid proteins, ,20-kDa protein, and ,21-kDa protein, respectively. Hosts: The principal crop plants affected by Beet yellows virus (BYV) are sugar beet (Beta vulgaris) and spinach (Spinacea oleracea). In addition, BYV was reported to infect ,120 species in 15 families. Most suitable propagation species are Nicotiana benthamiana, Tetragonia expansa, and Claytonia perfoliata. [source] Cauliflower mosaic virus: still in the newsMOLECULAR PLANT PATHOLOGY, Issue 6 2002Muriel Haas SUMMARY Taxonomic relationship:Cauliflower mosaic virus (CaMV) is the type member of the Caulimovirus genus in the Caulimoviridae family, which comprises five other genera. CaMV replicates its DNA genome by reverse transcription of a pregenomic RNA and thus belongs to the pararetrovirus supergroup, which includes the Hepadnaviridae family infecting vertebrates. Physical properties:, Virions are non-enveloped isometric particles, 53 nm in diameter (Fig. 1). They are constituted by 420 capsid protein subunits organized following T= 7 icosahedral symmetry (Cheng, R.H., Olson, N.H. and Baker, T.S. (1992) Cauliflower mosaic virus: a 420 subunit (T= 7), multilayer structure. Virology, 16, 655,668). The genome consists of a double-stranded circular DNA of approximately 8000 bp that is embedded in the inner surface of the capsid. Figure 1. Electron micrograph of CaMV virions. Courtesy of J. Menissier de Murcia, Ecole Supérieure de Biotechnologie de Strasbourg. Viral proteins: The CaMV genome encodes six proteins, a cell-to-cell movement protein (P1), two aphid transmission factors (P2 and P3), the precursor of the capsid proteins (P4), a polyprotein precursor of proteinase, reverse transcriptase and ribonuclease H (P5) and an inclusion body protein/translation transactivator (P6). Hosts: The host range of CaMV is limited to plants of the Cruciferae family, i.e. Brassicae species and Arabidopsis thaliana, but some viral strains can also infect solanaceous plants. In nature, CaMV is transmitted by aphids in a non-circulative manner. [source] European Mathematical Genetics Meeting, Heidelberg, Germany, 12th,13th April 2007ANNALS OF HUMAN GENETICS, Issue 4 2007Article first published online: 28 MAY 200 Saurabh Ghosh 11 Indian Statistical Institute, Kolkata, India High correlations between two quantitative traits may be either due to common genetic factors or common environmental factors or a combination of both. In this study, we develop statistical methods to extract the contribution of a common QTL to the total correlation between the components of a bivariate phenotype. Using data on bivariate phenotypes and marker genotypes for sib-pairs, we propose a test for linkage between a common QTL and a marker locus based on the conditional cross-sib trait correlations (trait 1 of sib 1 , trait 2 of sib 2 and conversely) given the identity-by-descent sharing at the marker locus. The null hypothesis cannot be rejected unless there exists a common QTL. We use Monte-Carlo simulations to evaluate the performance of the proposed test under different trait parameters and quantitative trait distributions. An application of the method is illustrated using data on two alcohol-related phenotypes from the Collaborative Study On The Genetics Of Alcoholism project. Rémi Kazma 1 , Catherine Bonaïti-Pellié 1 , Emmanuelle Génin 12 INSERM UMR-S535 and Université Paris Sud, Villejuif, 94817, France Keywords: Gene-environment interaction, sibling recurrence risk, exposure correlation Gene-environment interactions may play important roles in complex disease susceptibility but their detection is often difficult. Here we show how gene-environment interactions can be detected by investigating the degree of familial aggregation according to the exposure of the probands. In case of gene-environment interaction, the distribution of genotypes of affected individuals, and consequently the risk in relatives, depends on their exposure. We developed a test comparing the risks in sibs according to the proband exposure. To evaluate the properties of this new test, we derived the formulas for calculating the expected risks in sibs according to the exposure of probands for various values of exposure frequency, relative risk due to exposure alone, frequencies of latent susceptibility genotypes, genetic relative risks and interaction coefficients. We find that the ratio of risks when the proband is exposed and not exposed is a good indicator of the interaction effect. We evaluate the power of the test for various sample sizes of affected individuals. We conclude that this test is valuable for diseases with moderate familial aggregation, only when the role of the exposure has been clearly evidenced. Since a correlation for exposure among sibs might lead to a difference in risks among sibs in the different proband exposure strata, we also add an exposure correlation coefficient in the model. Interestingly, we find that when this correlation is correctly accounted for, the power of the test is not decreased and might even be significantly increased. Andrea Callegaro 1 , Hans J.C. Van Houwelingen 1 , Jeanine Houwing-Duistermaat 13 Dept. of Medical Statistics and Bioinformatics, Leiden University Medical Center, The Netherlands Keywords: Survival analysis, age at onset, score test, linkage analysis Non parametric linkage (NPL) analysis compares the identical by descent (IBD) sharing in sibling pairs to the expected IBD sharing under the hypothesis of no linkage. Often information is available on the marginal cumulative hazards (for example breast cancer incidence curves). Our aim is to extend the NPL methods by taking into account the age at onset of selected sibling pairs using these known marginal hazards. Li and Zhong (2002) proposed a (retrospective) likelihood ratio test based on an additive frailty model for genetic linkage analysis. From their model we derive a score statistic for selected samples which turns out to be a weighed NPL method. The weights depend on the marginal cumulative hazards and on the frailty parameter. A second approach is based on a simple gamma shared frailty model. Here, we simply test whether the score function of the frailty parameter depends on the excess IBD. We compare the performance of these methods using simulated data. Céline Bellenguez 1 , Carole Ober 2 , Catherine Bourgain 14 INSERM U535 and University Paris Sud, Villejuif, France 5 Department of Human Genetics, The University of Chicago, USA Keywords: Linkage analysis, linkage disequilibrium, high density SNP data Compared with microsatellite markers, high density SNP maps should be more informative for linkage analyses. However, because they are much closer, SNPs present important linkage disequilibrium (LD), which biases classical nonparametric multipoint analyses. This problem is even stronger in population isolates where LD extends over larger regions with a more stochastic pattern. We investigate the issue of linkage analysis with a 500K SNP map in a large and inbred 1840-member Hutterite pedigree, phenotyped for asthma. Using an efficient pedigree breaking strategy, we first identified linked regions with a 5cM microsatellite map, on which we focused to evaluate the SNP map. The only method that models LD in the NPL analysis is limited in both the pedigree size and the number of markers (Abecasis and Wigginton, 2005) and therefore could not be used. Instead, we studied methods that identify sets of SNPs with maximum linkage information content in our pedigree and no LD-driven bias. Both algorithms that directly remove pairs of SNPs in high LD and clustering methods were evaluated. Null simulations were performed to control that Zlr calculated with the SNP sets were not falsely inflated. Preliminary results suggest that although LD is strong in such populations, linkage information content slightly better than that of microsatellite maps can be extracted from dense SNP maps, provided that a careful marker selection is conducted. In particular, we show that the specific LD pattern requires considering LD between a wide range of marker pairs rather than only in predefined blocks. Peter Van Loo 1,2,3 , Stein Aerts 1,2 , Diether Lambrechts 4,5 , Bernard Thienpont 2 , Sunit Maity 4,5 , Bert Coessens 3 , Frederik De Smet 4,5 , Leon-Charles Tranchevent 3 , Bart De Moor 2 , Koen Devriendt 3 , Peter Marynen 1,2 , Bassem Hassan 1,2 , Peter Carmeliet 4,5 , Yves Moreau 36 Department of Molecular and Developmental Genetics, VIB, Belgium 7 Department of Human Genetics, University of Leuven, Belgium 8 Bioinformatics group, Department of Electrical Engineering, University of Leuven, Belgium 9 Department of Transgene Technology and Gene Therapy, VIB, Belgium 10 Center for Transgene Technology and Gene Therapy, University of Leuven, Belgium Keywords: Bioinformatics, gene prioritization, data fusion The identification of genes involved in health and disease remains a formidable challenge. Here, we describe a novel bioinformatics method to prioritize candidate