Sample records for quantitative phenotypic variation

  1. Quantitative variation and phenotypic correlations in banana and plantain

    Microsoft Academic Search

    Rodomiro Ortiz; Dirk Vuylsteke

    1998-01-01

    Plantains exhibit great variability in West and Central Africa, which accounts for 60% of world production. Sixteen quantitative characteristics were evaluated in 75 plantain and 18 banana cultivars during several production cycles. The extent of variation in quantitative continuous characteristics and the phenotypic correlations between them were analysed. Index descriptors based on the combination of two characteristics were calculated. Despite

  2. Beyond Punnett Squares: Student Word Association and Explanations of Phenotypic Variation through an Integrative Quantitative Genetics Unit Investigating Anthocyanin Inheritance and Expression in "Brassica rapa" Fast Plants

    ERIC Educational Resources Information Center

    Batzli, Janet M.; Smith, Amber R.; Williams, Paul H.; McGee, Seth A.; Dosa, Katalin; Pfammatter, Jesse

    2014-01-01

    Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question "What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev)," we developed a 4-wk unit for an inquiry-based laboratory…

  3. Beyond Punnett squares: Student word association and explanations of phenotypic variation through an integrative quantitative genetics unit investigating anthocyanin inheritance and expression in Brassica rapa Fast plants.

    PubMed

    Batzli, Janet M; Smith, Amber R; Williams, Paul H; McGee, Seth A; Dósa, Katalin; Pfammatter, Jesse

    2014-01-01

    Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question "What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev)," we developed a 4-wk unit for an inquiry-based laboratory course focused on the inheritance and expression of a quantitative trait in varying environments. We utilized Brassica rapa Fast Plants as a model organism to study variation in the phenotype anthocyanin pigment intensity. As an initial curriculum assessment, we used free word association to examine students' cognitive structures before and after the unit and explanations in students' final research posters with particular focus on variation (Pv = Gv + Ev). Comparison of pre- and postunit word frequency revealed a shift in words and a pattern of co-occurring concepts indicative of change in cognitive structure, with particular focus on "variation" as a proposed threshold concept and primary goal for students' explanations. Given review of 53 posters, we found ?50% of students capable of intermediate to high-level explanations combining both Gv and Ev influence on expression of anthocyanin intensity (Pv). While far from "plug and play," this conceptually rich, inquiry-based unit holds promise for effective integration of quantitative and Mendelian genetics. PMID:25185225

  4. Interpreting phenotypic variation in plants

    NSDL National Science Digital Library

    This article by Coleman, McConnaughay, and Ackerly discusses how phenotypic variation (variation in observable traits) in plants is influenced by environment, genetics, and developmental stage. The authors stress that understanding the interplay of these factors is important for investigations that involve plant comparisons.

  5. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects

    Microsoft Academic Search

    Ron Korstanje; Jigar Desai; Gloria Lazar; Benjamin King; Jarod Rollins; Melissa Spurr; Jamie Joseph; Sindhuja Kadambi; Yang Li; Allison Cherry; Paul G. Matteson; Beverly Paigen; James H. Millonig

    2008-01-01

    The vacuolated lens (vl) mouse mutant arose spontaneously on the C3H\\/HeSn background and exhibits neural tube defects (NTDs), congenital cataract, and occasionally a white belly spot. We previously reported that 1) the vl phenotypes are due to a mutation in an orphan G protein-coupled receptor (GPCR), Gpr161; 2) the penetrance of the vl NTD and cataract phenotypes are affected by

  6. Candidate quantitative trait loci and naturally occurring phenotypic variation for bristle number in Drosophila melanogaster: the Delta-Hairless gene region.

    PubMed

    Lyman, R F; Mackay, T F

    1998-06-01

    Delta (Dl) and Hairless (H) are two chromosome 3 candidate neurogenic loci that might contribute to naturally occurring quantitative variation for sensory bristle number. To evaluate this hypothesis, we assessed quantitative genetic variation in abdominal and sternopleural bristle numbers among homozygous isogenic third chromosomes sampled from nature and substituted into the Samarkand (Sam) inbred chromosome 1 and 2 background; among homozygous lines in which the wild-derived Dl-H gene region was introgressed into the Sam chromosome 3 background; and among Dl-H region introgression lines as heterozygotes against the Sam wild-type strain and derivatives of Sam into which mutant Dl and H alleles had been introgressed. Variation among the Dl-H region introgression lines accounted for 36% (8.3%) of the total chromosome 3 among line variance in abdominal (sternopleural) bristle number and for 53% of the chromosome 3 sex x line variance in abdominal bristle number. Naturally occurring alleles in the Dl-H region failed to complement a Dl mutant allele for female abdominal bristle number and sternopleural bristle number in both sexes, and an H mutant allele for both bristle traits in males and females. These results are consistent with the hypothesis that naturally occurring alleles at Dl and H contribute to quantitative genetic variation in sensory bristle number. PMID:9611208

  7. Identical mutations and phenotypic variation

    Microsoft Academic Search

    Ulrich Wolf

    1997-01-01

    The relationship between pathogenetic mutations and disease phenotype is becoming increasingly complex. Well-delineated clinical\\u000a entities can be genetically heterogeneous, and mutations in a particular gene may result in fundamental clinical differences.\\u000a Genetic heterogeneity includes mutations at different gene loci or allelic mutations within a single gene, resulting in a\\u000a similar phenotype. However, one and the same mutation is expected to

  8. Effect of genotype × alcoholism interaction on linkage analysis of an alcoholism-related quantitative phenotype

    Microsoft Academic Search

    Rector Arya; Thomas D Dyer; Diane M Warren; Christopher P Jenkinson; Ravindranath Duggirala; Laura Almasy

    2005-01-01

    Studies have shown that genetic and environmental factors and their interactions affect several alcoholism phenotypes. Genotype × alcoholism (G×A) interaction refers to the environmental (alcoholic and non-alcoholic) influences on the autosomal genes contributing to variation in an alcoholism-related quantitative phenotype. The purpose of this study was to examine the effects of G×A interaction on the detection of linkage for alcoholism-related

  9. Environmental stress and quantitative genetic variation in butterfly wing characteristics

    Microsoft Academic Search

    W. Talloen; S. Van Dongen; H. Van Dyck; L. Lens

    2009-01-01

    Butterfly wing characteristics are extensively used as model system in studies of development, quantitative genetics and phenotypic\\u000a plasticity. In spite of its evolutionary relevance, however, the effect of stress on the expression of genetic variation itself\\u000a has only rarely been studied. In this paper, we explore genetic variation of wing characteristics of the Speckled wood Pararge aegeria along a host

  10. Quantitative biometric phenotype analysis in mouse lenses

    PubMed Central

    Reilly, Matthew A.

    2010-01-01

    The disrupted morphology of lenses in mouse models for cataracts precludes accurate in vitro assessment of lens growth by weight. To overcome this limitation, we developed morphometric methods to assess defects in eye lens growth and shape in mice expressing the ?A-crystallin R49C (?A-R49C) mutation. Our morphometric methods determine quantitative shape and dry weight of the whole lens from histological sections of the lens. This method was then used to quantitatively compare the biometric growth patterns of lenses of different genotypes of mice from birth to 12 months. The wild type dry lens weights determined using the morphometric method were comparable to previously reported weights. Next we applied the method to assessing the lenses of ?A-R49C knock-in mice, which exhibit decreased ?A-crystallin protein solubility, resulting in a variety of growth abnormalities including early cataract formation, decreased eye and lens size, failure to form the equatorial bow region, and continued lens cell death, sometimes resulting in the entire loss of the lens and eye. Our morphometric methods reproducibly quantified these defects by combining histology, microscopy, and image analysis. The volume measurement accurately represented the total growth of the lens, whereas the geometric shape of the lens more accurately quantified the differences between the growth of the mutant and wild-type lenses. These methods are robust tools for measuring dry lens weight and quantitatively comparing the growth of small lenses that are difficult to weigh accurately such as those from very young mice and mice with developmental lens defects. PMID:20606707

  11. Linking post-translational modifications and variation of phenotypic traits.

    PubMed

    Albertin, Warren; Marullo, Philippe; Bely, Marina; Aigle, Michel; Bourgais, Aurélie; Langella, Olivier; Balliau, Thierry; Chevret, Didier; Valot, Benoît; da Silva, Telma; Dillmann, Christine; de Vienne, Dominique; Sicard, Delphine

    2013-03-01

    Enzymes can be post-translationally modified, leading to isoforms with different properties. The phenotypic consequences of the quantitative variability of isoforms have never been studied. We used quantitative proteomics to dissect the relationships between the abundances of the enzymes and isoforms of alcoholic fermentation, metabolic traits, and growth-related traits in Saccharomyces cerevisiae. Although the enzymatic pool allocated to the fermentation proteome was constant over the culture media and the strains considered, there was variation in abundance of individual enzymes and sometimes much more of their isoforms, which suggests the existence of selective constraints on total protein abundance and trade-offs between isoforms. Variations in abundance of some isoforms were significantly associated to metabolic traits and growth-related traits. In particular, cell size and maximum population size were highly correlated to the degree of N-terminal acetylation of the alcohol dehydrogenase. The fermentation proteome was found to be shaped by human selection, through the differential targeting of a few isoforms for each food-processing origin of strains. These results highlight the importance of post-translational modifications in the diversity of metabolic and life-history traits. PMID:23271801

  12. Global Climate Change and Phenotypic Variation among Red Deer Cohorts

    Microsoft Academic Search

    Eric Post; Nils Chr. Stenseth; Rolf Langvatn; Jean-Marc Fromentin

    1997-01-01

    The variability of two fitness-related phenotypic traits (body weight and a mandibular skeletal ratio) was analysed among cohorts and age-classes of red deer in Norway. Phenotypic variation among cohorts was pronounced for calves, yearlings and reproductively mature adults. Fluctuations in cohort-specific mean body weights and skeletal ratios of adults correlated with global climatic variation in winter conditions influenced by the

  13. Drosophila bristles and the nature of quantitative genetic variation

    PubMed Central

    Mackay, Trudy F.C; Lyman, Richard F

    2005-01-01

    Numbers of Drosophila sensory bristles present an ideal model system to elucidate the genetic basis of variation for quantitative traits. Here, we review recent evidence that the genetic architecture of variation for bristle numbers is surprisingly complex. A substantial fraction of the Drosophila genome affects bristle number, indicating pervasive pleiotropy of genes that affect quantitative traits. Further, a large number of loci, often with sex- and environment-specific effects that are also conditional on background genotype, affect natural variation in bristle number. Despite this complexity, an understanding of the molecular basis of natural variation in bristle number is emerging from linkage disequilibrium mapping studies of individual candidate genes that affect the development of sensory bristles. We show that there is naturally segregating genetic variance for environmental plasticity of abdominal and sternopleural bristle number. For abdominal bristle number this variance can be attributed in part to an abnormal abdomen-like phenotype that resembles the phenotype of mutants defective in catecholamine biosynthesis. Dopa decarboxylase (Ddc) encodes the enzyme that catalyses the final step in the synthesis of dopamine, a major Drosophila catecholamine and neurotransmitter. We found that molecular polymorphisms at Ddc are indeed associated with variation in environmental plasticity of abdominal bristle number. PMID:16108138

  14. Multifactorial geneticsUnderstanding quantitative genetic variation

    Microsoft Academic Search

    Peter D. Keightley; Nicholas H. Barton

    2001-01-01

    Until recently, it was impracticable to identify the genes that are responsible for variation in continuous traits, or to directly observe the effects of their different alleles. Now, the abundance of genetic markers has made it possible to identify quantitative trait loci (QTL) — the regions of a chromosome or, ideally, individual sequence variants that are responsible for trait variation.

  15. Computerized image analysis for quantitative neuronal phenotyping in zebrafish.

    PubMed

    Liu, Tianming; Lu, Jianfeng; Wang, Ye; Campbell, William A; Huang, Ling; Zhu, Jinmin; Xia, Weiming; Wong, Stephen T C

    2006-06-15

    An integrated microscope image analysis pipeline is developed for automatic analysis and quantification of phenotypes in zebrafish with altered expression of Alzheimer's disease (AD)-linked genes. We hypothesize that a slight impairment of neuronal integrity in a large number of zebrafish carrying the mutant genotype can be detected through the computerized image analysis method. Key functionalities of our zebrafish image processing pipeline include quantification of neuron loss in zebrafish embryos due to knockdown of AD-linked genes, automatic detection of defective somites, and quantitative measurement of gene expression levels in zebrafish with altered expression of AD-linked genes or treatment with a chemical compound. These quantitative measurements enable the archival of analyzed results and relevant meta-data. The structured database is organized for statistical analysis and data modeling to better understand neuronal integrity and phenotypic changes of zebrafish under different perturbations. Our results show that the computerized analysis is comparable to manual counting with equivalent accuracy and improved efficacy and consistency. Development of such an automated data analysis pipeline represents a significant step forward to achieve accurate and reproducible quantification of neuronal phenotypes in large scale or high-throughput zebrafish imaging studies. PMID:16364449

  16. Environmental Effects on the Expression of Quantitative Trait Loci and Implications for Phenotypic Evolution

    NSDL National Science Digital Library

    CYNTHIA WEINIG and JOHANNA SCHMITT (; )

    2004-07-01

    This peer-reviewed resource from Bioscience magazine is about the use of mapping quantitative trait loci in evolutionary studies. Organisms in natural populations experience environmental heterogeneity over a range of temporal and spatial scales, and this heterogeneity has significant evolutionary implications. By affecting patterns of selection and the expression of genetic variation, environmental heterogeneity can play an important role in determining the evolutionary dynamics of phenotypic traits and the maintenance of genetic variation. Although mapping quantitative trait loci (the loci that underlie continuously varying quantitative traits) has a long history in agricultural and applied studies, the technique has only recently been applied to evolutionary studies. This application has made it possible to identify the specific loci underlying trait variation in different environments, to measure environmental variation in natural selection on those loci, and to test assumptions of models regarding the maintenance of genetic variation under environmentally heterogeneous selection. Here we review recent studies that have examined interactions between quantitative trait loci and ecologically relevant environments to address evolutionary questions.

  17. High Phenotypic and Molecular Variation in Downy Brome (Bromus tectorum)

    E-print Network

    Hufbauer, Ruth A.

    High Phenotypic and Molecular Variation in Downy Brome (Bromus tectorum) Rebecca H. Kao, Cynthia S. Brown, and Ruth A. Hufbauer* The invasive grass Bromus tectorum (cheatgrass, downy brome) has extensive, especially into new habitats. Nomenclature: Downy brome, Bromus tectorum L. BROTE. Key words: Broad

  18. The role of phenotypic variation in rhizosphere Pseudomonas bacteria.

    PubMed

    van den Broek, Daan; Bloemberg, Guido V; Lugtenberg, Ben

    2005-11-01

    Colony phase variation is a regulatory mechanism at the DNA level which usually results in high frequency, reversible switches between colonies with a different phenotype. A number of molecular mechanisms underlying phase variation are known: slipped-strand mispairing, genomic rearrangements, spontaneous mutations and epigenetic mechanisms such as differential methylation. Most examples of phenotypic variation or phase variation have been described in the context of host-pathogen interactions as mechanisms allowing pathogens to evade host immune responses. Recent reports indicate that phase variation is also relevant in competitive root colonization and biological control of phytopathogens. Many rhizospere Pseudomonas species show phenotypic variation, based on spontaneous mutation of the gacA and gacS genes. These morphological variants do not express secondary metabolites and have improved growth characteristics. The latter could contribute to efficient root colonization and success in competition, especially since (as shown for one strain) these variants were observed to revert to their wild-type form. The observation that these variants are present in rhizosphere-competent Pseudomonas bacteria suggests the existence of a conserved strategy to increase their success in the rhizosphere. PMID:16232284

  19. A Penalized Mixture Model Approach in Genotype/Phenotype Association Analysis for Quantitative Phenotypes

    PubMed Central

    Li, Lang; Borges, Silvana; Jason, Robarge D.; Shen, Changyu; Desta, Zeruesenay; Flockhart, David

    2010-01-01

    A mixture normal model has been developed to partition genotypes in predicting quantitative phenotypes. Its estimation and inference are performed through an EM algorithm. This approach can conduct simultaneous genotype clustering and hypothesis testing. It is a valuable method for predicting the distribution of quantitative phenotypes among multi-locus genotypes across genes or within a gene. This mixture model’s performance is evaluated in data analyses for two pharmacogenetics studies. In one example, thirty five CYP2D6 genotypes were partitioned into three groups to predict pharmacokinetics of a breast cancer drug, Tamoxifen, a CYP2D6 substrate (p-value = 0.04). In a second example, seventeen CYP2B6 genotypes were categorized into three clusters to predict CYP2B6 protein expression (p-value = 0.002). The biological validities of both partitions are examined using established function of CYP2D6 and CYP2B6 alleles. In both examples, we observed genotypes clustered in the same group to have high functional similarities. The power and recovery rate of the true partition for the mixture model approach are investigated in statistical simulation studies, where it outperforms another published method. PMID:20467479

  20. Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

    PubMed Central

    Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

    2008-01-01

    Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

  1. Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes

    PubMed Central

    Carless, M.A.; Glahn, D.C.; Johnson, M.P.; Curran, J.E.; Bozaoglu, K.; Dyer, T.D.; Winkler, A.M.; Cole, S.A.; Almasy, L.; MacCluer, J.W.; Duggirala, R.; Moses, E.K.; Göring, H.H.H.; Blangero, J.