genes underlying pathways or diseases, based on their similarity to genes known to be involved in these processes. It is freely accessible as an interactive software tool, ENDEAVOUR, at http://www.esat.kuleuven.be/endeavour. Unlike previous methods, ENDEAVOUR generates distinct prioritizations from multiple heterogeneous data sources, which are then integrated, or fused, into one global ranking using order statistics. ENDEAVOUR prioritizes candidate genes in a three-step process. First, information about a disease or pathway is gathered from a set of known "training" genes by consulting multiple data sources. Next, the candidate genes are ranked based on similarity with the training properties obtained in the first step, resulting in one prioritized list for each data source. Finally, ENDEAVOUR fuses each of these rankings into a single global ranking, providing an overall prioritization of the candidate genes. Validation of ENDEAVOUR revealed it was able to efficiently prioritize 627 genes in disease data sets and 76 genes in biological pathway sets, identify candidates of 16 mono- or polygenic diseases, and discover regulatory genes of myeloid differentiation. Furthermore, the approach identified YPEL1 as a novel gene involved in craniofacial development from a 2-Mb chromosomal region, deleted in some patients with DiGeorge-like birth defects. Finally, we are currently evaluating a pipeline combining array-CGH, ENDEAVOUR and in vivo validation in zebrafish to identify novel genes involved in congenital heart defects. Mark Broom 1 , Graeme Ruxton 2 , Rebecca Kilner 311 Mathematics Dept., University of Sussex, UK 12 Division of Environmental and Evolutionary Biology, University of Glasgow, UK 13 Department of Zoology, University of Cambridge, UK Keywords: Evolutionarily stable strategy, parasitism, asymmetric game Brood parasites chicks vary in the harm that they do to their companions in the nest. In this presentation we use game-theoretic methods to model this variation. Our model considers hosts which potentially abandon single nestlings and instead choose to re-allocate their reproductive effort to future breeding, irrespective of whether the abandoned chick is the host's young or a brood parasite's. The parasite chick must decide whether or not to kill host young by balancing the benefits from reduced competition in the nest against the risk of desertion by host parents. The model predicts that three different types of evolutionarily stable strategies can exist. (1) Hosts routinely rear depleted broods, the brood parasite always kills host young and the host never then abandons the nest. (2) When adult survival after deserting single offspring is very high, hosts always abandon broods of a single nestling and the parasite never kills host offspring, effectively holding them as hostages to prevent nest desertion. (3) Intermediate strategies, in which parasites sometimes kill their nest-mates and host parents sometimes desert nests that contain only a single chick, can also be evolutionarily stable. We provide quantitative descriptions of how the values given to ecological and behavioral parameters of the host-parasite system influence the likelihood of each strategy and compare our results with real host-brood parasite associations in nature. Martin Harrison 114 Mathematics Dept, University of Sussex, UK Keywords: Brood parasitism, games, host, parasite The interaction between hosts and parasites in bird populations has been studied extensively. Game theoretical methods have been used to model this interaction previously, but this has not been studied extensively taking into account the sequential nature of this game. We consider a model allowing the host and parasite to make a number of decisions, which depend on a number of natural factors. The host lays an egg, a parasite bird will arrive at the nest with a certain probability and then chooses to destroy a number of the host eggs and lay one of it's own. With some destruction occurring, either natural or through the actions of the parasite, the host chooses to continue, eject an egg (hoping to eject the parasite) or abandon the nest. Once the eggs have hatched the game then falls to the parasite chick versus the host. The chick chooses to destroy or eject a number of eggs. The final decision is made by the host, choosing whether to raise or abandon the chicks that are in the nest. We consider various natural parameters and probabilities which influence these decisions. We then use this model to look at real-world situations of the interactions of the Reed Warbler and two different parasites, the Common Cuckoo and the Brown-Headed Cowbird. These two parasites have different methods in the way that they parasitize the nests of their hosts. The hosts in turn have a different reaction to these parasites. Arne Jochens 1 , Amke Caliebe 2 , Uwe Roesler 1 , Michael Krawczak 215 Mathematical Seminar, University of Kiel, Germany 16 Institute of Medical Informatics and Statistics, University of Kiel, Germany Keywords: Stepwise mutation model, microsatellite, recursion equation, temporal behaviour We consider the stepwise mutation model which occurs, e.g., in microsatellite loci. Let X(t,i) denote the allelic state of individual i at time t. We compute expectation, variance and covariance of X(t,i), i=1,,,N, and provide a recursion equation for P(X(t,i)=z). Because the variance of X(t,i) goes to infinity as t grows, for the description of the temporal behaviour, we regard the scaled process X(t,i)-X(t,1). The results furnish a better understanding of the behaviour of the stepwise mutation model and may in future be used to derive tests for neutrality under this model. Paul O'Reilly 1 , Ewan Birney 2 , David Balding 117 Statistical Genetics, Department of Epidemiology and Public Health, Imperial, College London, UK 18 European Bioinformatics Institute, EMBL, Cambridge, UK Keywords: Positive selection, Recombination rate, LD, Genome-wide, Natural Selection In recent years efforts to develop population genetics methods that estimate rates of recombination and levels of natural selection in the human genome have intensified. However, since the two processes have an intimately related impact on genetic variation their inference is vulnerable to confounding. Genomic regions subject to recent selection are likely to have a relatively recent common ancestor and consequently less opportunity for historical recombinations that are detectable in contemporary populations. Here we show that selection can reduce the population-based recombination rate estimate substantially. In genome-wide studies for detecting selection we observe a tendency to highlight loci that are subject to low levels of recombination. We find that the outlier approach commonly adopted in such studies may have low power unless variable recombination is accounted for. We introduce a new genome-wide method for detecting selection that exploits the sensitivity to recent selection of methods for estimating recombination rates, while accounting for variable recombination using pedigree data. Through simulations we demonstrate the high power of the Ped/Pop approach to discriminate between neutral and adaptive evolution, particularly in the context of choosing outliers from a genome-wide distribution. Although methods have been developed showing good power to detect selection ,in action', the corresponding window of opportunity is small. In contrast, the power of the Ped/Pop method is maintained for many generations after the fixation of an advantageous variant Sarah Griffiths 1 , Frank Dudbridge 120 MRC Biostatistics Unit, Cambridge, UK Keywords: Genetic association, multimarker tag, haplotype, likelihood analysis In association studies it is generally too expensive to genotype all variants in all subjects. We can exploit linkage disequilibrium between SNPs to select a subset that captures the variation in a training data set obtained either through direct resequencing or a public resource such as the HapMap. These ,tag SNPs' are then genotyped in the whole sample. Multimarker tagging is a more aggressive adaptation of pairwise tagging that allows for combinations of two or more tag SNPs to predict an untyped SNP. Here we describe a new method for directly testing the association of an untyped SNP using a multimarker tag. Previously, other investigators have suggested testing a specific tag haplotype, or performing a weighted analysis using weights derived from the training data. However these approaches do not properly account for the imperfect correlation between the tag haplotype and the untyped SNP. Here we describe a straightforward approach to testing untyped SNPs using a missing-data likelihood analysis, including the tag markers as nuisance parameters. The training data is stacked on top of the main body of genotype data so there is information on how the tag markers predict the genotype of the untyped SNP. The uncertainty in this prediction is