    2011-01-01

    Although DISC1 has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted transcriptional profiling and genome-wide association analysis in 1 232 pedigreed Mexican American individuals for whom we have neuroanatomic images, neurocognitive assessments and neuropsychiatric diagnoses. SOLAR was used to determine heritability, identify gene expression patterns and perform association analyses on 188 quantitative brain-related phenotypes. We found that the DISC1 transcript is highly heritable (h2=0.50; p=1.97 × 10?22), and that gene expression is strongly cis-regulated (cis-LOD=3.89) but is also influenced by trans-effects. We identified several DISC1 polymorphisms that were associated with cortical gray-matter thickness within the parietal, temporal and frontal lobes. Associated regions affiliated with memory included the entorhinal cortex (rs821639, p=4.11 × 10?5; rs2356606, p=4.71 × 10?4), cingulate cortex (rs16856322, p=2.88 × 10?4) and parahippocampal gyrus (rs821639, p=4.95 × 10?4); those affiliated with executive and other cognitive processing included the transverse temporal gyrus (rs9661837, p=5.21 × 10?4; rs17773946, p=6.23 × 10?4), anterior cingulate cortex (rs2487453, p=; 4.79 × 10?4; rs3738401, p= 5.43 × 10?4) and medial orbitofrontal cortex (rs9661837; p=7.40 × 10?4). Cognitive measures of working memory (rs2793094, p=3.38 × 10?4), as well as lifetime history of depression (rs4658966, p=4.33 × 10?4; rs12137417, p=4.93 × 10?4) and panic (rs12137417, p=7.41 × 10?4) were associated with DISC1 sequence variation. DISC1 has well-defined genetic regulation and clearly influences important phenotypes related to psychiatric disease. PMID:21483430

  2. Effect of genotype x alcoholism interaction on linkage analysis of an alcoholism-related quantitative phenotype.

    PubMed

    Arya, Rector; Dyer, Thomas D; Warren, Diane M; Jenkinson, Christopher P; Duggirala, Ravindranath; Almasy, Laura

    2005-01-01

    Studies have shown that genetic and environmental factors and their interactions affect several alcoholism phenotypes. Genotype x alcoholism (GxA) interaction refers to the environmental (alcoholic and non-alcoholic) influences on the autosomal genes contributing to variation in an alcoholism-related quantitative phenotype. The purpose of this study was to examine the effects of GxA interaction on the detection of linkage for alcoholism-related phenotypes. We used phenotypic and genotypic data from the Collaborative Study on the Genetics of Alcoholism relating to 1,388 subjects as part of Genetic Analysis Workshop 14 problem 1. We analyzed the MXDRNK phenotype to detect GxA interaction using SOLAR. Upon detecting significant interaction, we conducted variance-component linkage analyses using microsatellite marker data. For maximum number of drinks per a 24 hour period, the highest LODs were observed on chromosomes 1, 4, and 13 without GxA interaction. Interaction analysis yielded four regions on chromosomes 1, 4, 13, and 15. On chromosome 4, a maximum LOD of 1.5 at the same location as the initial analysis was obtained after incorporating GxA interaction effects. However, after correcting for extra parameters, the LOD score was reduced to a corrected LOD of 1.1, which is similar to the LOD observed in the non-interaction analysis. Thus, we see little differences in LOD scores, while some linkage regions showed large differences in the magnitudes of estimated quantitative trait loci heritabilities between the alcoholic and non-alcoholic groups. These potential hints of differences in genetic effect may influence future analyses of variants under these linkage peaks. PMID:16451578

  3. The Evolution of Human Genetic and Phenotypic Variation in Africa

    PubMed Central

    Campbell, Michael C.

    2010-01-01

    Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations. PMID:20178763

  4. The relationship between parental genetic or phenotypic divergence and progeny variation in the maize nested association mapping population

    PubMed Central

    Hung, H-Y; Browne, C; Guill, K; Coles, N; Eller, M; Garcia, A; Lepak, N; Melia-Hancock, S; Oropeza-Rosas, M; Salvo, S; Upadyayula, N; Buckler, E S; Flint-Garcia, S; McMullen, M D; Rocheford, T R; Holland, J B

    2012-01-01

    Appropriate selection of parents for the development of mapping populations is pivotal to maximizing the power of quantitative trait loci detection. Trait genotypic variation within a family is indicative of the family's informativeness for genetic studies. Accurate prediction of the most useful parental combinations within a species would help guide quantitative genetics studies. We tested the reliability of genotypic and phenotypic distance estimators between pairs of maize inbred lines to predict genotypic variation for quantitative traits within families derived from biparental crosses. We developed 25 families composed of ?200 random recombinant inbred lines each from crosses between a common reference parent inbred, B73, and 25 diverse maize inbreds. Parents and families were evaluated for 19 quantitative traits across up to 11 environments. Genetic distances (GDs) among parents were estimated with 44 simple sequence repeat and 2303 single-nucleotide polymorphism markers. GDs among parents had no predictive value for progeny variation, which is most likely due to the choice of neutral markers. In contrast, we observed for about half of the traits measured a positive correlation between phenotypic parental distances and within-family genetic variance estimates. Consequently, the choice of promising segregating populations can be based on selecting phenotypically diverse parents. These results are congruent with models of genetic architecture that posit numerous genes affecting quantitative traits, each segregating for allelic series, with dispersal of allelic effects across diverse genetic material. This architecture, common to many quantitative traits in maize, limits the predictive value of parental genotypic or phenotypic values on progeny variance. PMID:22027895

  5. Intraspecific phenotypic variation among alewife populations drives parallel phenotypic shifts in bluegill.

    PubMed

    Huss, Magnus; Howeth, Jennifer G; Osterman, Julia I; Post, David M

    2014-07-22

    Evolutionary diversification within consumer species may generate selection on local ecological communities, affecting prey community structure. However, the extent to which this niche construction can propagate across food webs and shape trait variation in competing species is unknown. Here, we tested whether niche construction by different life-history variants of the planktivorous fish alewife (Alosa pseudoharengus) can drive phenotypic divergence and resource use in the competing species bluegill (Lepomis macrochirus). Using a combination of common garden experiments and a comparative field study, we found that bluegill from landlocked alewife lakes grew relatively better when fed small than large zooplankton, had gill rakers better adapted for feeding on small-bodied prey and selected smaller zooplankton compared with bluegill from lakes with anadromous or no alewife. Observed shifts in bluegill foraging traits in lakes with landlocked alewife parallel those in alewife, suggesting interspecific competition leading to parallel phenotypic changes rather than to divergence (which is commonly predicted). Our findings suggest that species may be locally adapted to prey communities structured by different life-history variants of a competing dominant species. PMID:24920478

  6. Quantitative Classification and Natural Clustering of C. elegans Behavioral Phenotypes

    E-print Network

    Cosman, Pamela C.

    Learning; Phenotypic analysis #12;2 ABSTRACT Genetic analysis of nervous system function relies the behavioral patterns of C. elegans nervous system mutants. We have used an automated tracking and image. elegans has a simple nervous system consisting of 302 neurons of known position, cell lineage

  7. Maintenance of quantitative genetic variation in animal breeding programmes

    Microsoft Academic Search

    William G Hill

    2000-01-01

    Factors influencing the maintenance of genetic variation in quantitative traits in populations undergoing artificial selection are reviewed. Formulae are given for simple cases, in particular for the infinitesimal model where variation is lost by genetic drift and gained by mutation and therefore the minimum population size to maintain genetic variation is a function of mutation rate. For genes with effects

  8. Disentangling the phylogenetic and ecological components of spider phenotypic variation.

    PubMed

    Gonçalves-Souza, Thiago; Diniz-Filho, José Alexandre Felizola; Romero, Gustavo Quevedo

    2014-01-01

    An understanding of how the degree of phylogenetic relatedness influences the ecological similarity among species is crucial to inferring the mechanisms governing the assembly of communities. We evaluated the relative importance of spider phylogenetic relationships and ecological niche (plant morphological variables) to the variation in spider body size and shape by comparing spiders at different scales: (i) between bromeliads and dicot plants (i.e., habitat scale) and (ii) among bromeliads with distinct architectural features (i.e., microhabitat scale). We partitioned the interspecific variation in body size and shape into phylogenetic (that express trait values as expected by phylogenetic relationships among species) and ecological components (that express trait values independent of phylogenetic relationships). At the habitat scale, bromeliad spiders were larger and flatter than spiders associated with the surrounding dicots. At this scale, plant morphology sorted out close related spiders. Our results showed that spider flatness is phylogenetically clustered at the habitat scale, whereas it is phylogenetically overdispersed at the microhabitat scale, although phylogenic signal is present in both scales. Taken together, these results suggest that whereas at the habitat scale selective colonization affect spider body size and shape, at fine scales both selective colonization and adaptive evolution determine spider body shape. By partitioning the phylogenetic and ecological components of phenotypic variation, we were able to disentangle the evolutionary history of distinct spider traits and show that plant architecture plays a role in the evolution of spider body size and shape. We also discussed the relevance in considering multiple scales when studying phylogenetic community structure. PMID:24651264

  9. Phenotypic variation of erythrocyte linker histone H1.c in a pheasant (Phasianus colchicus L.) population.

    PubMed

    Kowalski, Andrzej; Pa Yga, Jan; Górnicka-Michalska, Ewa; Bernacki, Zenon; Adamski, Marek

    2010-07-01

    Our goal was to characterize a phenotypic variation of the pheasant erythrocyte linker histone subtype H1.c. By using two-dimensional polyacrylamide gel electrophoresis three histone H1.c phenotypes were identified. The differently migrating allelic variants H1.c1 and H1.c2 formed either two homozygous phenotypes, c1 and c2, or a single heterozygous phenotype, c1c2. In the pheasant population screened, birds with phenotype c2 were the most common (frequency 0.761) while individuals with phenotype c1 were rare (frequency 0.043). PMID:21637419

  10. Population Structure in Daphnia Obtusa: Quantitative Genetic and Allozymic Variation

    PubMed Central

    Spitze, K.

    1993-01-01

    Quantitative genetic analyses for body size and for life history characters within and among populations of Daphnia obtusa reveal substantial genetic variance at both hierarchical levels for all traits measured. Simultaneous allozymic analysis on the same population samples indicate a moderate degree of differentiation: G(ST) = 0.28. No associations between electrophoretic genotype and phenotypic characters were found, providing support for the null hypothesis that the allozymic variants are effectively neutral. Therefore, G(ST) can be used as the null hypothesis that neutral phenotypic evolution within populations led to the observed differentiation for the quantitative traits, which I call Q(ST). The results of this study provide evidence that natural selection has promoted diversification for body size among populations, and has impeded diversification for relative fitness. Analyses of population differentiation for clutch size, age at reproduction, and growth rate indicate that neutral phenotypic evolution cannot be excluded as the cause. PMID:8244001

  11. Consequences of intraspecific niche variation: phenotypic similarity increases competition among recently metamorphosed frogs

    Microsoft Academic Search

    Michael F. Benard; Jessica Middlemis Maher

    2011-01-01

    Phenotype is often correlated with resource use, which suggests that as phenotypic variation in a population increases, intraspecific\\u000a competition will decrease. However, few studies have experimentally tested the prediction that increased intraspecific phenotypic\\u000a variation leads to reduced competitive effects (e.g., on growth rate, survival or reproductive rate). We investigated this\\u000a prediction with two experiments on wood frogs (Rana sylvatica). In

  12. Quantitative phenotypic and pathway profiling guides rational drug combination strategies

    PubMed Central

    Dawson, John C.; Carragher, Neil O.

    2014-01-01

    Advances in target-based drug discovery strategies have enabled drug discovery groups in academia and industry to become very effective at generating molecules that are potent and selective against single targets. However, it has become apparent from disappointing results in recent clinical trials that a major challenge to the development of successful targeted therapies for treating complex multifactorial diseases is overcoming heterogeneity in target mechanism among patients and inherent or acquired drug resistance. Consequently, reductionist target directed drug-discovery approaches are not appropriately tailored toward identifying and optimizing multi-targeted therapeutics or rational drug combinations for complex disease. In this article, we describe the application of emerging high-content phenotypic profiling and analysis tools to support robust evaluation of drug combination performance following dose-ratio matrix screening. We further describe how the incorporation of high-throughput reverse phase protein microarrays with phenotypic screening can provide rational drug combination hypotheses but also confirm the mechanism-of-action of novel drug combinations, to facilitate future preclinical and clinical development strategies. PMID:24904421

  13. Small- and Large-Effect Quantitative Trait Locus Interactions Underlie Variation in Yeast Sporulation Efficiency

    PubMed Central

    Lorenz, Kim; Cohen, Barak A.

    2012-01-01

    Quantitative trait loci (QTL) with small effects on phenotypic variation can be difficult to detect and analyze. Because of this a large fraction of the genetic architecture of many complex traits is not well understood. Here we use sporulation efficiency in Saccharomyces cerevisiae as a model complex trait to identify and study small-effect QTL. In crosses where the large-effect quantitative trait nucleotides (QTN) have been genetically fixed we identify small-effect QTL that explain approximately half of the remaining variation not explained by the major effects. We find that small-effect QTL are often physically linked to large-effect QTL and that there are extensive genetic interactions between small- and large-effect QTL. A more complete understanding of quantitative traits will require a better understanding of the numbers, effect sizes, and genetic interactions of small-effect QTL. PMID:22942125

  14. Adrenocortical responses in zebra finches ( Taeniopygia guttata): Individual variation, repeatability, and relationship to phenotypic quality

    Microsoft Academic Search

    Haruka Wada; Katrina G. Salvante; Christine Stables; Emily Wagner; Tony D. Williams; Creagh W. Breuner

    2008-01-01

    Although individual variation is a key requirement for natural selection, little is known about the magnitude and patterns of individual variation in endocrine systems or the functional significance of that variation. Here we describe (1) the extent and repeatability of inter-individual variation in adrenocortical responses and (2) its relationship to sex-specific phenotypic quality, such as song duration and frequency and

  15. High throughput quantitative phenotyping of plant resistance using chlorophyll fluorescence image analysis

    PubMed Central

    2013-01-01

    Background In order to select for quantitative plant resistance to pathogens, high throughput approaches that can precisely quantify disease severity are needed. Automation and use of calibrated image analysis should provide more accurate, objective and faster analyses than visual assessments. In contrast to conventional visible imaging, chlorophyll fluorescence imaging is not sensitive to environmental light variations and provides single-channel images prone to a segmentation analysis by simple thresholding approaches. Among the various parameters used in chlorophyll fluorescence imaging, the maximum quantum yield of photosystem II photochemistry (Fv/Fm) is well adapted to phenotyping disease severity. Fv/Fm is an indicator of plant stress that displays a robust contrast between infected and healthy tissues. In the present paper, we aimed at the segmentation of Fv/Fm images to quantify disease severity. Results Based on the Fv/Fm values of each pixel of the image, a thresholding approach was developed to delimit diseased areas. A first step consisted in setting up thresholds to reproduce visual observations by trained raters of symptoms caused by Xanthomonas fuscans subsp. fuscans (Xff) CFBP4834-R on Phaseolus vulgaris cv. Flavert. In order to develop a thresholding approach valuable on any cultivars or species, a second step was based on modeling pixel-wise Fv/Fm-distributions as mixtures of Gaussian distributions. Such a modeling may discriminate various stages of the symptom development but over-weights artifacts that can occur on mock-inoculated samples. Therefore, we developed a thresholding approach based on the probability of misclassification of a healthy pixel. Then, a clustering step is performed on the diseased areas to discriminate between various stages of alteration of plant tissues. Notably, the use of chlorophyll fluorescence imaging could detect pre-symptomatic area. The interest of this image analysis procedure for assessing the levels of quantitative resistance is illustrated with the quantitation of disease severity on five commercial varieties of bean inoculated with Xff CFBP4834-R. Conclusions In this paper, we describe an image analysis procedure for quantifying the leaf area impacted by the pathogen. In a perspective of high throughput phenotyping, the procedure was automated with the software R downloadable at http://www.r-project.org/. The R script is available at http://lisa.univ-angers.fr/PHENOTIC/telechargements.html. PMID:23758798

  16. Quantitative Variation, Selection and Inheritance with Fast Plants

    NSDL National Science Digital Library

    The Wisconsin Fast Plants Program

    This article describes how Fast Plants can be used to help students understand how, through genetic selection associated with phenotypic variation, traits are passed on to future generations. This resource includes information about how to analyze variation in a population and selectively breed to change the frequency of a particular trait in future generations. Advanced Placement teachers who are teaching AP Inquiry Investigation #1, Artificial Selection, will find this article relevant to that inquiry.

  17. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome

    E-print Network

    Broman, Karl W.

    Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome and premature mortality. Fundamental to this association, commonly referred to as the metabolic syndrome with a series of related metabolic variables, termed ``syndrome X,'' which cluster in the same individual

  18. Resource variation and the evolution of phenotypic plasticity in fishes 

    E-print Network

    Ruehl, Clifton Benjamin

    2004-09-30

    Resource variation and species interactions require organisms to respond behaviorally, physiologically, and morphologically within and among generations to compensate for spatial and temporal environmental variation. One successful evolutionary...

  19. Geographical Variation in a Quantitative Character

    PubMed Central

    Nagylaki, T.

    1994-01-01

    A model for the evolution of the local averages of a quantitative character under migration, selection, and random genetic drift in a subdivided population is formulated and investigated. Generations are discrete and nonoverlapping; the monoecious, diploid population mates at random in each deme. All three evolutionary forces are weak, but the migration pattern and the local population numbers are otherwise arbitrary. The character is determined by purely additive gene action and a stochastically independent environment; its distribution is Gaussian with a constant variance; and it is under Gaussian stabilizing selection with the same parameters in every deme. Linkage disequilibrium is neglected. Most of the results concern the covariances of the local averages. For a finite number of demes, explicit formulas are derived for (i) the asymptotic rate and pattern of convergence to equilibrium, (ii) the variance of a suitably weighted average of the local averages, and (iii) the equilibrium covariances when selection and random drift are much weaker than migration. Essentially complete analyses of equilibrium and convergence are presented for random outbreeding and site homing, the Levene and island models, the circular habitat and the unbounded linear stepping-stone model in the diffusion approximation, and the exact unbounded stepping-stone model in one and two dimensions. PMID:8138171

  20. Genotype-by-Diet Interactions Drive Metabolic Phenotype Variation in Drosophila melanogaster

    PubMed Central

    Reed, Laura K.; Williams, Stephanie; Springston, Mastafa; Brown, Julie; Freeman, Kenda; DesRoches, Christie E.; Sokolowski, Marla B.; Gibson, Greg

    2010-01-01

    The rising prevalence of complex disease suggests that alterations to the human environment are increasing the proportion of individuals who exceed a threshold of liability. This might be due either to a global shift in the population mean of underlying contributing traits, or to increased variance of such underlying endophenotypes (such as body weight). To contrast these quantitative genetic mechanisms with respect to weight gain, we have quantified the effect of dietary perturbation on metabolic traits in 146 inbred lines of Drosophila melanogaster and show that genotype-by-diet interactions are pervasive. For several metabolic traits, genotype-by-diet interactions account for far more variance (between 12 and 17%) than diet alone (1–2%), and in some cases have as large an effect as genetics alone (11–23%). Substantial dew point effects were also observed. Larval foraging behavior was found to be a quantitative trait exhibiting significant genetic variation for path length (P = 0.0004). Metabolic and fitness traits exhibited a complex correlation structure, and there was evidence of selection minimizing weight under laboratory conditions. In addition, a high fat diet significantly increases population variance in metabolic phenotypes, suggesting decreased robustness in the face of dietary perturbation. Changes in metabolic trait mean and variance in response to diet indicates that shifts in both population mean and variance in underlying traits could contribute to increases in complex disease. PMID:20385784

  1. Resource variation and the evolution of phenotypic plasticity in fishes

    E-print Network

    Ruehl, Clifton Benjamin

    2004-09-30

    variation. The first empirical study addresses trophic plasticity, population divergence, and the effect of fine-scale environmental variation in western mosquitofish (Gambusia affinis). Offspring from two populations were fed either attached or unattached...

  2. Phenotypic Variation and FMRP Levels in Fragile X

    ERIC Educational Resources Information Center

    Loesch, Danuta Z.; Huggins, Richard M.; Hagerman, Randi J.

    2004-01-01

    Data on the relationships between cognitive and physical phenotypes, and a deficit of fragile X mental retardation 1 (FMR1) gene-specific protein product, FMRP, are presented and discussed in context with earlier findings. The previously unpublished results obtained, using standard procedures of regression and correlations, showed highly…

  3. Conflicting selection from an antagonist and a mutualist enhances phenotypic variation in a plant.

    PubMed

    Siepielski, Adam M; Benkman, Craig W

    2010-04-01

    The raw material for evolution is variation. Consequently, identifying the factors that generate, maintain, and erode phenotypic and genetic variation in ecologically important traits within and among populations is important. Although persistent directional or stabilizing selection can deplete variation, spatial variation in conflicting directional selection can enhance variation. Here, we present evidence that phenotypic variation in limber pine (Pinus flexilis) cone structure is enhanced by conflicting selection pressures exerted by its mutualistic seed disperser (Clark's nutcracker Nucifraga columbiana) and an antagonistic seed predator (pine squirrel Tamiasciurus spp.). Phenotypic variation in cone structure was bimodal and about two times greater where both agents of selection co-occurred than where one (the seed predator) was absent. Within the region where both agents of selection co-occurred, bimodality in cone structure was pronounced where there appears to be a mosaic of habitats with some persistent habitats supporting only the seed disperser. These results indicate that conflicting selection stemming from spatial variation in community diversity can enhance phenotypic variation in ecologically important traits. PMID:19817846

  4. Classification of African plantain landraces and banana cultivars using a phenotypic distance index of quantitative descriptors

    Microsoft Academic Search

    R. Ortiz; S. Madsen; D. Vuylsteke

    1998-01-01

    Proper classification and establishment of relationships between and within Musa taxonomic clusters will be important tools for the genetic improvement of plantain and banana. This paper assesses the value\\u000a of a phenotypic diversity index, based on 16 quantitative descriptors, for germplasm clustering and for identification of\\u000a duplicates among 92 triploid plantain and banana accessions. Data were recorded during the plant

  5. Human olfaction: from genomic variation to phenotypic diversity

    Microsoft Academic Search

    Yehudit Hasin-Brumshtein; Doron Lancet; Tsviya Olender

    2009-01-01

    The sense of smell is a complex molecular device, encompassing several hundred olfactory receptor proteins (ORs). These receptors, encoded by the largest human gene superfamily, integrate odorant signals into an accurate 'odor image' in the brain. Widespread phe- notypic diversity in human olfaction is, in part, attribu- table to prevalent genetic variation in OR genes, owing to copy number variation,

  6. Quantitative Genetic Bases of Anthocyanin Variation in Grape (Vitis vinifera L. ssp. sativa) Berry: A Quantitative Trait Locus to Quantitative Trait Nucleotide Integrated Study

    PubMed Central

    Fournier-Level, Alexandre; Le Cunff, Loïc; Gomez, Camila; Doligez, Agnès; Ageorges, Agnès; Roux, Catherine; Bertrand, Yves; Souquet, Jean-Marc; Cheynier, Véronique; This, Patrice

    2009-01-01

    The combination of QTL mapping studies of synthetic lines and association mapping studies of natural diversity represents an opportunity to throw light on the genetically based variation of quantitative traits. With the positional information provided through quantitative trait locus (QTL) mapping, which often leads to wide intervals encompassing numerous genes, it is now feasible to directly target candidate genes that are likely to be responsible for the observed variation in completely sequenced genomes and to test their effects through association genetics. This approach was performed in grape, a newly sequenced genome, to decipher the genetic architecture of anthocyanin content. Grapes may be either white or colored, ranging from the lightest pink to the darkest purple tones according to the amount of anthocyanin accumulated in the berry skin, which is a crucial trait for both wine quality and human nutrition. Although the determinism of the white phenotype has been fully identified, the genetic bases of the quantitative variation of anthocyanin content in berry skin remain unclear. A single QTL responsible for up to 62% of the variation in the anthocyanin content was mapped on a Syrah × Grenache F1 pseudo-testcross. Among the 68 unigenes identified in the grape genome within the QTL interval, a cluster of four Myb-type genes was selected on the basis of physiological evidence (VvMybA1, VvMybA2, VvMybA3, and VvMybA4). From a core collection of natural resources (141 individuals), 32 polymorphisms revealed significant association, and extended linkage disequilibrium was observed. Using a multivariate regression method, we demonstrated that five polymorphisms in VvMybA genes except VvMybA4 (one retrotransposon, three single nucleotide polymorphisms and one 2-bp insertion/deletion) accounted for 84% of the observed variation. All these polymorphisms led to either structural changes in the MYB proteins or differences in the VvMybAs promoters. We concluded that the continuous variation in anthocyanin content in grape was explained mainly by a single gene cluster of three VvMybA genes. The use of natural diversity helped to reduce one QTL to a set of five quantitative trait nucleotides and gave a clear picture of how isogenes combined their effects to shape grape color. Such analysis also illustrates how isogenes combine their effect to shape a complex quantitative trait and enables the definition of markers directly targeted for upcoming breeding programs. PMID:19720862

  7. Impact of temporal variation on design and analysis of mouse knockout phenotyping studies.

    PubMed

    Karp, Natasha A; Speak, Anneliese O; White, Jacqueline K; Adams, David J; Hrabé de Angelis, Martin; Hérault, Yann; Mott, Richard F

    2014-01-01

    A significant challenge facing high-throughput phenotyping of in-vivo knockout mice is ensuring phenotype calls are robust and reliable. Central to this problem is selecting an appropriate statistical analysis that models both the experimental design (the workflow and the way control mice are selected for comparison with knockout animals) and the sources of variation. Recently we proposed a mixed model suitable for small batch-oriented studies, where controls are not phenotyped concurrently with mutants. Here we evaluate this method both for its sensitivity to detect phenotypic effects and to control false positives, across a range of workflows used at mouse phenotyping centers. We found the sensitivity and control of false positives depend on the workflow. We show that the phenotypes in control mice fluctuate unexpectedly between batches and this can cause the false positive rate of phenotype calls to be inflated when only a small number of batches are tested, when the effect of knockout becomes confounded with temporal fluctuations in control mice. This effect was observed in both behavioural and physiological assays. Based on this analysis, we recommend two approaches (workflow and accompanying control strategy) and associated analyses, which would be robust, for use in high-throughput phenotyping pipelines. Our results show the importance in modelling all sources of variability in high-throughput phenotyping studies. PMID:25343444

  8. Impact of Temporal Variation on Design and Analysis of Mouse Knockout Phenotyping Studies

    PubMed Central

    Karp, Natasha A.; Speak, Anneliese O.; White, Jacqueline K.; Adams, David J.; Hrabé de Angelis, Martin; Hérault, Yann; Mott, Richard F.

    2014-01-01

    A significant challenge facing high-throughput phenotyping of in-vivo knockout mice is ensuring phenotype calls are robust and reliable. Central to this problem is selecting an appropriate statistical analysis that models both the experimental design (the workflow and the way control mice are selected for comparison with knockout animals) and the sources of variation. Recently we proposed a mixed model suitable for small batch-oriented studies, where controls are not phenotyped concurrently with mutants. Here we evaluate this method both for its sensitivity to detect phenotypic effects and to control false positives, across a range of workflows used at mouse phenotyping centers. We found the sensitivity and control of false positives depend on the workflow. We show that the phenotypes in control mice fluctuate unexpectedly between batches and this can cause the false positive rate of phenotype calls to be inflated when only a small number of batches are tested, when the effect of knockout becomes confounded with temporal fluctuations in control mice. This effect was observed in both behavioural and physiological assays. Based on this analysis, we recommend two approaches (workflow and accompanying control strategy) and associated analyses, which would be robust, for use in high-throughput phenotyping pipelines. Our results show the importance in modelling all sources of variability in high-throughput phenotyping studies. PMID:25343444

  9. Quantitative genetic models for describing simultaneous and recursive relationships between phenotypes.

    PubMed Central

    Gianola, Daniel; Sorensen, Daniel

    2004-01-01

    Multivariate models are of great importance in theoretical and applied quantitative genetics. We extend quantitative genetic theory to accommodate situations in which there is linear feedback or recursiveness between the phenotypes involved in a multivariate system, assuming an infinitesimal, additive, model of inheritance. It is shown that structural parameters defining a simultaneous or recursive system have a bearing on the interpretation of quantitative genetic parameter estimates (e.g., heritability, offspring-parent regression, genetic correlation) when such features are ignored. Matrix representations are given for treating a plethora of feedback-recursive situations. The likelihood function is derived, assuming multivariate normality, and results from econometric theory for parameter identification are adapted to a quantitative genetic setting. A Bayesian treatment with a Markov chain Monte Carlo implementation is suggested for inference and developed. When the system is fully recursive, all conditional posterior distributions are in closed form, so Gibbs sampling is straightforward. If there is feedback, a Metropolis step may be embedded for sampling the structural parameters, since their conditional distributions are unknown. Extensions of the model to discrete random variables and to nonlinear relationships between phenotypes are discussed. PMID:15280252

  10. Quantitative phenotyping of X-disease resistance in chokecherry using real-time PCR.

    PubMed

    Huang, Danqiong; Walla, James A; Dai, Wenhao

    2014-03-01

    A quantitative real-time SYBR Green PCR (qPCR) assay has been developed to detect and quantify X-disease phytoplasmas in chokecherry. An X-disease phytoplasma-specific and high sensitivity primer pair was designed based on the 16S rRNA gene sequence of X-disease phytoplasmas. This primer pair was specific to the 16SrIII group (X-disease) phytoplasmas. The qPCR method can quantify phytoplasmas from a DNA mix (a mix of both chokecherry and X-disease phytoplasma DNA) at as low as 0.001 ng, 10-fold lower than conventional PCR using the same primer pair. A significant correlation between the copy number of phytoplasmas and visual phenotypic rating scores of X-disease resistance in chokecherry plants was observed. Disease resistant chokecherries had a significantly lower titer of X-disease phytoplasmas than susceptible plants. This suggests that the qPCR assay provides a more objective tool to phenotype phytoplasma disease severity, particularly for early evaluation of host resistance; therefore, this method will facilitate quantitative phenotyping of disease resistance and has great potential in enhancing plant breeding. PMID:24389037

  11. Evolution of phenotypic plasticity and environmental tolerance of a labile quantitative character in a fluctuating environment.

    PubMed

    Lande, R

    2014-05-01

    Quantitative genetic models of evolution of phenotypic plasticity are used to derive environmental tolerance curves for a population in a changing environment, providing a theoretical foundation for integrating physiological and community ecology with evolutionary genetics of plasticity and norms of reaction. Plasticity is modelled for a labile quantitative character undergoing continuous reversible development and selection in a fluctuating environment. If there is no cost of plasticity, a labile character evolves expected plasticity equalling the slope of the optimal phenotype as a function of the environment. This contrasts with previous theory for plasticity influenced by the environment at a critical stage of early development determining a constant adult phenotype on which selection acts, for which the expected plasticity is reduced by the environmental predictability over the discrete time lag between development and selection. With a cost of plasticity in a labile character, the expected plasticity depends on the cost and on the environmental variance and predictability averaged over the continuous developmental time lag. Environmental tolerance curves derived from this model confirm traditional assumptions in physiological ecology and provide new insights. Tolerance curve width increases with larger environmental variance, but can only evolve within a limited range. The strength of the trade-off between tolerance curve height and width depends on the cost of plasticity. Asymmetric tolerance curves caused by male sterility at high temperature are illustrated. A simple condition is given for a large transient increase in plasticity and tolerance curve width following a sudden change in average environment. PMID:24724972

  12. Genetic influence on immune phenotype revealed strain-specific variations in peripheral blood lineages

    Microsoft Academic Search

    Stefka B. Petkova; Rong Yuan; Shirng-Wern Tsaih; William Schott; Derry C. Roopenian; Beverly Paigen

    2008-01-01

    Inbred mouse strains are routinely used as genetically defined animal models for studying a wide assortment of biological and pathological processes, including immune system function. However, no studies have presented large-scale data on the immune cell populations among the inbred strains in physiological conditions. Here we present a systematic, quantitative analysis of peripheral blood cell phenotypes of 30 mouse strains

  13. Optimizing experimental procedures for quantitative evaluation of crop plant performance in high throughput phenotyping systems.

    PubMed

    Junker, Astrid; Muraya, Moses M; Weigelt-Fischer, Kathleen; Arana-Ceballos, Fernando; Klukas, Christian; Melchinger, Albrecht E; Meyer, Rhonda C; Riewe, David; Altmann, Thomas

    2014-01-01

    Detailed and standardized protocols for plant cultivation in environmentally controlled conditions are an essential prerequisite to conduct reproducible experiments with precisely defined treatments. Setting up appropriate and well defined experimental procedures is thus crucial for the generation of solid evidence and indispensable for successful plant research. Non-invasive and high throughput (HT) phenotyping technologies offer the opportunity to monitor and quantify performance dynamics of several hundreds of plants at a time. Compared to small scale plant cultivations, HT systems have much higher demands, from a conceptual and a logistic point of view, on experimental design, as well as the actual plant cultivation conditions, and the image analysis and statistical methods for data evaluation. Furthermore, cultivation conditions need to be designed that elicit plant performance characteristics corresponding to those under natural conditions. This manuscript describes critical steps in the optimization of procedures for HT plant phenotyping systems. Starting with the model plant Arabidopsis, HT-compatible methods were tested, and optimized with regard to growth substrate, soil coverage, watering regime, experimental design (considering environmental inhomogeneities) in automated plant cultivation and imaging systems. As revealed by metabolite profiling, plant movement did not affect the plants' physiological status. Based on these results, procedures for maize HT cultivation and monitoring were established. Variation of maize vegetative growth in the HT phenotyping system did match well with that observed in the field. The presented results outline important issues to be considered in the design of HT phenotyping experiments for model and crop plants. It thereby provides guidelines for the setup of HT experimental procedures, which are required for the generation of reliable and reproducible data of phenotypic variation for a broad range of applications. PMID:25653655

  14. Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women

    PubMed Central

    Ridderstråle, Martin; Gerdhem, Paul; Luthman, Holger; Åkesson, Kristina

    2014-01-01

    Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n?=?1061) and OPRA (age 75, n?=?1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r2?=?0.2–0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs. CC: BUA: 100 vs. 103 vs. 103; p?=?0.002); (SOS: 1521 vs. 1526 vs. 1524; p?=?0.008); (Stiffness index: 69 vs. 73 vs. 74; p?=?0.0006) after adjustment for confounders. They also had low folate (18 vs. 17 vs. 16; p?=?0.03) and vitamin D (93 vs. 91 vs. 90; p?=?0.03) and high Hcy levels (13.7 vs 14.4 vs. 14.5; p?=?0.06). Fracture incidence was lower among women with the C-allele, (52% vs. 58%; p?=?0.067). Variation in MC4R was not associated with BMD or body composition in either OPRA or PEAK-25. SNPs close to FTO and INSIG2 were not associated with any bone phenotypes in either cohort and FTO SNPs were only associated with body composition in PEAK-25 (p?0.001). Our results suggest that genetic variation close to MC4R is associated with quantitative ultrasound and risk of fracture. PMID:24516669

  15. Adrenocortical responses in zebra finches (Taeniopygia guttata): individual variation, repeatability, and relationship to phenotypic quality.

    PubMed

    Wada, Haruka; Salvante, Katrina G; Stables, Christine; Wagner, Emily; Williams, Tony D; Breuner, Creagh W

    2008-03-01

    Although individual variation is a key requirement for natural selection, little is known about the magnitude and patterns of individual variation in endocrine systems or the functional significance of that variation. Here we describe (1) the extent and repeatability of inter-individual variation in adrenocortical responses and (2) its relationship to sex-specific phenotypic quality, such as song duration and frequency and timing of egg laying. We measured adrenocortical responses to a standardized stressor in zebra finches (Taeniopygia guttata) at two life history stages: approximately day 16 (nestlings) and 3 months of age (sexually mature adults). Subsequently, we assessed phenotypic (reproductive) quality of all individuals as adults. Marked inter-individual variation in the adrenocortical response was seen in both sexes and ages, e.g., stress-induced corticosterone ranged from 2.2 to 62.5 ng/mL in nestlings and 5.0-64.0 ng/mL in adults. We found sex differences in (a) inter-individual variation in the adrenocortical response, (b) repeatability, and (c) relationships between corticosterone levels and phenotypic quality. In males, variation in nestling corticosterone was weakly but positively correlated with brood size and negatively correlated with nestling mass (though this relationship was dependent on one individual). There was no significant correlation of adrenocortical responses between two stages in males and adult phenotypic quality was significantly correlated only with adult corticosterone levels. In contrast, in females there was no relationship between nestling corticosterone and brood size or mass but adrenocortical response was repeatable between two stages (r2=0.413). Phenotypic quality of adult females was correlated with nestling baseline and adrenocortical response. PMID:18221739

  16. Relevance of phenotypic variation in risk assessment: The scientific viewpoint

    SciTech Connect

    Setlow, R.B.