automatically taken into account in the likelihood analysis. This approach yields more power and also a more accurate prediction of the odds ratio of the untyped SNP. Anke Schulz 1 , Christine Fischer 2 , Jenny Chang-Claude 1 , Lars Beckmann 121 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany 22 Institute of Human Genetics, University of Heidelberg, Germany Keywords: Haplotype, haplotype sharing, entropy, Mantel statistics, marker selection We previously introduced a new method to map genes involved in complex diseases, using haplotype sharing-based Mantel statistics to correlate genetic and phenotypic similarity. Although the Mantel statistic is powerful in narrowing down candidate regions, the precise localization of a gene is hampered in genomic regions where linkage disequilibrium is so high that neighboring markers are found to be significant at similar magnitude and we are not able to discriminate between them. Here, we present a new approach to localize susceptibility genes by combining haplotype sharing-based Mantel statistics with an iterative entropy-based marker selection algorithm. For each marker at which the Mantel statistic is evaluated, the algorithm selects a subset of surrounding markers. The subset is chosen to maximize multilocus linkage disequilibrium, which is measured by the normalized entropy difference introduced by Nothnagel et al. (2002). We evaluated the algorithm with respect to type I error and power. Its ability to localize the disease variant was compared to the localization (i) without marker selection and (ii) considering haplotype block structure. Case-control samples were simulated from a set of 18 haplotypes, consisting of 15 SNPs in two haplotype blocks. The new algorithm gave correct type I error and yielded similar power to detect the disease locus compared to the alternative approaches. The neighboring markers were clearly less often significant than the causal locus, and also less often significant compared to the alternative approaches. Thus the new algorithm improved the precision of the localization of susceptibility genes. Mark M. Iles 123 Section of Epidemiology and Biostatistics, LIMM, University of Leeds, UK Keywords: tSNP, tagging, association, HapMap Tagging SNPs (tSNPs) are commonly used to capture genetic diversity cost-effectively. However, it is important that the efficacy of tSNPs is correctly estimated, otherwise coverage may be insufficient. If the pilot sample from which tSNPs are chosen is too small or the initial marker map too sparse, tSNP efficacy may be overestimated. An existing estimation method based on bootstrapping goes some way to correct for insufficient sample size and overfitting, but does not completely solve the problem. We describe a novel method, based on exclusion of haplotypes, that improves on the bootstrap approach. Using simulated data, the extent of the sample size problem is investigated and the performance of the bootstrap and the novel method are compared. We incorporate an existing method adjusting for marker density by ,SNP-dropping'. We find that insufficient sample size can cause large overestimates in tSNP efficacy, even with as many as 100 individuals, and the problem worsens as the region studied increases in size. Both the bootstrap and novel method correct much of this overestimate, with our novel method consistently outperforming the bootstrap method. We conclude that a combination of insufficient sample size and overfitting may lead to overestimation of tSNP efficacy and underpowering of studies based on tSNPs. Our novel approach corrects for much of this bias and is superior to the previous method. Sample sizes larger than previously suggested may still be required for accurate estimation of tSNP efficacy. This has obvious ramifications for the selection of tSNPs from HapMap data. Claudio Verzilli 1 , Juliet Chapman 1 , Aroon Hingorani 2 , Juan Pablo-Casas 1 , Tina Shah 2 , Liam Smeeth 1 , John Whittaker 124 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, UK 25 Division of Medicine, University College London, UK Keywords: Meta-analysis, Genetic association studies We present a Bayesian hierarchical model for the meta-analysis of candidate gene studies with a continuous outcome. Such studies often report results from association tests for different, possibly study-specific and non-overlapping markers (typically SNPs) in the same genetic region. Meta analyses of the results at each marker in isolation are seldom appropriate as they ignore the correlation that may exist between markers due to linkage disequlibrium (LD) and cannot assess the relative importance of variants at each marker. Also such marker-wise meta analyses are restricted to only those studies that have typed the marker in question, with a potential loss of power. A better strategy is one which incorporates information about the LD between markers so that any combined estimate of the effect of each variant is corrected for the effect of other variants, as in multiple regression. Here we develop a Bayesian hierarchical linear regression that models the observed genotype group means and uses pairwise LD measurements between markers as prior information to make posterior inference on adjusted effects. The approach is applied to the meta analysis of 24 studies assessing the effect of 7 variants in the C-reactive protein (CRP) gene region on plasma CRP levels, an inflammatory biomarker shown in observational studies to be positively associated with cardiovascular disease. Cathryn M. Lewis 1 , Christopher G. Mathew 1 , Theresa M. Marteau 226 Dept. of Medical and Molecular Genetics, King's College London, UK 27 Department of Psychology, King's College London, UK Keywords: Risk, genetics, CARD15, smoking, model Recently progress has been made in identifying mutations that confer susceptibility to complex diseases, with the potential to use these mutations in determining disease risk. We developed methods to estimate disease risk based on genotype relative risks (for a gene G), exposure to an environmental factor (E), and family history (with recurrence risk ,R for a relative of type R). ,R must be partitioned into the risk due to G (which is modelled independently) and the residual risk. The risk model was then applied to Crohn's disease (CD), a severe gastrointestinal disease for which smoking increases disease risk approximately 2-fold, and mutations in CARD15 confer increased risks of 2.25 (for carriers of a single mutation) and 9.3 (for carriers of two mutations). CARD15 accounts for only a small proportion of the genetic component of CD, with a gene-specific ,S, CARD15 of 1.16, from a total sibling relative risk of ,S= 27. CD risks were estimated for high-risk individuals who are siblings of a CD case, and who also smoke. The CD risk to such individuals who carry two CARD15 mutations is approximately 0.34, and for those carrying a single CARD15 mutation the risk is 0.08, compared to a population prevalence of approximately 0.001. These results imply that complex disease genes may be valuable in estimating with greater precision than has hitherto been possible disease risks in specific, easily identified subgroups of the population with a view to prevention. Yurii Aulchenko 128 Department of Epidemiology & Biostatistics, Erasmus Medical Centre Rotterdam, The Netherlands Keywords: Compression, information, bzip2, genome-wide SNP data, statistical genetics With advances in molecular technology, studies accessing millions of genetic polymorphisms in thousands of study subjects will soon become common. Such studies generate large amounts of data, whose effective storage and management is a challenge to the modern statistical genetics. Standard file compression utilities, such as Zip, Gzip and Bzip2, may be helpful to minimise the storage requirements. Less obvious is the fact that the data compression techniques may be also used in the analysis of genetic data. It is known that the efficiency of a particular compression algorithm depends on the probability structure of the data. In this work, we compared different standard and customised tools using the data from human HapMap project. Secondly, we investigate the potential uses of data compression techniques for the analysis of linkage, association and linkage disequilibrium Suzanne Leal 1 , Bingshan Li 129 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA Keywords: Consanguineous pedigrees, missing genotype data Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al (2005) that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. The false-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. Which family members will aid in the reduction of false-positive evidence of linkage is highly dependent on which other family members are genotyped. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. When parental genotypes are not available, false-positive evidence for linkage can be reduced by including in the analysis genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents. Najaf Amin 1 , Yurii Aulchenko 130 Department of Epidemiology & Biostatistics, Erasmus Medical Centre Rotterdam, The Netherlands Keywords: Genomic Control, pedigree structure, quantitative traits The Genomic Control (GC) method was originally developed to control for population stratification and cryptic relatedness in association studies. This method assumes that the effect of population substructure on the test statistics is essentially constant across the genome, and therefore unassociated markers can be used to estimate the effect of confounding onto the test statistic. The properties of GC method were extensively investigated for different stratification scenarios, and compared to alternative methods, such as the transmission-disequilibrium test. The potential of this method to correct not for occasional cryptic relations, but for regular pedigree structure, however, was not investigated before. In this work we investigate the potential of the GC method for pedigree-based association analysis of quantitative traits. The power and type one error of the method was compared to standard methods, such as the measured genotype (MG) approach and quantitative trait transmission-disequilibrium test. In human pedigrees, with trait heritability varying from 30 to 80%, the power of MG and GC approach was always higher than that of TDT. GC had correct type 1 error and its power was close to that of MG under moderate heritability (30%), but decreased with higher heritability. William Astle 1 , Chris Holmes 2 , David Balding 131 Department of Epidemiology and Public Health, Imperial College London, UK 32 Department of Statistics, University of Oxford, UK Keywords: Population structure, association studies, genetic epidemiology, statistical genetics In the analysis of population association studies, Genomic Control (Devlin & Roeder, 1999) (GC) adjusts the Armitage test statistic to correct the type I error for the effects of population substructure, but its power is often sub-optimal. Turbo Genomic Control (TGC) generalises GC to incorporate co-variation of relatedness and phenotype, retaining control over type I error while improving power. TGC is similar to the method of Yu et al. (2006), but we extend it to binary (case-control) in addition to quantitative phenotypes, we implement improved estimation of relatedness coefficients, and we derive an explicit statistic that generalizes the Armitage test statistic and is fast to compute. TGC also has similarities to EIGENSTRAT (Price et al., 2006) which is a new method based on principle components analysis. The problems of population structure(Clayton et al., 2005) and cryptic relatedness (Voight & Pritchard, 2005) are essentially the same: if patterns of shared ancestry differ between cases and controls, whether distant (coancestry) or recent (cryptic relatedness), false positives can arise and power can be diminished. With large numbers of widely-spaced genetic markers, coancestry can now be measured accurately for each pair of individuals via patterns of allele-sharing. Instead of modelling subpopulations, we work instead with a coancestry coefficient for each pair of individuals in the study. We explain the relationships between TGC, GC and EIGENSTRAT. We present simulation studies and real data analyses to illustrate the power advantage of TGC in a range of scenarios incorporating both substructure and cryptic relatedness. References Clayton, D. G.et al. (2005) Population structure, differential bias and genomic control in a large-scale case-control association study. Nature Genetics37(11) November 2005. Devlin, B. & Roeder, K. (1999) Genomic control for association studies. Biometics55(4) December 1999. Price, A. L.et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics38(8) (August 2006). Voight, B. J. & Pritchard, J. K. (2005) Confounding from cryptic relatedness in case-control association studies. Public Library of Science Genetics1(3) September 2005. Yu, J.et al. (2006) A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nature Genetics38(2) February 2006. Hervé Perdry 1 , Marie-Claude Babron 1 , Françoise Clerget-Darpoux 133 INSERM U535 and Univ. Paris Sud, UMR-S 535, Villejuif, France Keywords: Modifier genes, case-parents trios, ordered transmission disequilibrium test A modifying locus is a polymorphic locus, distinct from the disease locus, which leads to differences in the disease phenotype, either by modifying the penetrance of the disease allele, or by modifying the expression of the disease. The effect of such a locus is a clinical heterogeneity that can be reflected by the values of an appropriate covariate, such as the age of onset, or the severity of the disease. We designed the Ordered Transmission Disequilibrium Test (OTDT) to test for a relation between the clinical heterogeneity, expressed by the covariate, and marker genotypes of a candidate gene. The method applies to trio families with one affected child and his parents. Each family member is genotyped at a bi-allelic marker M of a candidate gene. To each of the families is associated a covariate value; the families are ordered on the values of this covariate. As the TDT (Spielman et al. 1993), the OTDT is based on the observation of the transmission rate T of a given allele at M. The OTDT aims to find a critical value of the covariate which separates the sample of families in two subsamples in which the transmission rates are significantly different. We investigate the power of the method by simulations under various genetic models and covariate distributions. Acknowledgments H Perdry is funded by ARSEP. Pascal Croiseau 1 , Heather Cordell 2 , Emmanuelle Génin 134 INSERM U535 and University Paris Sud, UMR-S535, Villejuif, France 35 Institute of Human Genetics, Newcastle University, UK Keywords: Association, missing data, conditionnal logistic regression Missing data is an important problem in association studies. Several methods used to test for association need that individuals be genotyped at the full set of markers. Individuals with missing data need to be excluded from the analysis. This could involve an important decrease in sample size and a loss of information. If the disease susceptibility locus (DSL) is poorly typed, it is also possible that a marker in linkage disequilibrium gives a stronger association signal than the DSL. One may then falsely conclude that the marker is more likely to be the DSL. We recently developed a Multiple Imputation method to infer missing data on case-parent trios Starting from the observed data, a few number of complete data sets are generated by Markov-Chain Monte Carlo approach. These complete datasets are analysed using standard statistical package and the results are combined as described in Little & Rubin (2002). Here we report the results of simulations performed to examine, for different patterns of missing data, how often the true DSL gives the highest association score among different loci in LD. We found that multiple imputation usually correctly detect the DSL site even if the percentage of missing data is high. This is not the case for the naïve approach that consists in discarding trios with missing data. In conclusion, Multiple imputation presents the advantage of being easy to use and flexible and is therefore a promising tool in the search for DSL involved in complex diseases. Salma Kotti 1 , Heike Bickeböller 2 , Françoise Clerget-Darpoux 136 University Paris Sud, UMR-S535, Villejuif, France 37 Department of Genetic Epidemiology, Medical School, University of Göttingen, Germany Keywords: Genotype relative risk, internal controls, Family based analyses Family based analyses using internal controls are very popular both for detecting the effect of a genetic factor and for estimating the relative disease risk on the corresponding genotypes. Two different procedures are often applied to reconstitute internal controls. The first one considers one pseudocontrol genotype formed by the parental non-transmitted alleles called also 1:1 matching of alleles, while the second corresponds to three pseudocontrols corresponding to all genotypes formed by the parental alleles except the one of the case (1:3 matching). Many studies have compared between the two procedures in terms of the power and have concluded that the difference depends on the underlying genetic model and the allele frequencies. However, the estimation of the Genotype Relative Risk (GRR) under the two procedures has not been studied. Based on the fact that on the 1:1 matching, the control group is composed of the alleles untransmitted to the affected child and on the 1:3 matching, the control group is composed amongst alleles already transmitted to the affected child, we expect a difference on the GRR estimation. In fact, we suspect that the second procedure leads to biased estimation of the GRRs. We will analytically derive the GRR estimators for the 1:1 and 1:3 matching and