    1986-01-01

    A number of examples are presented indicating the types of variation that may be expected in the responses of the human population to deleterious agents of an endogeneous or exogenous nature. If one assumes that the variations in repair in the normal population are reflected in large variations in carcinogenic risk per unit of exposure, then the dose-response curves at low doses cannot be extrapolated from high doeses without knowing the distribution of sensitivities among humans. The probability of determining this range by ecpidemiological studies on a random population by small. On the other hand, the probability of determining the range by careful genetic and molecular studies appears high enough so that such experiments now are being carried out. They cannot be carried out on real populations, using chronic exposures. Hence, the ability to estimate dose-response relations in the low dose region on human populations can only be by making theoretical constructs that, in turn, are dependent on fundamental research. 12 refs., 2 tabs.

  17. ClinVar: public archive of relationships among sequence variation and human phenotype.

    PubMed

    Landrum, Melissa J; Lee, Jennifer M; Riley, George R; Jang, Wonhee; Rubinstein, Wendy S; Church, Deanna M; Maglott, Donna R

    2014-01-01

    ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations. PMID:24234437

  18. ClinVar: public archive of relationships among sequence variation and human phenotype

    PubMed Central

    Landrum, Melissa J.; Lee, Jennifer M.; Riley, George R.; Jang, Wonhee; Rubinstein, Wendy S.; Church, Deanna M.; Maglott, Donna R.

    2014-01-01

    ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations. PMID:24234437

  19. Molecular and quantitative trait variation within and among small fragmented populations of the endangered plant species Psilopeganum sinense

    PubMed Central

    Ye, Qigang; Tang, Feiyan; Wei, Na; Yao, Xiaohong

    2014-01-01

    Background and Aims Natural selection and genetic drift are important evolutionary forces in determining genetic and phenotypic differentiation in plant populations. The extent to which these two distinct evolutionary forces affect locally adaptive quantitative traits has been well studied in common plant and animal species. However, we know less about how quantitative traits respond to selection pressures and drift in endangered species that have small population sizes and fragmented distributions. To address this question, this study assessed the relative strengths of selection and genetic drift in shaping population differentiation of phenotypic traits in Psilopeganum sinense, a naturally rare and recently endangered plant species. Methods Population differentiation at five quantitative traits (QST) obtained from a common garden experiment was compared with differentiation at putatively neutral microsatellite markers (FST) in seven populations of P. sinense. QST estimates were derived using a Bayesian hierarchical variance component method. Key Results Trait-specific QST values were equal to or lower than FST. Neutral genetic diversity was not correlated with quantitative genetic variation within the populations of P. sinense. Conclusions Despite the prevalent empirical evidence for QST > FST, the results instead suggest a definitive role of stabilizing selection and drift leading to phenotypic differentiation among small populations. Three traits exhibited a significantly lower QST relative to FST, suggesting that populations of P. sinense might have experienced stabilizing selection for the same optimal phenotypes despite large geographical distances between populations and habitat fragmentation. For the other two traits, QST estimates were of the same magnitude as FST, indicating that divergence in these traits could have been achieved by genetic drift alone. The lack of correlation between molecular marker and quantitative genetic variation suggests that sophisticated considerations are required for the inference of conservation measures of P. sinense from neutral genetic markers. PMID:24265350

  20. Classification of Human Chromosome 21 Gene-Expression Variations in Down Syndrome: Impact on Disease Phenotypes

    Microsoft Academic Search

    E. Aït Yahya-Graison; J. Aubert; L. Dauphinot; I. Rivals; M. Prieur; G. Golfier; J. Rossier; L. Personnaz; N. Créau; H. Bléhaut; S. Robin; J. M. Delabar; M.-C. Potier

    2007-01-01

    Down syndrome caused by chromosome 21 trisomy is the most common genetic cause of mental retardation in humans. Disruption of the phenotype is thought to be the result of gene-dosage imbalance. Variations in chromosome 21 gene expression in Down syndrome were analyzed in lymphoblastoid cells derived from patients and control individuals. Of the 359 genes and predictions displayed on a

  1. Natural Variation in MAM Within and Between Populations of Arabidopsis lyrata Determines Glucosinolate Phenotype

    Microsoft Academic Search

    Andrew J. Heidel; Maria J. Clauss; Juergen Kroymann; Outi Savolainen; Thomas Mitchell-Olds

    2006-01-01

    The genetic variation that underlies the glucosinolate phenotype of Arabidopsis lyrata ssp. petraea was investigated between and within populations. A candidate glucosinolate biosynthetic locus (MAM, con- taining methylthioalkylmalate synthase genes) was mapped in A. lyrata to a location on linkage group 6 corresponding to the homologous location for MAM in A. thaliana .I nA. thaliana MAM is responsible for side

  2. The Role of Inflammatory Pathway Genetic Variation on Maternal Metabolic Phenotypes during Pregnancy

    Microsoft Academic Search

    Margrit Urbanek; M. Geoffrey Hayes; Hoon Lee; Rachel M. Freathy; Lynn P. Lowe; Christine Ackerman; Nadereh Jafari; Alan R. Dyer; Nancy J. Cox; David B. Dunger; Andrew T. Hattersley; Boyd E. Metzger; William L. Lowe

    2012-01-01

    BackgroundSince mediators of inflammation are associated with insulin resistance, and the risk of developing diabetes mellitus and gestational diabetes, we hypothesized that genetic variation in members of the inflammatory gene pathway impact glucose levels and related phenotypes in pregnancy. We evaluated this hypothesis by testing for association between genetic variants in 31 inflammatory pathway genes in the Hyperglycemia and Adverse

  3. Temporal Variation in Phenotypic and Genotypic Traits in Two Sockeye Salmon Populations, Tustumena Lake, Alaska

    Microsoft Academic Search

    Carol Ann Woody; Jeff Olsen; Joel Reynolds; Paul Bentzen

    2000-01-01

    Sockeye salmon Oncorhynchus nerka in two tributary streams (about 20 km apart) of the same lake were compared for temporal variation in phenotypic (length, depth adjusted for length) and genotypic (six microsatellite loci) traits. Peak run time (July 16 versus 11 August) and run duration (43 versus 26 d) differed between streams. Populations were sampled twice, including an overlapping point

  4. Genomic Plasticity Enables Phenotypic Variation of Pseudomonas syringae pv. tomato DC3000

    E-print Network

    Myers, Chris

    Genomic Plasticity Enables Phenotypic Variation of Pseudomonas syringae pv. tomato DC3000 Zhongmeng University, Ithaca, New York, United States of America Abstract Whole genome sequencing revealed the presence of a genomic anomaly in the region of 4.7 to 4.9 Mb of the Pseudomonas syringae pv. tomato (Pst) DC3000 genome

  5. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach

    PubMed Central

    Aerts, Hugo J. W. L.; Velazquez, Emmanuel Rios; Leijenaar, Ralph T. H.; Parmar, Chintan; Grossmann, Patrick; Cavalho, Sara; Bussink, Johan; Monshouwer, René; Haibe-Kains, Benjamin; Rietveld, Derek; Hoebers, Frank; Rietbergen, Michelle M.; Leemans, C. René; Dekker, Andre; Quackenbush, John; Gillies, Robert J.; Lambin, Philippe

    2014-01-01

    Human cancers exhibit strong phenotypic differences that can be visualized noninvasively by medical imaging. Radiomics refers to the comprehensive quantification of tumour phenotypes by applying a large number of quantitative image features. Here we present a radiomic analysis of 440 features quantifying tumour image intensity, shape and texture, which are extracted from computed tomography data of 1,019 patients with lung or head-and-neck cancer. We find that a large number of radiomic features have prognostic power in independent data sets of lung and head-and-neck cancer patients, many of which were not identified as significant before. Radiogenomics analysis reveals that a prognostic radiomic signature, capturing intratumour heterogeneity, is associated with underlying gene-expression patterns. These data suggest that radiomics identifies a general prognostic phenotype existing in both lung and head-and-neck cancer. This may have a clinical impact as imaging is routinely used in clinical practice, providing an unprecedented opportunity to improve decision-support in cancer treatment at low cost. PMID:24892406

  6. A formal perturbation equation between genotype and phenotype determines the Evolutionary Action of protein-coding variations on fitness

    PubMed Central

    Katsonis, Panagiotis

    2014-01-01

    The relationship between genotype mutations and phenotype variations determines health in the short term and evolution over the long term, and it hinges on the action of mutations on fitness. A fundamental difficulty in determining this action, however, is that it depends on the unique context of each mutation, which is complex and often cryptic. As a result, the effect of most genome variations on molecular function and overall fitness remains unknown and stands apart from population genetics theories linking fitness effect to polymorphism frequency. Here, we hypothesize that evolution is a continuous and differentiable physical process coupling genotype to phenotype. This leads to a formal equation for the action of coding mutations on fitness that can be interpreted as a product of the evolutionary importance of the mutated site with the difference in amino acid similarity. Approximations for these terms are readily computable from phylogenetic sequence analysis, and we show mutational, clinical, and population genetic evidence that this action equation predicts the effect of point mutations in vivo and in vitro in diverse proteins, correlates disease-causing gene mutations with morbidity, and determines the frequency of human coding polymorphisms, respectively. Thus, elementary calculus and phylogenetics can be integrated into a perturbation analysis of the evolutionary relationship between genotype and phenotype that quantitatively links point mutations to function and fitness and that opens a new analytic framework for equations of biology. In practice, this work explicitly bridges molecular evolution with population genetics with applications from protein redesign to the clinical assessment of human genetic variations. PMID:25217195

  7. Sources of Variation in Quantitative Computed Tomography of the Lung

    PubMed Central

    Coxson, Harvey O

    2013-01-01

    Summary The goal of quantitative analysis of computed tomography (CT) scans is to understand the anatomic structure that is responsible for the physiological function of the lung. While the gold standard for structural analysis requires the examination of tissue this is not practical in most studies. Quantitative CT allows a method to obtain valuable information on lung structure without having to remove tissue from the body thereby allowing longitudinal studies of chronic lung diseases. This review briefly discusses CT analysis of the lung and some of the sources of variation that can cause differences in the CT metrics used for analysis of lung disease. While there are many sources of variation the purpose of this review will show that if the study is properly designed to take into account these variations and the CT scanner is properly calibrated valuable information can be obtained from CT scans that should allow us to study the pathogenesis of lung disease and the effect of treatment. PMID:23934141

  8. Exploration of methods to identify polymorphisms associated with variation in DNA repair capacity phenotypes

    SciTech Connect

    Jones, I M; Thomas, C B; Xi, T; Mohrenweiser, H W; Nelson, D O

    2006-07-03

    Elucidating the relationship between polymorphic sequences and risk of common disease is a challenge. For example, although it is clear that variation in DNA repair genes is associated with familial cancer, aging and neurological disease, progress toward identifying polymorphisms associated with elevated risk of sporadic disease has been slow. This is partly due to the complexity of the genetic variation, the existence of large numbers of mostly low frequency variants and the contribution of many genes to variation in susceptibility. There has been limited development of methods to find associations between genotypes having many polymorphisms and pathway function or health outcome. We have explored several statistical methods for identifying polymorphisms associated with variation in DNA repair phenotypes. The model system used was 80 cell lines that had been resequenced to identify variation; 191 single nucleotide substitution polymorphisms (SNPs) are included, of which 172 are in 31 base excision repair pathway genes, 19 in 5 anti-oxidation genes, and DNA repair phenotypes based on single strand breaks measured by the alkaline Comet assay. Univariate analyses were of limited value in identifying SNPs associated with phenotype variation. Of the multivariable model selection methods tested: the easiest that provided reduced error of prediction of phenotype was simple counting of the variant alleles predicted to encode proteins with reduced activity, which led to a genotype including 52 SNPs; the best and most parsimonious model was achieved using a two-step analysis without regard to potential functional relevance: first SNPs were ranked by importance determined by Random Forests Regression (RFR), followed by cross-validation in a second round of RFR modeling that included ever more SNPs in declining order of importance. With this approach 6 SNPs were found to minimize prediction error. The results should encourage research into utilization of multivariate analytical methods for epidemiological studies of the association of genetic variation in complex genotypes with risk of common diseases.

  9. Genotypic and phenotypic variation of Lewis antigen expression in geographically diverse Helicobacter pylori isolates

    PubMed Central

    Pohl, Mary Ann; Zhang, William; Shah, Sunny; Sanabria-Valentín, Edgardo L.; Perez-Perez, Guillermo I.; Blaser, Martin J.

    2011-01-01

    Background Helicobacter pylori is a persistent colonizer of the human gastric mucosa, which can lead to the development peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, since humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. Materials and Methods From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains, and performed genotyping of the galT and ?-(1,3)galT loci in 113 H. pylori strains. Results Le antigen phenotyping revealed a significant (p <0.0001) association between type 1 (Lea and Leb) expression and strains of East-Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p <0.0001). Conclusion These results indicate that the heterogeneity of human Le phenotypes are reflected in their H. pylori colonizing strains, and suggest new loci that can be studied to assess variation of Le expression. PMID:22059399

  10. [The floral meristem undetermination mutation in Papaver somniferum L.: spontaneous phenotypic variation in ontogeny].

    PubMed

    Beliaeva, R G

    2008-01-01

    A new morphogenetic mutation of the shoot, floral meristem undetermination, was found in Papaver somniferum L. with monocarpic shoot. The expression of the DFM (determination of floral meristem) gene, which limits the proliferative activity of stem cells in the floral meristem, was affected. The mutation displayed spontaneous phenotypic instability in ontogeny, variation in the mutant character expression on different flowers of the same plant in the same genotypic environment. The mutation phenotype varied from no expression or formation of individual phyllomes in the center of the primary ovary to formation of a new flower and a new capsule with viable seeds. PMID:18669291

  11. Intraspecific phenotypic variation in a fish predator affects multitrophic lake metacommunity structure

    PubMed Central

    Howeth, Jennifer G; Weis, Jerome J; Brodersen, Jakob; Hatton, Elizabeth C; Post, David M

    2013-01-01

    Contemporary insights from evolutionary ecology suggest that population divergence in ecologically important traits within predators can generate diversifying ecological selection on local community structure. Many studies acknowledging these effects of intraspecific variation assume that local populations are situated in communities that are unconnected to similar communities within a shared region. Recent work from metacommunity ecology suggests that species dispersal among communities can also influence species diversity and composition but can depend upon the relative importance of the local environment. Here, we study the relative effects of intraspecific phenotypic variation in a fish predator and spatial processes related to plankton species dispersal on multitrophic lake plankton metacommunity structure. Intraspecific diversification in foraging traits and residence time of the planktivorous fish alewife (Alosa pseudoharengus) among coastal lakes yields lake metacommunities supporting three lake types which differ in the phenotype and incidence of alewife: lakes with anadromous, landlocked, or no alewives. In coastal lakes, plankton community composition was attributed to dispersal versus local environmental predictors, including intraspecific variation in alewives. Local and beta diversity of zooplankton and phytoplankton was additionally measured in response to intraspecific variation in alewives. Zooplankton communities were structured by species sorting, with a strong influence of intraspecific variation in A. pseudoharengus. Intraspecific variation altered zooplankton species richness and beta diversity, where lake communities with landlocked alewives exhibited intermediate richness between lakes with anadromous alewives and without alewives, and greater community similarity. Phytoplankton diversity, in contrast, was highest in lakes with landlocked alewives. The results indicate that plankton dispersal in the region supplied a migrant pool that was strongly structured by intraspecific variation in alewives. This is one of the first studies to demonstrate that intraspecific phenotypic variation in a predator can maintain contrasting patterns of multitrophic diversity in metacommunities. PMID:24455134

  12. Cone and Seed Trait Variation in Whitebark Pine (Pinus Albicaulis; Pinaceae) and the Potential for Phenotypic Selection

    Microsoft Academic Search

    R. Garcia; A. M. Siepielski; Craig Benkman

    2009-01-01

    Phenotypic variation among, individuals is necessary for natural selection to operate and is therefore essential for adaptive evolution. However, extensive variation within individuals can mask variation among individuals and weaken the potential for selection. Here we quantify variation among within individuals in female cone and seed traits of whitebark pine (Pinus albicaulis). In many plants the production of numerous reproductive

  13. MSH1-Induced Non-Genetic Variation Provides a Source of Phenotypic Diversity in Sorghum bicolor

    PubMed Central

    Wang, Guomei; Nino-Liu, David O.; Kundariya, Hardik; Wamboldt, Yashitola; Dweikat, Ismail; Mackenzie, Sally A.

    2014-01-01

    MutS Homolog 1 (MSH1) encodes a plant-specific protein that functions in mitochondria and chloroplasts. We showed previously that disruption or suppression of the MSH1 gene results in a process of developmental reprogramming that is heritable and non-genetic in subsequent generations. In Arabidopsis, this developmental reprogramming process is accompanied by striking changes in gene expression of organellar and stress response genes. This developmentally reprogrammed state, when used in crossing, results in a range of variation for plant growth potential. Here we investigate the implications of MSH1 modulation in a crop species. We found that MSH1-mediated phenotypic variation in Sorghum bicolor is heritable and potentially valuable for crop breeding. We observed phenotypic variation for grain yield, plant height, flowering time, panicle architecture, and above-ground biomass. Focusing on grain yield and plant height, we found some lines that appeared to respond to selection. Based on amenability of this system to implementation in a range of crops, and the scope of phenotypic variation that is derived, our results suggest that MSH1 suppression provides a novel approach for breeding in crops. PMID:25347794

  14. Divergence in a master variator generates distinct phenotypes and transcriptional responses

    PubMed Central

    Gallagher, Jennifer E.G.; Zheng, Wei; Rong, Xiaoqing; Miranda, Noraliz; Lin, Zhixiang; Dunn, Barbara; Zhao, Hongyu; Snyder, Michael P.

    2014-01-01

    Genetic basis of phenotypic differences in individuals is an important area in biology and personalized medicine. Analysis of divergent Saccharomyces cerevisiae strains grown under different conditions revealed extensive variation in response to both drugs (e.g., 4-nitroquinoline 1-oxide [4NQO]) and different carbon sources. Differences in 4NQO resistance were due to amino acid variation in the transcription factor Yrr1. Yrr1YJM789 conferred 4NQO resistance but caused slower growth on glycerol, and vice versa with Yrr1S96, indicating that alleles of Yrr1 confer distinct phenotypes. The binding targets of Yrr1 alleles from diverse yeast strains varied considerably among different strains grown under the same conditions as well as for the same strain under different conditions, indicating that distinct molecular programs are conferred by the different Yrr1 alleles. Our results demonstrate that genetic variations in one important control gene (YRR1), lead to distinct regulatory programs and phenotypes in individuals. We term these polymorphic control genes “master variators.” PMID:24532717

  15. Adaptive basis of geographic variation: genetic, phenotypic and environmental differences among beach mouse populations

    PubMed Central

    Mullen, Lynne M.; Vignieri, Sacha N.; Gore, Jeffery A.; Hoekstra, Hopi E.