will present the results at the meeting. Family based analyses using internal controls are very popular both for detecting the effect of a genetic factor and for estimating the relative disease risk on the corresponding genotypes. Two different procedures are often applied to reconstitute internal controls. The first one considers one pseudocontrol genotype formed by the parental non-transmitted alleles called also 1:1 matching of alleles, while the second corresponds to three pseudocontrols corresponding to all genotypes formed by the parental alleles except the one of the case (1:3 matching). Many studies have compared between the two procedures in terms of the power and have concluded that the difference depends on the underlying genetic model and the allele frequencies. However, the estimation of the Genotype Relative Risk (GRR) under the two procedures has not been studied. Based on the fact that on the 1:1 matching, the control group is composed of the alleles untransmitted to the affected child and on the 1:3 matching, the control group is composed amongst alleles already transmitted to the affected child, we expect a difference on the GRR estimation. In fact, we suspect that the second procedure leads to biased estimation of the GRR. We will analytically derive the GRR estimator for the 1:1 and 1:3 matching and will present the results at the meeting. Luigi Palla 1 , David Siegmund 239 Department of Mathematics,Free University Amsterdam, The Netherlands 40 Department of Statistics, Stanford University, California, USA Keywords: TDT, assortative mating, inbreeding, statistical power A substantial amount of Assortative Mating (AM) is often recorded on physical and psychological, dichotomous as well as quantitative traits that are supposed to have a multifactorial genetic component. In particular AM has the effect of increasing the genetic variance, even more than inbreeding because it acts across loci beside within loci, when the trait has a multifactorial origin. Under the assumption of a polygenic model for AM dating back to Wright (1921) and refined by Crow and Felsenstein (1968,1982), the effect of assortative mating on the power to detect genetic association in the Transmission Disequilibrium Test (TDT) is explored as parameters, such as the effective number of genes and the allelic frequency vary. The power is reflected by the non centrality parameter of the TDT and is expressed as a function of the number of trios, the relative risk of the heterozygous genotype and the allele frequency (Siegmund and Yakir, 2007). The noncentrality parameter of the relevant score statistic is updated considering the effect of AM which is expressed in terms of an ,effective' inbreeding coefficient. In particular, for dichotomous traits it is apparent that the higher the number of genes involved in the trait, the lower the loss in power due to AM. Finally an attempt is made to extend this relation to the Q-TDT (Rabinowitz, 1997), which involves considering the effect of AM also on the phenotypic variance of the trait of interest, under the assumption that AM affects only its additive genetic component. References Crow, & Felsenstein, (1968). The effect of assortative mating on the genetic composition of a population. Eugen.Quart.15, 87,97. Rabinowitz,, 1997. A Transmission Disequilibrium Test for Quantitative Trait Loci. Human Heredity47, 342,350. Siegmund, & Yakir, (2007) Statistics of gene mapping, Springer. Wright, (1921). System of mating.III. Assortative mating based on somatic resemblance. Genetics6, 144,161. Jérémie Nsengimana 1 , Ben D Brown 2 , Alistair S Hall 2 , Jenny H Barrett 141 Leeds Institute of Molecular Medicine, University of Leeds, UK 42 Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, UK Keywords: Inflammatory genes, haplotype, coronary artery disease Genetic Risk of Acute Coronary Events (GRACE) is an initiative to collect cases of coronary artery disease (CAD) and their unaffected siblings in the UK and to use them to map genetic variants increasing disease risk. The aim of the present study was to test the association between CAD and 51 single nucleotide polymorphisms (SNPs) and their haplotypes from 35 inflammatory genes. Genotype data were available for 1154 persons affected before age 66 (including 48% before age 50) and their 1545 unaffected siblings (891 discordant families). Each SNP was tested for association to CAD, and haplotypes within genes or gene clusters were tested using FBAT (Rabinowitz & Laird, 2000). For the most significant results, genetic effect size was estimated using conditional logistic regression (CLR) within STATA adjusting for other risk factors. Haplotypes were assigned using HAPLORE (Zhang et al., 2005), which considers all parental mating types consistent with offspring genotypes and assigns them a probability of occurence. This probability was used in CLR to weight the haplotypes. In the single SNP analysis, several SNPs showed some evidence for association, including one SNP in the interleukin-1A gene. Analysing haplotypes in the interleukin-1 gene cluster, a common 3-SNP haplotype was found to increase the risk of CAD (P = 0.009). In an additive genetic model adjusting for covariates the odds ratio (OR) for this haplotype is 1.56 (95% CI: 1.16-2.10, p = 0.004) for early-onset CAD (before age 50). This study illustrates the utility of haplotype analysis in family-based association studies to investigate candidate genes. References Rabinowitz, D. & Laird, N. M. (2000) Hum Hered50, 211,223. Zhang, K., Sun, F. & Zhao, H. (2005) Bioinformatics21, 90,103. Andrea Foulkes 1 , Recai Yucel 1 , Xiaohong Li 143 Division of Biostatistics, University of Massachusetts, USA Keywords: Haploytpe, high-dimensional, mixed modeling The explosion of molecular level information coupled with large epidemiological studies presents an exciting opportunity to uncover the genetic underpinnings of complex diseases; however, several analytical challenges remain to be addressed. Characterizing the components to complex diseases inevitably requires consideration of synergies across multiple genetic loci and environmental and demographic factors. In addition, it is critical to capture information on allelic phase, that is whether alleles within a gene are in cis (on the same chromosome) or in trans (on different chromosomes.) In associations studies of unrelated individuals, this alignment of alleles within a chromosomal copy is generally not observed. We address the potential ambiguity in allelic phase in this high dimensional data setting using mixed effects models. Both a semi-parametric and fully likelihood-based approach to estimation are considered to account for missingness in cluster identifiers. In the first case, we apply a multiple imputation procedure coupled with a first stage expectation maximization algorithm for parameter estimation. A bootstrap approach is employed to assess sensitivity to variability induced by parameter estimation. Secondly, a fully likelihood-based approach using an expectation conditional maximization algorithm is described. Notably, these models allow for characterizing high-order gene-gene interactions while providing a flexible statistical framework to account for the confounding or mediating role of person specific covariates. The proposed method is applied to data arising from a cohort of human immunodeficiency virus type-1 (HIV-1) infected individuals at risk for therapy associated dyslipidemia. Simulation studies demonstrate reasonable power and control of family-wise type 1 error rates. Vivien Marquard 1 , Lars Beckmann 1 , Jenny Chang-Claude 144 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany Keywords: Genotyping errors, type I error, haplotype-based association methods It has been shown in several simulation studies that genotyping errors may have a great impact on the type I error of statistical methods used in genetic association analysis of complex diseases. Our aim was to investigate type I error rates in a case-control study, when differential and non-differential genotyping errors were introduced in realistic scenarios. We simulated case-control data sets, where individual genotypes were drawn from a haplotype distribution of 18 haplotypes with 15 markers in the APM1 gene. Genotyping errors were introduced following the unrestricted and symmetric with 0 edges error models described by Heid et al. (2006). In six scenarios, errors resulted from changes of one allele to another with predefined probabilities of 1%, 2.5% or 10%, respectively. A multiple number of errors per haplotype was possible and could vary between 0 and 15, the number of markers investigated. We examined three association methods: Mantel statistics using haplotype-sharing; a haplotype-specific score test; and Armitage trend test for single markers. The type I error rates were not influenced for any of all the three methods for a genotyping error rate of less than 1%. For higher error rates and