    2009-01-01

    A major goal in evolutionary biology is to understand how and why populations differentiate, both genetically and phenotypically, as they invade a novel habitat. A classical example of adaptation is the pale colour of beach mice, relative to their dark mainland ancestors, which colonized the isolated sandy dunes and barrier islands on Florida's Gulf Coast. However, much less is known about differentiation among the Gulf Coast beach mice, which comprise five subspecies linearly arrayed on Florida's shoreline. Here, we test the role of selection in maintaining variation among these beach mouse subspecies at multiple levels—phenotype, genotype and the environments they inhabit. While all beach subspecies have light pelage, they differ significantly in colour pattern. These subspecies are also genetically distinct: pair-wise Fst-values range from 0.23 to 0.63 and levels of gene flow are low. However, we did not find a correlation between phenotypic and genetic distance. Instead, we find a significant association between the average ‘lightness’ of each subspecies and the brightness of the substrate it inhabits: the two most genetically divergent subspecies occupy the most similar habitats and have converged on phenotype, whereas the most genetically similar subspecies occupy the most different environments and have divergent phenotypes. Moreover, allelic variation at the pigmentation gene, Mc1r, is statistically correlated with these colour differences but not with variation at other genetic loci. Together, these results suggest that natural selection for camouflage—via changes in Mc1r allele frequency—contributes to pigment differentiation among beach mouse subspecies. PMID:19656790

  16. Quantitative phenotyping of leaf margins in three dimensions, demonstrated on KNOTTED and TCP trangenics in Arabidopsis.

    PubMed

    Armon, Shahaf; Yanai, Osnat; Ori, Naomi; Sharon, Eran

    2014-05-01

    The geometry of leaf margins is an important shape characteristic that distinguishes among different leaf phenotypes. Current definitions of leaf shape are qualitative and do not allow quantification of differences in shape between phenotypes. This is especially true for leaves with some non-trivial three-dimensional (3D) configurations. Here we present a novel geometrical method novel geometrical methods to define, measure, and quantify waviness and lobiness of leaves. The method is based on obtaining the curve of the leaf rim from a 3D surface measurement and decomposing its local curvature vector into the normal and geodesic components. We suggest that leaf waviness is associated with oscillating normal curvature along the margins, while lobiness is associated with oscillating geodesic curvature. We provide a way to integrate these local measures into global waviness and lobiness quantities. Using these novel definitions, we analysed the changes in leaf shape of two Arabidopsis genotypes, either as a function of gene mis-expression induction level or as a function of time. These definitions and experimental methods open the way for a more quantitative study of the shape of leaves and other growing slender organs. PMID:24706720

  17. Quantitative phenotyping of leaf margins in three dimensions, demonstrated on KNOTTED and TCP trangenics in Arabidopsis

    PubMed Central

    Sharon, Eran

    2014-01-01

    The geometry of leaf margins is an important shape characteristic that distinguishes among different leaf phenotypes. Current definitions of leaf shape are qualitative and do not allow quantification of differences in shape between phenotypes. This is especially true for leaves with some non-trivial three-dimensional (3D) configurations. Here we present a novel geometrical method novel geometrical methods to define, measure, and quantify waviness and lobiness of leaves. The method is based on obtaining the curve of the leaf rim from a 3D surface measurement and decomposing its local curvature vector into the normal and geodesic components. We suggest that leaf waviness is associated with oscillating normal curvature along the margins, while lobiness is associated with oscillating geodesic curvature. We provide a way to integrate these local measures into global waviness and lobiness quantities. Using these novel definitions, we analysed the changes in leaf shape of two Arabidopsis genotypes, either as a function of gene mis-expression induction level or as a function of time. These definitions and experimental methods open the way for a more quantitative study of the shape of leaves and other growing slender organs. PMID:24706720

  18. Fractal and Transgenerational Genetic Effects on Phenotypic Variation and Disease Risk

    NASA Astrophysics Data System (ADS)

    Nadeau, Joe

    To understand human biology and to manage heritable diseases, a complete picture of the genetic basis for phenotypic variation and disease risk is needed. Unexpectedly however, most of these genetic variants, even for highly heritable traits, continue to elude discovery for poorly understood reasons. The genetics community is actively exploring the usual explanations for missing heritability. But given the extraordinary work that has already been done and the exceptional magnitude of the problem, it seems likely that unconventional genetic properties are involved.

  19. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation.

    PubMed

    Moon, Clara; Baldridge, Megan T; Wallace, Meghan A; Burnham, Carey-Ann D; Virgin, Herbert W; Stappenbeck, Thaddeus S

    2015-05-01

    The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control. In many cases, the microbiota is the presumed cause of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice. In conventionally raised mice, the microbiome is transmitted from the dam. Here we show that microbially driven dichotomous faecal immunoglobulin-A (IgA) levels in wild-type mice within the same facility mimic the effects of chromosomal mutations. We observe in multiple facilities that vertically transmissible bacteria in IgA-low mice dominantly lower faecal IgA levels in IgA-high mice after co-housing or faecal transplantation. In response to injury, IgA-low mice show increased damage that is transferable by faecal transplantation and driven by faecal IgA differences. We find that bacteria from IgA-low mice degrade the secretory component of secretory IgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose faecal IgA as one marker of microbial variability and conclude that co-housing and/or faecal transplantation enables analysis of progeny from different dams. PMID:25686606

  20. Genetic and phenotypic variation across a hybrid zone between ecologically divergent tree squirrels (Tamiasciurus).

    PubMed

    Chavez, Andreas S; Saltzberg, Carl J; Kenagy, G J

    2011-08-01

    A hybrid zone along an environmental gradient should contain a clinal pattern of genetic and phenotypic variation. This occurs because divergent selection in the two parental habitats is typically strong enough to overcome the homogenizing effects of gene flow across the environmental transition. We studied hybridization between two parapatric tree squirrels (Tamiasciurus spp.) across a forest gradient over which the two species vary in coloration, cranial morphology and body size. We sampled 397 individuals at 29 locations across a 600-km transect to seek genetic evidence for hybridization; upon confirming hybridization, we examined levels of genetic admixture in relation to maintenance of phenotypic divergence despite potentially homogenizing gene flow. Applying population assignment analyses to microsatellite data, we found that Tamiasciurus douglasii and T. hudsonicus form two distinct genetic clusters but also hybridize, mostly within transitional forest habitat. Overall, based on this nuclear analysis, 48% of the specimens were characterized as T. douglasii, 9% as hybrids and 43% as T. hudsonicus. Hybrids appeared to be reproductively viable, as evidenced by the presence of later-generation hybrid genotypes. Observed clines in ecologically important phenotypic traits-fur coloration and cranial morphology-were sharper than the cline of putatively neutral mtDNA, which suggests that divergent selection may maintain phenotypic distinctiveness. The relatively recent divergence of these two species (probably late Pleistocene), apparent lack of prezygotic isolating mechanisms and geographic coincidence of cline centres for both genetic and phenotypic variation suggest that environmental factors play a large role in maintaining the distinctiveness of these two species across the hybrid zone. PMID:21771139

  1. Quantitative analysis of ruminal methanogenic microbial populations in beef cattle divergent in phenotypic residual feed intake (RFI) offered contrasting diets

    PubMed Central

    2014-01-01

    Background Methane (CH4) emissions in cattle are an undesirable end product of rumen methanogenic fermentative activity as they are associated not only with negative environmental impacts but also with reduced host feed efficiency. The aim of this study was to quantify total and specific rumen microbial methanogenic populations in beef cattle divergently selected for residual feed intake (RFI) while offered (i) a low energy high forage (HF) diet followed by (ii) a high energy low forage (LF) diet. Ruminal fluid was collected from 14 high (H) and 14 low (L) RFI animals across both dietary periods. Quantitative real time PCR (qRT-PCR) analysis was conducted to quantify the abundance of total and specific rumen methanogenic microbes. Spearman correlation analysis was used to investigate the association between the relative abundance of methanogens and animal performance, rumen fermentation variables and diet digestibility. Results Abundance of methanogens, did not differ between RFI phenotypes. However, relative abundance of total and specific methanogen species was affected (P?variation in CH4 emissions between efficient and inefficient animals, however dietary manipulation can influence the abundance of total and specific methanogen species. PMID:25276350

  2. Quantitative and evolutionary biology of alternative splicing: how changing the mix of alternative transcripts affects phenotypic plasticity and reaction norms

    Microsoft Academic Search

    J H Marden

    2008-01-01

    Alternative splicing (AS) of pre-messenger RNA is a common phenomenon that creates different transcripts from a single gene, and these alternative transcripts affect phenotypes. The majority of AS research has examined tissue and developmental specificity of expression of particular AS transcripts, how this specificity affects cell function, and how aberrant AS is related to disease. Few studies have examined quantitative

  3. Natural diversity in daily rhythms of gene expression contributes to phenotypic variation

    PubMed Central

    de Montaigu, Amaury; Giakountis, Antonis; Rubin, Matthew; Tóth, Réka; Cremer, Frédéric; Sokolova, Vladislava; Porri, Aimone; Reymond, Matthieu; Weinig, Cynthia; Coupland, George

    2015-01-01

    Daily rhythms of gene expression provide a benefit to most organisms by ensuring that biological processes are activated at the optimal time of day. Although temporal patterns of expression control plant traits of agricultural importance, how natural genetic variation modifies these patterns during the day and how precisely these patterns influence phenotypes is poorly understood. The circadian clock regulates the timing of gene expression, and natural variation in circadian rhythms has been described, but circadian rhythms are measured in artificial continuous conditions that do not reflect the complexity of biologically relevant day/night cycles. By studying transcriptional rhythms of the evening-expressed gene GIGANTEA (GI) at high temporal resolution and during day/night cycles, we show that natural variation in the timing of GI expression occurs mostly under long days in 77 Arabidopsis accessions. This variation is explained by natural alleles that alter light sensitivity of GI, specifically in the evening, and that act at least partly independent of circadian rhythms. Natural alleles induce precise changes in the temporal waveform of GI expression, and these changes have detectable effects on PHYTOCHROME INTERACTING FACTOR 4 expression and growth. Our findings provide a paradigm for how natural alleles act within day/night cycles to precisely modify temporal gene expression waveforms and cause phenotypic diversity. Such alleles could confer an advantage by adjusting the activity of temporally regulated processes without severely disrupting the circadian system. PMID:25548158

  4. Propagule Limitation, Disparate Habitat Quality, and Variation in Phenotypic Selection at a Local Species Range Boundary

    PubMed Central

    Moore, Kara A.; Stanton, Maureen L.

    2014-01-01

    Adaptation to novel conditions beyond current range boundaries requires the presence of suitable sites within dispersal range, but may be impeded when emigrants encounter poor habitat and sharply different selection pressures. We investigated fine-scale spatial heterogeneity in ecological dynamics and selection at a local population boundary of the annual plant Gilia tricolor. In two years, we planted G. tricolor seeds in core habitat, margin habitat at the edge of the local range, and exterior habitat in order to measure spatial and temporal variation in habitat quality, opportunity for selection, and selection on phenotypic traits. We found a striking decline in average habitat quality with distance from the population core, yet some migrant seeds were successful in suitable, unoccupied microsites at and beyond the range boundary. Total and direct selection on four out of five measured phenotypic traits varied across habitat zones, as well as between years. Moreover, the margin habitat often exerted unique selection pressures that were not intermediate between core and exterior habitats. This study reveals that a combination of ecological and evolutionary forces, including propagule limitation, variation in habitat quality and spatial heterogeneity in phenotypic selection may reduce opportunities for adaptive range expansion, even across a very local population boundary. PMID:24717472

  5. Effects of genotypic and phenotypic variation on establishment are important for conservation, invasion, and infection biology

    PubMed Central

    Forsman, Anders

    2014-01-01

    There is abundant evidence that the probability of successful establishment in novel environments increases with number of individuals in founder groups and with number of repeated introductions. Theory posits that the genotypic and phenotypic variation among individuals should also be important, but few studies have examined whether founder diversity influences establishment independent of propagule pressure, nor whether the effect is model or context dependent. I summarize the results of 18 experimental studies and report on a metaanalysis that provides strong evidence that higher levels of genotypic and phenotypic diversity in founder groups increase establishment success in plants and animals. The effect of diversity is stronger in experiments carried out under natural conditions in the wild than under seminatural or standardized laboratory conditions. The realization that genetic and phenotypic variation is key to successful establishment may improve the outcome of reintroduction and translocation programs used to vitalize or restore declining and extinct populations. Founder diversity may also improve the ability of invasive species to establish and subsequently spread in environments outside of their native community, and enhance the ability of pathogens and parasites to colonize and invade the environment constituted by their hosts. It is argued that exchange of ideas, methodological approaches, and insights of the role of diversity for establishment in different contexts may further our knowledge, vitalize future research, and improve management plans in different disciplines. PMID:24367109

  6. The Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease.

    PubMed

    Shimoyama, Mary; De Pons, Jeff; Hayman, G Thomas; Laulederkind, Stanley J F; Liu, Weisong; Nigam, Rajni; Petri, Victoria; Smith, Jennifer R; Tutaj, Marek; Wang, Shur-Jen; Worthey, Elizabeth; Dwinell, Melinda; Jacob, Howard

    2015-01-01

    The Rat Genome Database (RGD, http://rgd.mcw.edu) provides the most comprehensive data repository and informatics platform related to the laboratory rat, one of the most important model organisms for disease studies. RGD maintains and updates datasets for genomic elements such as genes, transcripts and increasingly in recent years, sequence variations, as well as map positions for multiple assemblies and sequence information. Functional annotations for genomic elements are curated from published literature, submitted by researchers and integrated from other public resources. Complementing the genomic data catalogs are those associated with phenotypes and disease, including strains, QTL and experimental phenotype measurements across hundreds of strains. Data are submitted by researchers, acquired through bulk data pipelines or curated from published literature. Innovative software tools provide users with an integrated platform to query, mine, display and analyze valuable genomic and phenomic datasets for discovery and enhancement of their own research. This update highlights recent developments that reflect an increasing focus on: (i) genomic variation, (ii) phenotypes and diseases, (iii) data related to the environment and experimental conditions and (iv) datasets and software tools that allow the user to explore and analyze the interactions among these and their impact on disease. PMID:25355511

  7. Quantification of retinal pigment epithelial phenotypic variation using laser scanning cytometry

    PubMed Central

    Fujikawa, A.; Oltjen, S.L.; Smit-McBride, Z.; Braunschweig, D.

    2010-01-01

    Purpose Quantifying phenotypic variation at the level of protein expression (variegation) within populations of retinal pigment epithelium (RPE) cells may be important in the study of pathologies associated with this variation. The lack of quantitative methods for examining single cells, however, and the variable presence of pigment and/or lipofuscin complicate this experimental goal. We have applied the technique of laser scanning cytometry (LSC) to paraffin sections of mouse and human eyes to evaluate the utility of LSC for these measurements. Methods Mouse eyes were perfusion fixed in 4% paraformaldehyde and embedded in paraffin. Postmortem human eyes were fixed and dissected to obtain a 9-mm punch, which was then embedded in paraffin. A laser scanning cytometer equipped with violet, argon, and helium-neon lasers and the detectors for blue, green, and long red were used to record the fluorescence of each individual cell at all three wavelengths. Raw data were recorded and processed using the WinCyte software. Individual nuclei were identified by the fluorescence of the 4’,6-diamidino-2-phenylindole (DAPI) nuclear counterstain. Next, RPE cells were uniquely identified in the green channel using an anti-retinal pigment epithelium-specific protein 65 kDa (anti-RPE65) monoclonal antibody with an Alexa Fluor 488-labeled secondary antibody. Mn-superoxide dismutase (MnSOD) was quantified in the long-red channel using an anti-MnSOD antibody and an Alexa Fluor 647-labeled secondary antibody. MnSOD+ and RPE65+ cells exhibited peaks in the plot of fluorescence intensity versus cell number, which could be characterized by the mean fluorescence intensity (MFI), the coefficient of variation (CV), and the percentage of total RPE cells that were also labeled for MnSOD. Results RPE cells can be uniquely identified in human and mouse paraffin sections by immunolabeling with anti-RPE65 antibody. A second antigen, such as MnSOD, can then be probed only within this set of RPE. Results are plotted primarily with the population frequency diagram, which can be subdivided into multiple regions. The data collected for each region include the MFI, the CV, and the number of cells that are immunolabeled in that region. Background interference from pigment or autofluorescent material can be successfully overcome by elevating the concentrations of fluorescent secondary antibodies. In the human and mouse eyes, age-related changes in MFI, CV, and percent RPE cells immunolabeled for MnSOD were observed. Conclusions The extent of the variability of gene expression in RPE cells at the protein level can be quantified by LSC. Relative changes in the MFI, the CV, and/or percentage of RPE cells double labeled for a second antigen quantify the changes observed. The analysis of these data also suggest whether the effects observed are related to local changes in transcription (alterations of CV) or major changes of protein expression (MFI), which are likely to be due to changes in the chromatin structure. The changes of these variables with age suggest that the observed age-related variegation is primarily due to changes in the chromatin structure in individual cells. PMID:20606706

  8. Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

    PubMed Central

    Derrien, Thomas; Axelsson, Erik; Rosengren Pielberg, Gerli; Sigurdsson, Snaevar; Fall, Tove; Seppälä, Eija H.; Hansen, Mark S. T.; Lawley, Cindy T.; Karlsson, Elinor K.; Bannasch, Danika; Vilà, Carles; Lohi, Hannes; Galibert, Francis; Fredholm, Merete; Häggström, Jens; Hedhammar, Åke; André, Catherine; Lindblad-Toh, Kerstin; Hitte, Christophe; Webster, Matthew T.