differential errors, the type I error of the Mantel statistic was only slightly and of the Armitage trend test moderately increased. The type I error rates of the score test were highly increased. The type I error rates were correct for all three methods for non-differential errors. Further investigations will be carried out with different frequencies of differential error rates and focus on power. Arne Neumann 1 , Dörthe Malzahn 1 , Martina Müller 2 , Heike Bickeböller 145 Department of Genetic Epidemiology, Medical School, University of Göttingen, Germany 46 GSF-National Research Center for Environment and Health, Neuherberg & IBE-Institute of Epidemiology, Ludwig-Maximilians University München, Germany Keywords: Interaction, longitudinal, nonparametric Longitudinal data show the time dependent course of phenotypic traits. In this contribution, we consider longitudinal cohort studies and investigate the association between two candidate genes and a dependent quantitative longitudinal phenotype. The set-up defines a factorial design which allows us to test simultaneously for the overall gene effect of the loci as well as for possible gene-gene and gene time interaction. The latter would induce genetically based time-profile differences in the longitudinal phenotype. We adopt a non-parametric statistical test to genetic epidemiological cohort studies and investigate its performance by simulation studies. The statistical test was originally developed for longitudinal clinical studies (Brunner, Munzel, Puri, 1999 J Multivariate Anal 70:286-317). It is non-parametric in the sense that no assumptions are made about the underlying distribution of the quantitative phenotype. Longitudinal observations belonging to the same individual can be arbitrarily dependent on one another for the different time points whereas trait observations of different individuals are independent. The two loci are assumed to be statistically independent. Our simulations show that the nonparametric test is comparable with ANOVA in terms of power of detecting gene-gene and gene-time interaction in an ANOVA favourable setting. Rebecca Hein 1 , Lars Beckmann 1 , Jenny Chang-Claude 147 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany Keywords: Indirect association studies, interaction effects, linkage disequilibrium, marker allele frequency Association studies accounting for gene-environment interactions (GxE) may be useful for detecting genetic effects and identifying important environmental effect modifiers. Current technology facilitates very dense marker spacing in genetic association studies; however, the true disease variant(s) may not be genotyped. In this situation, an association between a gene and a phenotype may still be detectable, using genetic markers associated with the true disease variant(s) (indirect association). Zondervan and Cardon [2004] showed that the odds ratios (OR) of markers which are associated with the disease variant depend highly on the linkage disequilibrium (LD) between the variant and the markers, and whether the allele frequencies match and thereby influence the sample size needed to detect genetic association. We examined the influence of LD and allele frequencies on the sample size needed to detect GxE in indirect association studies, and provide tables for sample size estimation. For discordant allele frequencies and incomplete LD, sample sizes can be unfeasibly large. The influence of both factors is stronger for disease loci with small rather than moderate to high disease allele frequencies. A decline in D' of e.g. 5% has less impact on sample size than increasing the difference in allele frequencies by the same percentage. Assuming 80% power, large interaction effects can be detected using smaller sample sizes than those needed for the detection of main effects. The detection of interaction effects involving rare alleles may not be possible. Focussing only on marker density can be a limited strategy in indirect association studies for GxE. Cyril Dalmasso 1 , Emmanuelle Génin 2 , Catherine Bourgain 2 , Philippe Broët 148 JE 2492 , Univ. Paris-Sud, France 49 INSERM UMR-S 535 and University Paris Sud, Villejuif, France Keywords: Linkage analysis, Multiple testing, False Discovery Rate, Mixture model In the context of genome-wide linkage analyses, where a large number of statistical tests are simultaneously performed, the False Discovery Rate (FDR) that is defined as the expected proportion of false discoveries among all discoveries is nowadays widely used for taking into account the multiple testing problem. Other related criteria have been considered such as the local False Discovery Rate (lFDR) that is a variant of the FDR giving to each test its own measure of significance. The lFDR is defined as the posterior probability that a null hypothesis is true. Most of the proposed methods for estimating the lFDR or the FDR rely on distributional assumption under the null hypothesis. However, in observational studies, the empirical null distribution may be very different from the theoretical one. In this work, we propose a mixture model based approach that provides estimates of the lFDR and the FDR in the context of large-scale variance component linkage analyses. In particular, this approach allows estimating the empirical null distribution, this latter being a key quantity for any simultaneous inference procedure. The proposed method is applied on a real dataset. Arief Gusnanto 1 , Frank Dudbridge 150 MRC Biostatistics Unit, Cambridge UK Keywords: Significance, genome-wide, association, permutation, multiplicity Genome-wide association scans have introduced statistical challenges, mainly in the multiplicity of thousands of tests. The question of what constitutes a significant finding remains somewhat unresolved. Permutation testing is very time-consuming, whereas Bayesian arguments struggle to distinguish direct from indirect association. It seems attractive to summarise the multiplicity in a simple form that allows users to avoid time-consuming permutations. A standard significance level would facilitate reporting of results and reduce the need for permutation tests. This is potentially important because current scans do not have full coverage of the whole genome, and yet, the implicit multiplicity is genome-wide. We discuss some proposed summaries, with reference to the empirical null distribution of the multiple tests, approximated through a large number of random permutations. Using genome-wide data from the Wellcome Trust Case-Control Consortium, we use a sub-sampling approach with increasing density to estimate the nominal p-value to obtain family-wise significance of 5%. The results indicate that the significance level is converging to about 1e-7 as the marker spacing becomes infinitely dense. We considered the concept of an effective number of independent tests, and showed that when used in a Bonferroni correction, the number varies with the overall significance level, but is roughly constant in the region of interest. We compared several estimators of the effective number of tests, and showed that in the region of significance of interest, Patterson's eigenvalue based estimator gives approximately the right family-wise error rate. Michael Nothnagel 1 , Amke Caliebe 1 , Michael Krawczak 151 Institute of Medical Informatics and Statistics, University Clinic Schleswig-Holstein, University of Kiel, Germany Keywords: Association scans, Bayesian framework, posterior odds, genetic risk, multiplicative model Whole-genome association scans have been suggested to be a cost-efficient way to survey genetic variation and to map genetic disease factors. We used a Bayesian framework to investigate the posterior odds of a genuine association under multiplicative disease models. We demonstrate that the p value alone is not a sufficient means to evaluate the findings in association studies. We suggest that likelihood ratios should accompany p values in association reports. We argue, that, given the reported results of whole-genome scans, more associations should have been successfully replicated if the consistently made assumptions about considerable genetic risks were correct. We conclude that it is very likely that the vast majority of relative genetic risks are only of the order of 1.2 or lower. Clive Hoggart 1 , Maria De Iorio 1 , John Whittakker 2 , David Balding 152 Department of Epidemiology and Public Health, Imperial College London, UK 53 Department of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, UK Keywords: Genome-wide association analyses, shrinkage priors, Lasso Testing one SNP at a time does not fully realise the potential of genome-wide association studies to identify multiple causal variants of small effect, which is a plausible scenario for many complex diseases. Moreover, many simulation studies assume a single causal variant and so more complex realities are ignored. Analysing large numbers of variants simultaneously is now becoming feasible, thanks to developments in Bayesian stochastic search methods. We pose the problem of SNP selection as variable selection in a regression model. In contrast to single SNP tests this approach simultaneously models the effect of all SNPs. SNPs are selected by a Bayesian interpretation of the lasso (Tibshirani, 1996); the maximum a posterior (MAP) estimate of the regression coefficients, which have been given independent, double exponential prior distributions. The double exponential distribution is an example of a shrinkage prior, MAP estimates with shrinkage priors can be zero, thus all SNPs with non zero regression coefficients are selected. In addition to the commonly-used double exponential (Laplace) prior, we also implement the normal exponential gamma prior distribution. We show that use of the Laplace prior improves SNP selection in comparison with single -SNP tests, and that the normal exponential gamma prior leads to a further improvement. Our method is fast and can handle very large numbers of SNPs: we demonstrate its performance using both simulated and real genome-wide data sets with 500 K SNPs, which can be analysed in 2 hours on a desktop workstation. Mickael Guedj 1,2 , Jerome Wojcik 2 , Gregory Nuel 154 Laboratoire Statistique et Génome, Université d'Evry, Evry France 55 Serono Pharmaceutical Research Institute, Plan-les-Ouates, Switzerland Keywords: Local Replication, Local Score, Association In gene-mapping, replication of initial findings has been put forwards as the approach of choice for filtering false-positives from true signals for underlying loci. In practice, such replications are however too poorly observed. Besides the statistical and technical-related factors (lack of power, multiple-testing, stratification, quality control,) inconsistent conclusions obtained from independent populations might result from real biological differences. In particular, the high degree of variation in the strength of LD among populations of different origins is a major challenge to the discovery of genes. Seeking for Local Replications (defined as the presence of a signal of association in a same genomic region among populations) instead of strict replications (same locus, same risk allele) may lead to more reliable results. Recently, a multi-markers approach based on the Local Score statistic has been proposed as a simple and efficient way to select candidate genomic regions at the first stage of genome-wide association studies. Here we propose an extension of this approach adapted to replicated association studies. Based on simulations, this method appears promising. In particular it outperforms classical simple-marker strategies to detect modest-effect genes. Additionally it constitutes, to our knowledge, a first framework dedicated to the detection of such Local Replications. Juliet Chapman 1 , Claudio Verzilli 1 , John Whittaker 156 Department of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, UK Keywords: FDR, Association studies, Bayesian model selection As genomewide association studies become commonplace there is debate as to how such studies might be analysed and what we might hope to gain from the data. It is clear that standard single locus approaches are limited in that they do not adjust for the effects of other loci and problematic since it is not obvious how to adjust for multiple comparisons. False discovery rates have been suggested, but it is unclear how well these will cope with highly correlated genetic data. We consider the validity of standard false discovery rates in large scale association studies. We also show that a Bayesian procedure has advantages in detecting causal loci amongst a large number of dependant SNPs and investigate properties of a Bayesian FDR. Peter Kraft 157 Harvard School of Public Health, Boston USA Keywords: Gene-environment interaction, genome-wide association scans Appropriately analyzed two-stage designs,where a subset of available subjects are genotyped on a genome-wide panel of markers at the first stage and then a much smaller subset of the most promising markers are genotyped on the remaining subjects,can have nearly as much power as a single-stage study where all subjects are genotyped on the genome-wide panel yet can be much less expensive. Typically, the "most promising" markers are selected based on evidence for a marginal association between genotypes and disease. Subsequently, the few markers found to be associated with disease at the end of the second stage are interrogated for evidence of gene-environment interaction, mainly to understand their impact on disease etiology and public health impact. However, this approach may miss variants which have a sizeable effect restricted to one exposure stratum and therefore only a modest marginal effect. We have proposed to use information on the joint effects of genes and a discrete list of environmental exposures at the initial screening stage to select promising markers for the second stage [Kraft et al Hum Hered 2007]. This approach optimizes power to detect variants that have a sizeable marginal effect and variants that have a small marginal effect but a sizeable effect in a stratum defined by an environmental exposure. As an example, I discuss a proposed genome-wide association scan for Type II diabetes susceptibility variants based in several large nested case-control studies. Beate Glaser 1 , Peter Holmans 158 Biostatistics and Bioinformatics Unit, Cardiff University, School of Medicine, Heath Park, Cardiff, UK Keywords: Combined case-control and trios analysis, Power, False-positive rate, Simulation, Association studies The statistical power of genetic association studies can be enhanced by combining the analysis of case-control with parent-offspring trio samples. Various combined analysis techniques have been recently developed; as yet, there have been no comparisons of their power. This work was performed with the aim of identifying the most powerful method among available combined techniques including test statistics developed by Kazeem and Farrall (2005), Nagelkerke and colleagues (2004) and Dudbridge (2006), as well as a simple combination of ,2-statistics from single samples. Simulation studies were performed to investigate their power under different additive, multiplicative, dominant and recessive disease models. False-positive rates were determined by studying the type I error rates under null models including models with unequal allele frequencies between the single case-control and trios samples. We identified three techniques with equivalent power and false-positive rates, which included modifications of the three main approaches: 1) the unmodified combined Odds ratio estimate by Kazeem & Farrall (2005), 2) a modified approach of the combined risk ratio estimate by Nagelkerke & colleagues (2004) and 3) a modified technique for a combined risk ratio estimate by Dudbridge (2006). Our work highlights the importance of studies investigating test performance criteria of novel methods, as they will help users to select the optimal approach within a range of available analysis techniques. David Almorza 1 , M.V. Kandus 2 , Juan Carlos Salerno 2 , Rafael Boggio 359 Facultad de Ciencias del Trabajo, University of Cádiz, Spain 60 Instituto de Genética IGEAF, Buenos Aires, Argentina 61 Universidad Nacional de La Plata, Buenos Aires, Argentina Keywords: Principal component analysis, maize, ear weight, inbred lines The objective of this work was to evaluate the relationship among different traits of the ear of maize inbred lines and to group genotypes according to its performance. Ten inbred lines developed at IGEAF (INTA Castelar) and five public inbred lines as checks were used. A field trial was carried out in Castelar, Buenos Aires (34° 36' S , 58° 39' W) using a complete randomize design with three replications. At harvest, individual weight (P.E.), diameter (D.E.), row number (N.H.) and length (L.E.) of the ear were assessed. A principal component analysis, PCA, (Infostat 2005) was used, and the variability of the data was depicted with a biplot. Principal components 1 and 2 (CP1 and CP2) explained 90% of the data variability. CP1 was correlated with P.E., L.E. and D.E., meanwhile CP2 was correlated with N.H. We found that individual weight (P.E.) was more correlated with diameter of the ear (D.E.) than with length (L.E). Five groups of inbred lines were distinguished: with high P.E. and mean N.H. (04-70, 04-73, 04-101 and MO17), with high P.E. but less N.H. (04-61 and B14), with mean P.E. and N.H. (B73, 04-123 and 04-96), with high N.H. but less P.E. (LP109, 04-8, 04-91 and 04-76) and with low P.E. and low N.H. (LP521 and 04-104). The use of PCA showed which variables had more incidence in ear weight and how is the correlation among them. Moreover, the different groups found with this analysis allow the evaluation of inbred lines by several traits simultaneously. Sven Knüppel 1 , Anja Bauerfeind 1 , Klaus Rohde 