    2011-01-01

    The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease. PMID:22022279

  9. SELDI-TOF MS analysis of alkylphenol exposed Atlantic cod with phenotypic variation in gonadosomatic index.

    PubMed

    Nilsen, Mari Mæland; Meier, Sonnich; Andersen, Odd Ketil; Hjelle, Anne

    2011-11-01

    Proteomics is a new and promising approach to evaluate potential effects of pollution. In order to investigate if there is a direct link between the protein expression profiles obtained by the SELDI-TOF MS technology and effects observed at the organism level in fish, plasma samples from unexposed and 20 ppb alkylphenol exposed female Atlantic cod (Gadus morhua) with high phenotypic variation in gonadosomatic index (GSI) were analyzed by SELDI-TOF MS. Principle component analysis (PCA) showed that the major proteomic variation present in the dataset (i.e. 23.6%) could be significantly correlated to the individual variation in GSI, which indicates that SELDI-TOF MS data can reflect effects observed at higher levels of organization in fish. Further exploration of the other principal components revealed an additional proteomic pattern specific for the alkylphenol exposed females. Hence, this study supports the usefulness of SELDI-TOF MS as a proteomic tool in ecotoxicological research. PMID:21945013

  10. Inferring metabolic phenotypes from the exometabolome through a thermodynamic variational principle

    NASA Astrophysics Data System (ADS)

    De Martino, Daniele; Capuani, Fabrizio; De Martino, Andrea

    2014-11-01

    Networks of biochemical reactions, like cellular metabolic networks, are kept in non-equilibrium steady states by the exchange fluxes connecting them to the environment. In most cases, feasible flux configurations can be derived from minimal mass-balance assumptions upon prescribing in- and outtake fluxes. Here we consider the problem of inferring intracellular flux patterns from extracellular metabolite levels. Resorting to a thermodynamic out of equilibrium variational principle to describe the network at steady state, we show that the switch from fermentative to oxidative phenotypes in cells can be characterized in terms of the glucose, lactate, oxygen and carbon dioxide concentrations. Results obtained for an exactly solvable toy model are fully recovered for a large scale reconstruction of human catabolism. Finally we argue that, in spite of the many approximations involved in the theory, available data for several human cell types are well described by the predicted phenotypic map of the problem.

  11. Phenotypic variation of the Mexican duck (Anas platyrhynchos diazi) in Mexico

    USGS Publications Warehouse

    Scott, N.J., Jr.; Reynolds, R.P.

    1984-01-01

    A collection of 98 breeding Mexican Ducks (Anas platyrhynchos diazi) was made in Mexico from six areas between the United States border with Chihuahua and Lake Chapala, Jalisco, in order to study geographic variation. Plumage indices showed a relatively smooth clinal change from north to south; northern populations were most influenced by the Northern Mallard (A. platyrhynchos) phenotype. Measurements of total, wing, and culmen lengths and bill width were usually significantly larger in males at any one site, but showed no regular geographic trends. Hybridization between platyrhynchos and diazi phenotypes may or may not be increasing in the middle Rio Grande and Rio Conchos valleys; available data are insufficient to decide. A spring 1978 aerial census yielded an estimate of 55,500 diazi -like birds in Mexico. Populations of diazi appear to be as large as the available habitat allows; management should be directed towards increasing and stabilizing the nesting habitat; and the stability of the zone of intergradation should be investigated.

  12. A pleiotropic nonadditive model of variation in quantitative traits

    SciTech Connect

    Caballero, A.; Keightley, P.D. [Univ. of Edinburgh, Scotland (United Kingdom)

    1994-11-01

    A model of mutation-selection-drift balance incorporating pleiotropic and dominance effects of new mutations on quantitative traits and fitness is investigated and used to predict the amount and nature of genetic variation maintained in segregating populations. The model is based on recent information on the joint distribution of mutant effects on bristle traits and fitness in Drosophila melanogaster from experiments on the accumulation of spontaneous and P element-induced mutations. Mutants of large effect tend to be partially recessive while those with smaller effect are on average additive, but apparently with very variable gene action. The model is parameterized with two different sets of information derived from P element insertion and spontaneous mutation data, though the latter are not fully known. They differ in the number of mutations per generation which is assumed to affect the trait. Predictions of the variance maintained for bristle number assuming parameters derived from effects of P element insertions fit reasonably well with experimental observations. The equilibrium genetic variance is nearly independent of the degree of dominance of new mutations. Heritabilities of between 0.4 and 0.6 are predicted with population sizes from 10{sup 4} to 10{sup 6}, and most of the variance for the metric trait in segregating populations is due to a small proportion of mutations with neutral or nearly neutral effects on fitness and intermediate effects on the trait. Much of the genetic variance is contributed by recessive or partially recessive mutants, but only a small proportion of the genetic variance is dominance variance. If a model is assumed in which all mutation events have an effect on the quantitative trait, the majority of the genetic variance is contributed by deleterious mutations with tiny effects on the trait. If such a model is assumed for variability, the heritability is about 0.1, independent of the population size. 83 refs., 8 figs., 8 tabs.

  13. Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

    SciTech Connect

    Carneiro, Ana [Vanderbilt University; Airey, David [University of Tennessee Health Science Center, Memphis; Thompson, Brent [Vanderbilt University; Zhu, C [Vanderbilt University; Rinchik, Eugene M [ORNL; Lu, Lu [University of Tennessee Health Science Center, Memphis; Chesler, Elissa J [ORNL; Erikson, Keith [University of North Carolina; Blakely, Randy [Vanderbilt University

    2009-01-01

    The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GK variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.

  14. Quantitative phenotyping as an efficient means to estimate C-cell number in a knock-in mouse model of MEN2B.

    PubMed

    Cranston, Aaron; Howard, Louise; Howard, C Vyvyan

    2004-08-01

    Over the last two decades we have witnessed the generation of hundreds, if not thousands, of lines of genetically altered mice, large numbers of which are being produced in order to model human disease. Given that their creation is still rather technically demanding and labour intensive, the time taken analysing the resultant phenotypes should be such that the maximal amount of information can be gleaned efficiently in an unbiased manner so as to be as close to the 'true' value as possible. In an attempt to characterise a cell-specific phenotype in a genetically defined knock-in mouse model of multiple endocrine neoplasia type 2B (MEN2B) we used a modern, unbiased, stereological approach called the optical fractionator to estimate total cell number in 3-D space. By applying a sampling technique to tissue blocks in a systematic random uniform manner, we demonstrate that the total number of calcitonin-immunoreactive C-cells in the thyroid glands of littermate mice harbouring activating mutations in one or both alleles of ret does not vary significantly (p = 0.46) from an unbiased estimate of 23,000 in wild-type controls; likewise, neither does mean thyroid volume (p = 0.78) when estimated using Cavalieri's principle. We demonstrate that the variation associated with the quantitative phenotyping method is negligible. Using this efficient, unbiased stereological method our results provide new insights into cell number and positioning with consequences for both normal and disease states. In summary, this unbiased stereological technique is conceptually simple, can be applied efficiently, and is pertinent to quantitating a wide variety of cell phenotypes thereby bridging specialisation boundaries. We propose the adoption of this technique to mouse experimental geneticists and recommend its horizontal transmission across all fields within experimental biology. PMID:15517993

  15. Quantitative genomics of 30 complex phenotypes in Wagyu x Angus F? progeny.

    PubMed

    Zhang, Lifan; Michal, Jennifer J; O'Fallon, James V; Pan, Zengxiang; Gaskins, Charles T; Reeves, Jerry J; Busboom, Jan R; Zhou, Xiang; Ding, Bo; Dodson, Michael V; Jiang, Zhihua

    2012-01-01

    In the present study, a total of 91 genes involved in various pathways were investigated for their associations with six carcass traits and twenty-four fatty acid composition phenotypes in a Wagyu×Angus reference population, including 43 Wagyu bulls and their potential 791 F(1) progeny. Of the 182 SNPs evaluated, 102 SNPs that were in Hardy-Weinberg equilibrium with minor allele frequencies (MAF>0.15) were selected for parentage assignment and association studies with these quantitative traits. The parentage assignment revealed that 40 of 43 Wagyu sires produced over 96.71% of the calves in the population. Linkage disequilibrium analysis identified 75 of 102 SNPs derived from 54 genes as tagged SNPs. After Bonferroni correction, single-marker analysis revealed a total of 113 significant associations between 44 genes and 29 phenotypes (adjusted P<0.05). Multiple-marker analysis confirmed single-gene associations for 10 traits, but revealed two-gene networks for 9 traits and three-gene networks for 8 traits. Particularly, we observed that TNF (tumor necrosis factor) gene is significantly associated with both beef marbling score (P=0.0016) and palmitic acid (C16:0) (P=0.0043), RCAN1 (regulator of calcineurin 1) with rib-eye area (P=0.0103), ASB3 (ankyrin repeat and SOCS box-containing 3) with backfat (P=0.0392), ABCA1 (ATP-binding cassette A1) with both palmitic acid (C16:0) (P=0.0025) and oleic acid (C18:1n9) (P=0.0114), SLC27A1(solute carrier family 27 A1) with oleic acid (C18:1n9) (P=0.0155), CRH (corticotropin releasing hormone) with both linolenic acid (OMEGA-3) (P=0.0200) and OMEGA 6:3 RATIO (P=0.0054), SLC27A2 (solute carrier family 27 A2) with both linoleic acid (OMEGA-6) (P=0.0121) and FAT (P=0.0333), GNG3 (guanine nucleotide binding protein gamma 3 with desaturase 9 (P=0.0115), and EFEMP1 (EGF containing fibulin-like extracellular matrix protein 1), PLTP (phospholipid transfer protein) and DSEL (dermatan sulfate epimerase-like) with conjugated linoleic acid (P=0.0042-0.0044), respectively, in the Wagyu x Angus F(1) population. In addition, we observed an interesting phenomenon that crossbreeding of different breeds might change gene actions to dominant and overdominant modes, thus explaining the origin of heterosis. The present study confirmed that these important families or pathway-based genes are useful targets for improving meat quality traits and healthful beef products in cattle. PMID:22745575

  16. Quantitative Genomics of 30 Complex Phenotypes in Wagyu x Angus F1 Progeny

    PubMed Central

    Zhang, Lifan; Michal, Jennifer J.; O'Fallon, James V.; Pan, Zengxiang; Gaskins, Charles T.; Reeves, Jerry J.; Busboom, Jan R.; Zhou, Xiang; Ding, Bo; Dodson, Michael V.; Jiang, Zhihua

    2012-01-01

    In the present study, a total of 91 genes involved in various pathways were investigated for their associations with six carcass traits and twenty-four fatty acid composition phenotypes in a Wagyu×Angus reference population, including 43 Wagyu bulls and their potential 791 F1 progeny. Of the 182 SNPs evaluated, 102 SNPs that were in Hardy-Weinberg equilibrium with minor allele frequencies (MAF>0.15) were selected for parentage assignment and association studies with these quantitative traits. The parentage assignment revealed that 40 of 43 Wagyu sires produced over 96.71% of the calves in the population. Linkage disequilibrium analysis identified 75 of 102 SNPs derived from 54 genes as tagged SNPs. After Bonferroni correction, single-marker analysis revealed a total of 113 significant associations between 44 genes and 29 phenotypes (adjusted P<0.05). Multiple-marker analysis confirmed single-gene associations for 10 traits, but revealed two-gene networks for 9 traits and three-gene networks for 8 traits. Particularly, we observed that TNF (tumor necrosis factor) gene is significantly associated with both beef marbling score (P=0.0016) and palmitic acid (C16:0) (P=0.0043), RCAN1 (regulator of calcineurin 1) with rib-eye area (P=0.0103), ASB3 (ankyrin repeat and SOCS box-containing 3) with backfat (P=0.0392), ABCA1 (ATP-binding cassette A1) with both palmitic acid (C16:0) (P=0.0025) and oleic acid (C18:1n9) (P=0.0114), SLC27A1(solute carrier family 27 A1) with oleic acid (C18:1n9) (P=0.0155), CRH (corticotropin releasing hormone) with both linolenic acid (OMEGA-3) (P=0.0200) and OMEGA 6:3 RATIO (P=0.0054), SLC27A2 (solute carrier family 27 A2) with both linoleic acid (OMEGA-6) (P=0.0121) and FAT (P=0.0333), GNG3 (guanine nucleotide binding protein gamma 3 with desaturase 9 (P=0.0115), and EFEMP1 (EGF containing fibulin-like extracellular matrix protein 1), PLTP (phospholipid transfer protein) and DSEL (dermatan sulfate epimerase-like) with conjugated linoleic acid (P=0.0042-0.0044), respectively, in the Wagyu x Angus F1 population. In addition, we observed an interesting phenomenon that crossbreeding of different breeds might change gene actions to dominant and overdominant modes, thus explaining the origin of heterosis. The present study confirmed that these important families or pathway-based genes are useful targets for improving meat quality traits and healthful beef products in cattle. PMID:22745575

  17. International Association for Ecology Relationship of Phenotypic and Genetic Variation in Plantago lanceolata to Disease Caused by

    E-print Network

    Antonovics, Janis

    COiOgla ? Springer-Verlag1984 Relationshipof phenotypicand genetic variation in Plantago lanceolata to disease caused a population of Plantago lanceolata L. (the ribwort plantain) in which approximately 10% of the floweringInternational Association for Ecology Relationship of Phenotypic and Genetic Variation in Plantago

  18. Behavioral variation in pelvic phenotypes of brook stickleback, Culaea inconstans , in response to predation by northern pike, Esox lucius

    Microsoft Academic Search

    James D. Reist

    1983-01-01

    Populations ofCulaea inconstans, from Alberta and Saskatchewan, Canada exhibit phenotypic variation in expression of the pelvic skeleton and associated spines, from complete presence (with) through intermediate forms to complete absence (without). Such variation influences predation byEsox lucius which prefer the least spiny prey. Behavioral differences were investigated before and during pike predation. These differences may be associated either with the

  19. Phenotypic variation in seedlings of a “keystone” tree species ( Quercus douglasii ): the interactive effects of acorn source and competitive environment

    Microsoft Academic Search

    K. J. Rice; D. R. Gordon; J. L. Hardison; J. M. Welker

    1993-01-01

    Blue oak (Quercus douglasii) is a deciduous tree species endemic to California that currently exhibits poor seedling survival to sapling age classes. We used common garden techniques to examine how genetic variation at regional and local scales affected phenotypic expression in traits affecting oak seedling growth and survival. Between-population variation was examined for seedlings grown from acorns collected from a

  20. Immunological variation between inbred laboratory mouse strains: points to consider in phenotyping genetically immunomodified mice.

    PubMed

    Sellers, R S; Clifford, C B; Treuting, P M; Brayton, C

    2012-01-01

    Inbred laboratory mouse strains are highly divergent in their immune response patterns as a result of genetic mutations and polymorphisms. The generation of genetically engineered mice (GEM) has, in the past, used embryonic stem (ES) cells for gene targeting from various 129 substrains followed by backcrossing into more fecund mouse strains. Although common inbred mice are considered "immune competent," many have variations in their immune system-some of which have been described-that may affect the phenotype. Recognition of these immune variations among commonly used inbred mouse strains is essential for the accurate interpretation of expected phenotypes or those that may arise unexpectedly. In GEM developed to study specific components of the immune system, accurate evaluation of immune responses must take into consideration not only the gene of interest but also how the background strain and microbial milieu contribute to the manifestation of findings in these mice. This article discusses points to consider regarding immunological differences between the common inbred laboratory mouse strains, particularly in their use as background strains in GEM. PMID:22135019

  1. 3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture

    PubMed Central

    Topp, Christopher N.; Iyer-Pascuzzi, Anjali S.; Anderson, Jill T.; Lee, Cheng-Ruei; Zurek, Paul R.; Symonova, Olga; Zheng, Ying; Bucksch, Alexander; Mileyko, Yuriy; Galkovskyi, Taras; Moore, Brad T.; Harer, John; Edelsbrunner, Herbert; Mitchell-Olds, Thomas; Weitz, Joshua S.; Benfey, Philip N.

    2013-01-01

    Identification of genes that control root system architecture in crop plants requires innovations that enable high-throughput and accurate measurements of root system architecture through time. We demonstrate the ability of a semiautomated 3D in vivo imaging and digital phenotyping pipeline to interrogate the quantitative genetic basis of root system growth in a rice biparental mapping population, Bala × Azucena. We phenotyped >1,400 3D root models and >57,000 2D images for a suite of 25 traits that quantified the distribution, shape, extent of exploration, and the intrinsic size of root networks at days 12, 14, and 16 of growth in a gellan gum medium. From these data we identified 89 quantitative trait loci, some of which correspond to those found previously in soil-grown plants, and provide evidence for genetic tradeoffs in root growth allocations, such as between the extent and thoroughness of exploration. We also developed a multivariate method for generating and mapping central root architecture phenotypes and used it to identify five major quantitative trait loci (r2 = 24–37%), two of which were not identified by our univariate analysis. Our imaging and analytical platform provides a means to identify genes with high potential for improving root traits and agronomic qualities of crops. PMID:23580618

  2. Molecular genetics of growth and development in Populus (Salicaceae). V. Mapping quantitative trait loci affecting leaf variation

    SciTech Connect

    Wu, R.; Bradshaw, H.D. Jr.; Stettler, R.F. [Univ. of Washington, Seattle, WA (United States)

    1997-02-01

    The genetic variation of leaf morphology and development was studied in the 2-yr-old replicated plantation of an interspecific hybrid pedigree of Populus trichocarpa T. & G. and P. deltoides Marsh. via both molecular and quantitative genetic methods. Leaf traits chosen showed pronounced differences between the original parents, including leaf size, shape, orientation, color, structure, petiole size, and petiole cross section. In the F{sub 2} generation, leaf traits were all significantly different among genotypes, but with significant effects due to genotype X crown-position interaction. Variation in leaf pigmentation, petiole length, and petiole length proportion appeared to be under the control of few quantitative trait loci (QTLs). More QTLs were associated with single leaf area, leaf shape, lamina angle, abaxial color, and petiole flatness, and in these traits the number of QTLs varied among crown positions. In general the estimates of QTL numbers from Wright`s biometric method were close to those derived from molecular markers. For those traits with few underlying QTLs, a single marker interval could explain from 30-60% of the observed phenotypic variance. For multigenic traits, certain markers contributed more substantially to the observed variation than others. Genetic cluster analysis showed developmentally related traits to be more strongly associated with each other than with unrelated traits. This finding was also supported by the QTL mapping. For example, the same chromosomal segment of linkage group L seemed to account for 20% of the phenotypic variation of all dimension-related traits, leaf size, petiole length, and midrib angle. In both traits, the P. deltoides alleles had positive effects and were dominant to the P. trichocarpa alleles. Similar relationships were also found for lamina angle, abaxial greenness, and petiole flatness. 72 refs., 3 figs., 2 tabs.