162 Department of Bioinformatics, MDC Berlin, Germany Keywords: Haplotypes, association studies, case-control, nuclear families The area of gene chip technology provides a plethora of phase-unknown SNP genotypes in order to find significant association to some genetic trait. To circumvent possibly low information content of a single SNP one groups successive SNPs and estimates haplotypes. Haplotype estimation, however, may reveal ambiguous haplotype pairs and bias the application of statistical methods. Zaykin et al. (Hum Hered, 53:79-91, 2002) proposed the construction of a design matrix to take this ambiguity into account. Here we present a set of functions written for the Statistical package R, which carries out haplotype estimation on the basis of the EM-algorithm for individuals (case-control) or nuclear families. The construction of a design matrix on basis of estimated haplotypes or haplotype pairs allows application of standard methods for association studies (linear, logistic regression), as well as statistical methods as haplotype sharing statistics and TDT-Test. Applications of these methods to genome-wide association screens will be demonstrated. Manuela Zucknick 1 , Chris Holmes 2 , Sylvia Richardson 163 Department of Epidemiology and Public Health, Imperial College London, UK 64 Department of Statistics, Oxford Center for Gene Function, University of Oxford, UK Keywords: Bayesian, variable selection, MCMC, large p, small n, structured dependence In large-scale genomic applications vast numbers of markers or genes are scanned to find a few candidates which are linked to a particular phenotype. Statistically, this is a variable selection problem in the "large p, small n" situation where many more variables than samples are available. An additional feature is the complex dependence structure which is often observed among the markers/genes due to linkage disequilibrium or their joint involvement in biological processes. Bayesian variable selection methods using indicator variables are well suited to the problem. Binary phenotypes like disease status are common and both Bayesian probit and logistic regression can be applied in this context. We argue that logistic regression models are both easier to tune and to interpret than probit models and implement the approach by Holmes & Held (2006). Because the model space is vast, MCMC methods are used as stochastic search algorithms with the aim to quickly find regions of high posterior probability. In a trade-off between fast-updating but slow-moving single-gene Metropolis-Hastings samplers and computationally expensive full Gibbs sampling, we propose to employ the dependence structure among the genes/markers to help decide which variables to update together. Also, parallel tempering methods are used to aid bold moves and help avoid getting trapped in local optima. Mixing and convergence of the resulting Markov chains are evaluated and compared to standard samplers in both a simulation study and in an application to a gene expression data set. Reference Holmes, C. C. & Held, L. (2006) Bayesian auxiliary variable models for binary and multinomial regression. Bayesian Analysis1, 145,168. Dawn Teare 165 MMGE, University of Sheffield, UK Keywords: CNP, family-based analysis, MCMC Evidence is accumulating that segmental copy number polymorphisms (CNPs) may represent a significant portion of human genetic variation. These highly polymorphic systems require handling as phenotypes rather than co-dominant markers, placing new demands on family-based analyses. We present an integrated approach to meet these challenges in the form of a graphical model, where the underlying discrete CNP phenotype is inferred from the (single or replicate) quantitative measure within the analysis, whilst assuming an allele based system segregating through the pedigree. [source] Cooperation and conflict in host,microbe relationsAPMIS, Issue 5-6 2009ELLING ULVESTAD Hosts and microbes associate in a variety of relations along a continuum ranging from symbiotic to pathogenic. Defence mechanisms have been evolutionarily selected in both hosts and microbes to protect the organism's integrity. Such defences have to be utilized with caution. They must be adapted to the tasks at hand; otherwise any symbiotic relation would be impossible. To explain this cautionary use of defences we need to understand how life on Earth evolved into cooperative and competing entities at various levels of organization. The purpose of this article is to review theory and selected mechanisms relating to the evolution and development of host,microbe interactions, with special emphasis on host responses. The rationale is that without theory, extrapolations from misleading observations can dominate and distort, for a significant time, the course of a scientific field. The argument is set forth that social evolution theory provides a conceptual framework for addressing questions relating to interaction between hosts and microbes. The article is a partial summary of arguments presented in my book Defending life , the nature of host,parasite relations. [source] ChemInform Abstract: Ln2(OH)5NO3×xH2O (Ln: Y, Gd,Lu): A Novel Family of Anion Exchange Intercalation Hosts.CHEMINFORM, Issue 15 2008Laura J. McIntyre Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Supramolecular Chirogenesis with Bis-Chlorin versus Bis-Porphyrin Hosts: Peculiarities of Chirality Induction and Modulation of Optical Activity.CHEMINFORM, Issue 3 2006Victor V. Borovkov No abstract is available for this article. [source] ChemInform Abstract: Formation of Metal,Anion Arrays within Layered Perovskite Hosts.CHEMINFORM, Issue 37 2002(MCl)LaNb2O7 (M: Cr, Preparation of a Series of New Metastable Transition-Metal Oxyhalides Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Contributions of Lipid Bilayer Hosts to Structure and Activity of Multifunctional Supramolecular GuestsCHEMISTRY & BIODIVERSITY, Issue 6 2005Abhigyan Som The question of whether or not the surrounding lipid bilayer host contributes to structure and activity of included functional guests is a general topic of current scientific concern. We report that synthetic multifunctional pores are of use to address this elusive question, because the detection of their catalytic activity is membrane independent. According to their salt-rate profiles, unstable multifunctional supramolecules with permanent internal charges show highest membrane sensitivity, and the dependence of membrane sensitivity on the acidity of internal cations exceeds that on supramolecule stability. These results can, with all appropriate caution, be interpreted as indications for the existence of long-range EMP,ICR interactions (EMP: external membrane pressure, ICR: internal charge repulsion) between membrane hosts and functional guests that can, for instance, prevent the ,explosion' and promote the ,implosion' of over- and undercharged transmembrane barrel-stave supramolecules, respectively. [source] Distributed end-host multicast algorithms for the Knowledge GridCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 15 2007Wanqing Tu Abstract The Knowledge Grid built on top of the peer-to-peer (P2P) network has been studied to implement scalable, available and sematic-based querying. In order to improve the efficiency and scalability of querying, this paper studies the problem of multicasting queries in the Knowledge Grid. An m -dimensional irregular mesh is a popular overlay topology of P2P networks. We present a set of novel distributed algorithms on top of an m -dimensional irregular mesh overlay for the short delay and low network resource consumption end-host multicast services. Our end-host multicast fully utilizes the advantages of an m -dimensional mesh to construct a two-layer architecture. Compared to previous approaches, the novelty and contribution here are: (1) cluster formation that partitions the group members into clusters in the lower layer where cluster consists of a small number of members; (2) cluster core selection that searches a core with the minimum sum of overlay hops to all other cluster members for each cluster; (3) weighted shortest path tree construction that guarantees the minimum number of shortest paths to be occupied by the multicast traffic; (4) distributed multicast routing that directs the multicast messages to be efficiently distributed along the two-layer multicast architecture in parallel, without a global control; the routing scheme enables the packets to be transmitted to the remote end hosts within short delays through some common shortest paths; and (5) multicast path maintenance that restores the normal communication once the membership alteration appears. Simulation results show that our end-host multicast can distributively achieve a shorter delay and lower network resource consumption multicast services as compared with some well-known end-host multicast systems. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||