  3. Genotypic and phenotypic variation as stress adaptations in temperate tree species: a review of several case studies.

    PubMed

    Abrams, Marc D.

    1994-01-01

    Species that occupy large geographic ranges or a variety of habitats within a limited area deal with contrasting environmental conditions by genotypic and phenotypic variation. My students and I have studied these forms of ecophysiological variation in temperate tree species in eastern North America by means of a series of field and greenhouse experiments, including controlled studies with Cercis canadensis L., Fraxinus pennsylvanica Marsh., Acer rubrum L., Prunus serotina Ehrh. and Quercus rubra L., in relation to drought stress. These studies have included measurements of gas exchange, tissue water relations and leaf morphology, and have identified genotypic variation at the biome and individual community levels. Xeric genotypes generally had higher net photosynthesis and leaf conductance and lower osmotic and water potentials at incipient wilting than mesic genotypes during drought. Xeric genotypes also produced leaves with greater thickness, leaf mass per area and stomatal density and smaller area than the mesic genotypes, suggesting general coordination among leaf morphology, gas exchange and tissue water relations. Leaf phenotypic plasticity to different light environments occurred in virtually every study species, which represented a wide array of ecological tolerances. In a study of interactions of genotypes with environment, shade plants, but not sun plants, exhibited osmotic adjustment during drought and shade plants had smaller reductions in photosynthesis with decreasing leaf water potential. In that study, sun, but not shade, plants had significant genotypic differences in leaf structure, but with certain variables phenotypic variation exceeded genotype variation. Thus, genotypic variation was not expressed in all phenotypes, and phenotypes responded differentially to stress. Overall, these studies indicate the importance of genotypic and phenotypic variation as stress adaptations in temperate tree species among both distant and nearby sites of contrasting environmental conditions. PMID:14967652

  4. Sex-specific phenotypic selection and geographic variation in gender divergence in a gynodioecious shrub.

    PubMed

    Castilla, A R; Alonso, C; Herrera, C M

    2015-01-01

    In sexually polymorphic plant species the extent of gender divergence in floral morphology and phenology may be influenced by gender-specific selection patterns imposed by pollinators, which may change geographically. Distribution margins are areas where changes in the pollinator fauna, and thus variation in gender divergence of floral traits, are expected. We tested for pollination-driven geographic variation in the gender divergence in floral and phenological traits in the gynodioecious shrub Daphne laureola, in core and marginal areas differing in the identity of the main pollinator. Pollinators selected for longer corolla tubes in hermaphrodite individuals only in core populations, which in turn recorded higher fruit set. Consistent with these phenotypic selection patterns, gender divergence in flower corolla length was higher in core populations. Moreover, pollinators selected towards delayed flowering on hermaphrodite individuals only in marginal populations, where the two sexes differed more in flowering time. Our results support that a shift in main pollinators is able to contribute to geographic variation in the gender divergence of sexually polymorphic plant species. PMID:24841933

  5. Maintenance of clinal variation for shell colour phenotype in the flat periwinkle Littorina obtusata.

    PubMed

    Phifer-Rixey, M; Heckman, M; Trussell, G C; Schmidt, P S

    2008-07-01

    Clines can signal spatially varying selection and therefore have long been used to investigate the role of environmental heterogeneity in maintaining genetic variation. However, clinal patterns alone are not sufficient to reject neutrality or to establish the mechanism of selection. Indirect, inferential methods can be used to address neutrality and mechanism, but fully understanding the adaptive significance of clinal variation ultimately requires a direct approach. Ecological model systems such as the rocky intertidal provide a useful context for direct experimentation and can serve as a complement to studies in more traditional genetic model systems. In this study, we use indirect and direct approaches to investigate the role of environmental heterogeneity in the maintenance of shell colour polymorphism in the flat periwinkle snail, Littorina obtusata. We document replicated clines in shell colour morph frequencies over thermal gradients at two spatial scales, contrasting with patterns at previously reported microsatellite loci. In addition, experimental results demonstrate that that shell colour has predictable effects on shell temperature and that these differences in temperature, in turn, coincide with patterns of survivorship under episodic thermal stress. Direct manipulation of shell colour revealed that shell colour, and not a correlated character, was the target of selection. Our study provides evidence that spatially varying selection via thermal regime contributes to the maintenance of shell colour phenotype variation in L. obtusata in the sampled areas of the Gulf of Maine. PMID:18507701

  6. Cone and seed trait variation in whitebark pine (Pinus albicaulis; Pinaceae) and the potential for phenotypic selection.

    PubMed

    Garcia, Roberto; Siepielski, Adam M; Benkman, Craig W

    2009-05-01

    Phenotypic variation among individuals is necessary for natural selection to operate and is therefore essential for adaptive evolution. However, extensive variation within individuals can mask variation among individuals and weaken the potential for selection. Here we quantify variation among and within individuals in female cone and seed traits of whitebark pine (Pinus albicaulis). In many plants, the production of numerous reproductive structures creates the potential for considerable variation within a plant, but these same traits should also undergo strong selection because of their direct link to plant fitness. We found about twice as much variation among individuals (overall mean = 65.3 ± 4.5% SE) than within individuals (overall mean = 34.7 ± 4.5%). One only needs to sample three to five cones per tree to accurately assess variation among trees in most cone and seed traits. The ease at which trees can be assessed helps account for the strong and consistent patterns of phenotypic selection exerted by seed predators and dispersers of whitebark pine and many other conifers. In contrast, the few traits where variation within trees equaled or exceeded that among trees underwent weak if any phenotypic selection. PMID:21628255

  7. Phenotypic flexibility in passerine birds: seasonal variation in fuel storage, mobilization and transport.

    PubMed

    Liknes, Eric T; Guglielmo, Christopher G; Swanson, David L

    2014-08-01

    Winter acclimatization in small birds living in cold climates produces a winter phenotype characterized by upregulation of metabolic rates to meet enhanced thermoregulatory demands. We measured several key aspects of fuel storage, mobilization and transport in summer and winter to determine whether black-capped chickadees (Poecile atricapillus), white-breasted nuthatches (Sitta carolinensis), and house sparrows (Passer domesticus) seasonally modulate these attributes to meet enhanced winter thermoregulatory demands. In addition, we exposed birds to thermoneutral (control) and severe cold exposure treatments to determine whether acute cold exposure influenced fuel storage, mobilization or transport. Carcass lipid mass and pectoralis intramuscular lipid did not vary significantly between seasons or temperature treatments for any of the study species. Muscle glycogen varied significantly seasonally only for chickadee supracoracoideus and leg muscles, and did not vary among warm or cold treatments for any species. Pectoralis fatty acid binding protein (FABPc) was significantly elevated in winter for chickadees and nuthatches, but not for sparrows. Plasma metabolites showed little consistent variation in response to season or acute cold exposure. Thus, fuel storage and mobilization do not appear to be major targets of adjustment associated with seasonal metabolic flexibility in these species, but modulation of intracellular lipid transport by FABPc may be an important contributor to seasonal phenotypes in some species of small birds. PMID:24704472

  8. PhenoMiner: a quantitative phenotype database for the laboratory rat, Rattus norvegicus. Application in hypertension and renal disease

    PubMed Central

    Wang, Shur-Jen; Laulederkind, Stanley J. F.; Hayman, G. Thomas; Petri, Victoria; Liu, Weisong; Smith, Jennifer R.; Nigam, Rajni; Dwinell, Melinda R.; Shimoyama, Mary

    2015-01-01

    Rats have been used extensively as animal models to study physiological and pathological processes involved in human diseases. Numerous rat strains have been selectively bred for certain biological traits related to specific medical interests. Recently, the Rat Genome Database (http://rgd.mcw.edu) has initiated the PhenoMiner project to integrate quantitative phenotype data from the PhysGen Program for Genomic Applications and the National BioResource Project in Japan as well as manual annotations from biomedical literature. PhenoMiner, the search engine for these integrated phenotype data, facilitates mining of data sets across studies by searching the database with a combination of terms from four different ontologies/vocabularies (Rat Strain Ontology, Clinical Measurement Ontology, Measurement Method Ontology and Experimental Condition Ontology). In this study, salt-induced hypertension was used as a model to retrieve blood pressure records of Brown Norway, Fawn-Hooded Hypertensive (FHH) and Dahl salt-sensitive (SS) rat strains. The records from these three strains served as a basis for comparing records from consomic/congenic/mutant offspring derived from them. We examined the cardiovascular and renal phenotypes of consomics derived from FHH and SS, and of SS congenics and mutants. The availability of quantitative records across laboratories in one database, such as these provided by PhenoMiner, can empower researchers to make the best use of publicly available data. Database URL: http://rgd.mcw.edu PMID:25632109

  9. A non-parametric test to detect quantitative trait loci where the phenotypic distribution differs by genotypes

    PubMed Central

    Aschard, Hugues; Zaitlen, Noah; Tamimi, Rulla M.; Lindström, Sara; Kraft, Peter

    2014-01-01

    Searching for genetic variants involved in gene-gene and gene-environment interactions in large scale data raises multiple methodological issues. Many existing methods have focused on the problem of dimensionality, trying to explore the largest number of combinations between risk factors while considering simple interaction models. Despite evidence demonstrating the efficacy of these methods in simulated data, their application in real data has been unsuccessful so far. The classical test of a linear marginal genetic effect has been widely used for agnostic genome-wide association studies, with the underlying idea that most variants involved in interactions might display marginal effect on the phenotypic mean. While this approach may allow for the identification of genetic variants involved in interactions in many scenarios, the linear marginal effects of some causal alleles on the phenotypic mean might not be always detectable at genome-wide significance level. We introduce in this study a general association test for quantitative trait loci that compare the distributions of phenotypic values by genotypic classes as opposed to most standard tests that compare phenotypic means by genotypic classes. Using simulation we show that in presence of an interaction, this approach can be more powerful than the standard test of the linear marginal exposures. We demonstrate the potential utility of our method on real data by analyzing mammographic density genome-wide data from the Nurses’ Health Study. PMID:23512279

  10. Temporal patterns of genetic and phenotypic variation in the epidemiologically important drone fly, Eristalis tenax.

    PubMed

    Francuski, Lj; Mati?, I; Ludoški, J; Milankov, V

    2011-06-01

    Eristalis tenax L. (Diptera: Syrphidae) is commonly known as the drone fly (adult) or rat-tailed maggot (immature). Both adults and immature stages are identified as potential mechanical vectors of mycobacterial pathogens, and early-stage maggots cause accidental myiasis. We compared four samples from Mount Fruška Gora, Serbia, with the aim of obtaining insights into the temporal variations and sexual dimorphism in the species. This integrative approach was based on allozyme loci, morphometric wing parameters (shape and size) and abdominal colour patterns. Consistent sexual dimorphism was observed, indicating that male specimens had lighter abdomens and smaller and narrower wings than females. The distribution of genetic diversity at polymorphic loci indicated genetic divergence among collection dates. Landmark-based geometric morphometrics revealed, contrary to the lack of divergence in wing size, significant wing shape variation throughout the year. In addition, temporal changes in the frequencies of the abdominal patterns observed are likely to relate to the biology of the species and ecological factors in the locality. Hence, the present study expands our knowledge of the genetic diversity and phenotypic plasticity of E. tenax. The quantification of such variability represents a step towards the evaluation of the adaptive potential of this species of medical and epidemiological importance. PMID:21414022

  11. Phenotypic variation and vulnerability to predation in juvenile bluegill sunfish (Lepomis macrochirus)

    USGS Publications Warehouse

    Chipps, S.R.; Dunbar, J.A.; Wahl, David H.

    2004-01-01

    Bluegill sunfish (Lepomis macrochirus) are known to diversify into two forms specialized for foraging on either limnetic or littoral prey. Because juvenile bluegills seek vegetative cover in the presence of largemouth bass (Micropterus salmoides) predators, natural selection should favor the littoral body design at size ranges most vulnerable to predation. Yet within bluegill populations, both limnetic and littoral forms occur where vegetation and predators are present. While adaptive for foraging in different environments, does habitat-linked phenotypic variation also influence predator evasiveness for juvenile bluegills? We evaluate this question by quantifying susceptibility to predation for two groups of morphologically distinct bluegills; a limnetic form characteristic of bluegills inhabiting open water areas (limnetic bluegill) and a littoral form characteristic of bluegills inhabiting dense vegetation (littoral bluegill). In a series of predation trials, we found that bluegill behaviors differed in open water habitat but not in simulated vegetation. In open water habitat, limnetic bluegills formed more dense shoaling aggregations, maintained a larger distance from the predator, and required longer amounts of time to capture than littoral bluegill. When provided with simulated vegetation, largemouth bass spent longer amounts of time pursuing littoral bluegill and captured significantly fewer littoral bluegills than limnetic fish. Hence, morphological and behavioral variation in bluegills was linked to differential susceptibility to predation in open water and vegetated environments. Combined with previous studies, these findings show that morphological and behavioral adaptations enhance both foraging performance and predator evasiveness in different lake habitats.

  12. Molecular evolution and quantitative variation for chemosensory behaviour in the nematode genus Caenorhabditis

    Microsoft Academic Search

    R. Jovelin; B. C. Ajie; P. C. Phillips

    2003-01-01

    Caenorhabditis elegans is a model organism in biology, yet despite the tremendous infor- mation generated from genetic, genomic and functional analyses, C. elegans has rarely been used to address questions in ecological genetics. Here, we analyse genetic variation for chemosensory behaviour, an ecologically important trait that is also genetically well char- acterized, at both the phenotypic and molecular levels within

  13. PLANT PHENOTYPIC VARIATION OF TWO HALF SIB FAMILIES OF FEIJOA (Acca sellowiana Berg.) FROM AN ORCHARD IN SÃO JOAQUIM, SC

    Microsoft Academic Search

    JULIANA DEGENHARDT; JEAN-PIERRE DUCROQUET; MIGUEL PEDRO GUERRA; RUBENS ONOFRE NODARI

    2005-01-01

    Feijoa (Acca sellowiana Berg.) is a native Myrtaceae of the Brazilian Southern plateau with secondary dispersion in Uruguay and its fruit has a unique flavor. Plants of a commercial orchard of this species originated by two half-sib families (FMI1 and FMI2) were evaluated, with the objective to characterize the phenotypic variation of several traits. The means (±standard deviation) of the

  14. Reevaluation of several taxa of Chinese lagomorphs (Mammalia: Lagomorpha) described on the basis of pelage phenotype variation

    Microsoft Academic Search

    Deyan Ge; Andrey A. Lissovsky; Lin Xia; Cheng Cheng; Andrew T. Smith; Yang Qisen

    Melanism is a common phenomenon in the animal kingdom. While the occurrence of melanism in lagomorphs has been less studied, this phenomenon has led to systematic confusion among different forms of pikas (Ochotona) and hares (Lepus). Within Ochotona, the Pianma black pika (O. nigritia) was established primarily based on its pelage phenotype variation compared with the sympatric Forrest's pika (O.

  15. Non-genetic phenotypic variation within and among individuals is a pervasive theme in physiology, ecology and

    E-print Network

    Saltzman, Wendy

    Non-genetic phenotypic variation within and among individuals is a pervasive theme in physiology, ecology and evolutionary biology. A familiar example is comparative physiology's long and productive. The ecological and evolutionary relevance of environmental influences on physiological traits (as well

  16. Identification of quantitative genetic components of fitness variation in farmed, hybrid and native salmon in the wild.

    PubMed

    Besnier, F; Glover, K A; Lien, S; Kent, M; Hansen, M M; Shen, X; Skaala, Ø

    2015-07-01

    Feral animals represent an important problem in many ecosystems due to interbreeding with wild conspecifics. Hybrid offspring from wild and domestic parents are often less adapted to local environment and ultimately, can reduce the fitness of the native population. This problem is an important concern in Norway, where each year, hundreds of thousands of farm Atlantic salmon escape from fish farms. Feral fish outnumber wild populations, leading to a possible loss of local adaptive genetic variation and erosion of genetic structure in wild populations. Studying the genetic factors underlying relative performance between wild and domesticated conspecific can help to better understand how domestication modifies the genetic background of populations, and how it may alter their ability to adapt to the natural environment. Here, based upon a large-scale release of wild, farm and wild x farm salmon crosses into a natural river system, a genome-wide quantitative trait locus (QTL) scan was performed on the offspring of 50 full-sib families, for traits related to fitness (length, weight, condition factor and survival). Six QTLs were detected as significant contributors to the phenotypic variation of the first three traits, explaining collectively between 9.8 and 14.8% of the phenotypic variation. The seventh QTL had a significant contribution to the variation in survival, and is regarded as a key factor to understand the fitness variability observed among salmon in the river. Interestingly, strong allelic correlation within one of the QTL regions in farmed salmon might reflect a recent selective sweep due to artificial selection. PMID:26059968

  17. Design of part family robust-to-production plan variations based on quantitative manufacturability evaluation

    E-print Network

    Saitou, Kazuhiro "Kazu"

    , a method is proposed to design product families that are robust to production plan variations, basedDesign of part family robust-to-production plan variations based on quantitative manufacturability evaluation Byungwoo Lee, Kazuhiro Saitou Abstract This paper presents a systematic method for designing part

  18. Genotype-Phenotype-Mapping and Neutral Variation - A Case Study in Genetic Programming

    Microsoft Academic Search

    Wolfgang Banzhaf

    1994-01-01

    . We propose the application of a genotype-phenotype mappingto the solution of constrained optimization problems. The methodconsists of strictly separating the search space of genotypes from the solutionspace of phenotypes. A mapping from genotypes into phenotypesprovides for the appropriate expression of information represented bythe genotypes. The mapping is constructed as to guarantee feasibilityof phenotypic solutions for the problem under study.

  19. J Allergy Clin Immunol. Author manuscript Interrelationships of quantitative asthma-related phenotypes in the

    E-print Network

    Paris-Sud XI, Université de

    J Allergy Clin Immunol. Author manuscript Page /1 9 Interrelationships of quantitative asthma the interrelationships of quantitative asthma-related traits. Objective To study the interrelationships of allergy). Results Allergy parameters were significantly higher in asthmatic cases than in controls for children

  20. Using machine vision to analyze and classify Caenorhabditis elegans behavioral phenotypes quantitatively

    E-print Network

    Cosman, Pamela C.

    as uncoordinated (Unc) mutants, have facilitated the genetic dissection of many important aspects of nervous system, to identify genes whose specific behavioral phenotypes reflect a specific role in nervous system function the context of an intact nervous system. The nematode C. elegans has powerful genetics, a well

  1. A theory of developmental change in quantitative phenotypes applied to cognitive development

    Microsoft Academic Search

    L. J. Eaves; J. Long; A. C. Heath

    1986-01-01

    A model is presented for the changes in familial resemblance as a function of age. The model allows for separate developmental components of genetic and environmental effects and for the influence of earlier phenotypic values on current measurements. Genetic and environmental effects may be specific to occasions or constant over time. Expected covariances are derived within individuals and between relatives

  2. The Developmental Basis of Quantitative Craniofacial Variation in Humans and Mice.

    PubMed

    Martínez-Abadías, Neus; Mitteroecker, Philipp; Parsons, Trish E; Esparza, Mireia; Sjøvold, Torstein; Rolian, Campbell; Richtsmeier, Joan T; Hallgrímsson, Benedikt

    2012-12-01

    The human skull is a complex and highly integrated structure that has long held the fascination of anthropologists and evolutionary biologists. Recent studies of the genetics of craniofacial variation reveal a very complex and multifactorial picture. These findings contrast with older ideas that posit much simpler developmental bases for variation in cranial morphology such as the growth of the brain or the growth of the chondrocranium relative to the dermatocranium. Such processes have been shown to have major effects on cranial morphology in mice. It is not known, however, whether they are relevant to explaining normal phenotypic variation in humans. To answer this question, we obtained vectors of shape change from mutant mouse models in which the developmental basis for the craniofacial phenotype is known to varying degrees, and compared these to a homologous dataset constructed from human crania obtained from a single population with a known genealogy. Our results show that the shape vectors associated with perturbations to chondrocranial growth, brain growth, and body size in mice do largely correspond to axes of covariation in humans. This finding supports the view that the developmental basis for craniofacial variation funnels down to a relatively small number of key developmental processes that are similar across mice and humans. Understanding these processes and how they influence craniofacial shape provides fundamental insights into the developmental basis for evolutionary change in the human skull as well as the developmental-genetic basis for normal phenotypic variation in craniofacial form. PMID:23226904

  3. Host and Bacterial Phenotype Variation in Adhesion of Streptococcus mutans to Matched Human Hosts

    PubMed Central

    Esberg, Anders; Löfgren-Burström, Anna; Öhman, Ulla

    2012-01-01

    The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r2 = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B1, and B2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B1 and B2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously. PMID:22927045

  4. A Quantitative Investigation of Stakeholder Variation in Training Program Evaluation.

    ERIC Educational Resources Information Center

    Michalski, Greg V.

    A survey was conducted to investigate variation in stakeholder perceptions of training results and evaluation within the context of a high-technology product development firm (the case organization). A scannable questionnaire survey booklet was developed and scanned data were exported and analyzed. Based on an achieved sample of 280 (70% response…

  5. Facial Phenotyping by Quantitative Photography Reflects Craniofacial Morphology Measured on Magnetic Resonance Imaging in Icelandic Sleep Apnea Patients

    PubMed Central

    Sutherland, Kate; Schwab, Richard J.; Maislin, Greg; Lee, Richard W.W.; Benedikstdsottir, Bryndis; Pack, Allan I.; Gislason, Thorarinn; Juliusson, Sigurdur; Cistulli, Peter A.

    2014-01-01

    Study Objectives: (1) To determine whether facial phenotype, measured by quantitative photography, relates to underlying craniofacial obstructive sleep apnea (OSA) risk factors, measured with magnetic resonance imaging (MRI); (2) To assess whether these associations are independent of body size and obesity. Design: Cross-sectional cohort. Setting: Landspitali, The National University Hospital, Iceland. Participants: One hundred forty patients (87.1% male) from the Icelandic Sleep Apnea Cohort who had both calibrated frontal and profile craniofacial photographs and upper airway MRI. Mean ± standard deviation age 56.1 ± 10.4 y, body mass index 33.5 ± 5.05 kg/m2, with on-average severe OSA (apnea-hypopnea index 45.4 ± 19.7 h-1). Interventions: N/A. Measurements and Results: Relationships between surface facial dimensions (photos) and facial bony dimensions and upper airway soft-tissue volumes (MRI) was assessed using canonical correlation analysis. Photo and MRI craniofacial datasets related in four significant canonical correlations, primarily driven by measurements of (1) maxillary-mandibular relationship (r = 0.8, P < 0.0001), (2) lower face height (r = 0.76, P < 0.0001), (3) mandibular length (r = 0.67, P < 0.0001), and (4) tongue volume (r = 0.52, P = 0.01). Correlations 1, 2, and 3 were unchanged when controlled for weight and neck and waist circumference. However, tongue volume was no longer significant, suggesting facial dimensions relate to tongue volume as a result of obesity. Conclusions: Significant associations were found between craniofacial variable sets from facial photography and MRI. This study confirms that facial photographic phenotype reflects underlying aspects of craniofacial skeletal abnormalities associated with OSA. Therefore, facial photographic phenotyping may be a useful tool to assess intermediate phenotypes for OSA, particularly in large-scale studies. Citation: Sutherland K, Schwab RJ, Maislin G, Lee RW, Benedikstdsottir B, Pack AI, Gislason T, Juliusson S, Cistulli PA. Facial phenotyping by quantitative photography reflects craniofacial morphology measured on magnetic resonance imaging in icelandic sleep apnea patients. SLEEP 2014;37(5):959-968. PMID:24790275

  6. Phenotypic variation in metamorphosis and paedomorphosis in the salamander Ambystoma talpoideum

    SciTech Connect

    Semlitsch, R.D.; Gibbons, J.W.

    1985-08-01

    Phenotypic variation in metamorphosis and paedomorphosis in the salamander Ambystoma talpoideum was examined to determine its environmental or genetic basis. Eight artificial ponds were maintained, four at each of two environmental treatments: constant water level, to simulate fish-free permanent breeding ponds, and gradual drying out, to simulate temporary breeding ponds. Two populations of salamanders were used, derived from two breeding ponds having different frequencies of paedomorphosis. The water level in the drying treatment was lowered during the last 10 wk of the experimental period with no apparent differences in water chemistry parameters between treatments and only a slight change in water temperature during the last 2 wk. The effects of water level were potentially confounded by those of water temperature, density of larvae, and amount food. Population differences in the frequency of metamorphosis and paedomorphosis could potentially represent genetic differences resulting from the different selective regimes that individuals encounter in breeding ponds varying in drying frequency. 35 references, 3 figures, 4 tables.

  7. Genomic Analysis of Natural Selection and Phenotypic Variation in High-Altitude Mongolians

    PubMed Central

    Watkins, W. Scott; Witherspoon, David J.; Wu, Wilfred; Qin, Ga; Huff, Chad D.; Jorde, Lynn B.; Ge, Ri-Li

    2013-01-01

    Deedu (DU) Mongolians, who migrated from the Mongolian steppes to the Qinghai-Tibetan Plateau approximately 500 years ago, are challenged by environmental conditions similar to native Tibetan highlanders. Identification of adaptive genetic factors in this population could provide insight into coordinated physiological responses to this environment. Here we examine genomic and phenotypic variation in this unique population and present the first complete analysis of a Mongolian whole-genome sequence. High-density SNP array data demonstrate that DU Mongolians share genetic ancestry with other Mongolian as well as Tibetan populations, specifically in genomic regions related with adaptation to high altitude. Several selection candidate genes identified in DU Mongolians are shared with other Asian groups (e.g., EDAR), neighboring Tibetan populations (including high-altitude candidates EPAS1, PKLR, and CYP2E1), as well as genes previously hypothesized to be associated with metabolic adaptation (e.g., PPARG). Hemoglobin concentration, a trait associated with high-altitude adaptation in Tibetans, is at an intermediate level in DU Mongolians compared to Tibetans and Han Chinese at comparable altitude. Whole-genome sequence from a DU Mongolian (Tianjiao1) shows that about 2% of the genomic variants, including more than 300 protein-coding changes, are specific to this individual. Our analyses of DU Mongolians and the first Mongolian genome provide valuable insight into genetic adaptation to extreme environments. PMID:23874230

  8. Using Whole-Genome Sequence Data to Predict Quantitative Trait Phenotypes in Drosophila melanogaster

    PubMed Central

    Ober, Ulrike; Ayroles, Julien F.; Stone, Eric A.; Richards, Stephen; Zhu, Dianhui; Gibbs, Richard A.; Stricker, Christian; Gianola, Daniel; Schlather, Martin; Mackay, Trudy F. C.; Simianer, Henner

    2012-01-01

    Predicting organismal phenotypes from genotype data is important for plant and animal breeding, medicine, and evolutionary biology. Genomic-based phenotype prediction has been applied for single-nucleotide polymorphism (SNP) genotyping platforms, but not using complete genome sequences. Here, we report genomic prediction for starvation stress resistance and startle response in Drosophila melanogaster, using ?2.5 million SNPs determined by sequencing the Drosophila Genetic Reference Panel population of inbred lines. We constructed a genomic relationship matrix from the SNP data and used it in a genomic best linear unbiased prediction (GBLUP) model. We assessed predictive ability as the correlation between predicted genetic values and observed phenotypes by cross-validation, and found a predictive ability of 0.239±0.008 (0.230±0.012) for starvation resistance (startle response). The predictive ability of BayesB, a Bayesian method with internal SNP selection, was not greater than GBLUP. Selection of the 5% SNPs with either the highest absolute effect or variance explained did not improve predictive ability. Predictive ability decreased only when fewer than 150,000 SNPs were used to construct the genomic relationship matrix. We hypothesize that predictive power in this population stems from the SNP–based modeling of the subtle relationship structure caused by long-range linkage disequilibrium and not from population structure or SNPs in linkage disequilibrium with causal variants. We discuss the implications of these results for genomic prediction in other organisms. PMID:22570636

  9. Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes.

    PubMed

    Deutsch, Samuel; Lyle, Robert; Dermitzakis, Emmanouil T; Attar, Homa; Subrahmanyan, Lakshman; Gehrig, Corinne; Parand, Leila; Gagnebin, Maryline; Rougemont, Jacques; Jongeneel, C Victor; Antonarakis, Stylianos E

    2005-12-01

    Inter-individual differences in gene expression are likely to account for an important fraction of phenotypic differences, including susceptibility to common disorders. Recent studies have shown extensive variation in gene expression levels in humans and other organisms, and that a fraction of this variation is under genetic control. We investigated the patterns of gene expression variation in a 25 Mb region of human chromosome 21, which has been associated with many Down syndrome (DS) phenotypes. Taqman real-time PCR was used to measure expression variation of 41 genes in lymphoblastoid cells of 40 unrelated individuals. For 25 genes found to be differentially expressed, additional analysis was performed in 10 CEPH families to determine heritabilities and map loci harboring regulatory variation. Seventy-six percent of the differentially expressed genes had significant heritabilities, and genomewide linkage analysis led to the identification of significant eQTLs for nine genes. Most eQTLs were in trans, with the best result (P=7.46 x 10(-8)) obtained for TMEM1 on chromosome 12q24.33. A cis-eQTL identified for CCT8 was validated by performing an association study in 60 individuals from the HapMap project. SNP rs965951 located within CCT8 was found to be significantly associated with its expression levels (P=2.5 x 10(-5)) confirming cis-regulatory variation. The results of our study provide a representative view of expression variation of chromosome 21 genes, identify loci involved in their regulation and suggest that genes, for which expression differences are significantly larger than 1.5-fold in control samples, are unlikely to be involved in DS-phenotypes present in all affected individuals. PMID:16251198

  10. Speciation, Phenotypic Variation and Plasticity: What Can Endocrine Disruptors Tell Us?

    PubMed Central

    Ayala-García, Braulio; López-Santibáñez Guevara, Marta; Marcos-Camacho, Lluvia I.; Fuentes-Farías, Alma L.; Meléndez-Herrera, Esperanza; Gutiérrez-Ospina, Gabriel

    2013-01-01

    Phenotype variability, phenotypic plasticity, and the inheritance of phenotypic traits constitute the fundamental ground of processes such as individuation, individual and species adaptation and ultimately speciation. Even though traditional evolutionary thinking relies on genetic mutations as the main source of intra- and interspecies phenotypic variability, recent studies suggest that the epigenetic modulation of gene transcription and translation, epigenetic memory, and epigenetic inheritance are by far the most frequent reliable sources of transgenerational variability among viable individuals within and across organismal species. Therefore, individuation and speciation should be considered as nonmutational epigenetic phenomena. PMID:23762055

  11. Phenotypic Variation Is Almost Entirely Independent of the Host-Pathogen Relationship in Clinical Isolates of S. aureus

    PubMed Central

    Land, Adrian D.; Hogan, Patrick; Fritz, Stephanie; Levin, Petra Anne

    2015-01-01

    Background A key feature of Staphylococcus aureus biology is its ability to switch from an apparently benign colonizer of ~30% of the population to a cutaneous pathogen, to a deadly invasive pathogen. Little is known about the mechanisms driving this transition or the propensity of different S. aureus strains to engender different types of host-pathogen interactions. At the same time, significant weight has been given to the role of specific in vitro phenotypes in S. aureus virulence. Biofilm formation, hemolysis and pigment formation have all been associated with virulence in mice. Design To determine if there is a correlation between in vitro phenotype and the three types of host-pathogen relationships commonly exhibited by S. aureus in the context of its natural human host, we assayed 300 clinical isolates for phenotypes implicated in virulence including hemolysis, sensitivity to autolysis, and biofilm formation. For comparative purposes, we also assayed phenotype in 9 domesticated S. aureus strains routinely used for analysis of virulence determinants in laboratory settings. Results Strikingly, the clinical strains exhibited significant phenotypic uniformity in each of the assays evaluated in this study. One exception was a small, but significant, correlation between an increased propensity for biofilm formation and isolation from skin and soft tissue infections (SSTIs). In contrast, we observed a high degree of phenotypic variation between common laboratory strains that exhibit virulence in mouse models. These data suggest the existence of significant evolutionary pressure on the S. aureus genome and highlight a role for host factors as a strong determinant of the host-pathogen relationship. In addition, the high degree of variation between laboratory strains emphasizes the need for caution when applying data obtained in one lab strain to the analysis of another. PMID:26098551

  12. Fad7 gene identification and fatty acids phenotypic variation in an olive collection by EcoTILLING and sequencing approaches.

    PubMed

    Sabetta, Wilma; Blanco, Antonio; Zelasco, Samanta; Lombardo, Luca; Perri, Enzo; Mangini, Giacomo; Montemurro, Cinzia

    2013-08-01

    The ?-3 fatty acid desaturases (FADs) are enzymes responsible for catalyzing the conversion of linoleic acid to ?-linolenic acid localized in the plastid or in the endoplasmic reticulum. In this research we report the genotypic and phenotypic variation of Italian Olea europaea L. germoplasm for the fatty acid composition. The phenotypic oil characterization was followed by the molecular analysis of the plastidial-type ?-3 FAD gene (fad7) (EC 1.14.19), whose full-length sequence has been here identified in cultivar Leccino. The gene consisted of 2635 bp with 8 exons and 5'- and 3'-UTRs of 336 and 282 bp respectively, and showed a high level of heterozygousity (1/110 bp). The natural allelic variation was investigated both by a LiCOR EcoTILLING assay and the PCR product direct sequencing. Only three haplotypes were identified among the 96 analysed cultivars, highlighting the strong degree of conservation of this gene. PMID:23685785

  13. Expression of sexual ornaments in a polymorphic species: phenotypic variation in response to environmental risk.

    PubMed

    Winandy, L; Denoël, M

    2015-05-01

    Secondary sexual traits may evolve under the antagonistic context of sexual and natural selection. In some polymorphic species, these traits are only expressed during the breeding period and are differently expressed in alternative phenotypes. However, it is unknown whether such phenotypes exhibit phenotypic plasticity of seasonal ornamentations in response to environmental pressures such as in the presence of fish (predation risk). This is an important question to understand the evolution of polyphenisms. We used facultative paedomorphosis in newts as a model system because it involves the coexistence of paedomorphs that retain gills in the adult stage with metamorphs that have undergone metamorphosis, but also because newts exhibit seasonal sexual traits. Our aim was therefore to determine the influence of fish on the development of seasonal ornamentation in the two phenotypes of the palmate newt (Lissotriton helveticus). During the entire newt breeding period, we assessed the importance of phenotype and fish presence with an information-theoretic approach. Our results showed that paedomorphs presented much less developed ornamentation than metamorphs and those ornamentations varied over time. Fish inhibited the development of sexual traits but differently between phenotypes: in contrast to metamorphs, paedomorphs lack the phenotypic plasticity of sexual traits to environmental risk. This study points out that internal and external parameters act in complex ways in the expression of seasonal sexual ornamentations and that similar environmental pressure can induce a contrasted evolution in alternative phenotypes. PMID:25847588

  14. Predator-Induced Phenotypic Plasticity in Larval Newts: Trade-Offs, Selection, and Variation in Nature

    Microsoft Academic Search

    Josh Van Buskirk; Benedikt R. Schmidt

    2000-01-01

    Phenotypic plasticity has important ecological consequences because the strengths of species interactions can change with the behavior and morphology of interacting individuals. Evolutionary studies of plasticity can predict conditions under which shifts in phenotypes will occur and, therefore, may modify species interactions. We studied evo- lutionary mechanisms maintaining an induced response to predators in Triturus newt larvae, which are among

  15. Variation in Phenotype, Parasite Load and Male Competitive Ability across a Cryptic Hybrid Zone

    PubMed Central

    Stuart-Fox, Devi; Godinho, Raquel; Goüy de Bellocq, Joëlle; Irwin, Nancy R.; Brito, José Carlos; Moussalli, Adnan; Široký, Pavel; Hugall, Andrew F.; Baird, Stuart J. E.

    2009-01-01

    Background Molecular genetic studies are revealing an increasing number of cryptic lineages or species, which are highly genetically divergent but apparently cannot be distinguished morphologically. This observation gives rise to three important questions: 1) have these cryptic lineages diverged in phenotypic traits that may not be obvious to humans; 2) when cryptic lineages come into secondary contact, what are the evolutionary consequences: stable co-existence, replacement, admixture or differentiation and 3) what processes influence the evolutionary dynamics of these secondary contact zones? Methodology/Principal Findings To address these questions, we first tested whether males of the Iberian lizard Lacerta schreiberi from two highly genetically divergent, yet morphologically cryptic lineages on either side of an east-west secondary contact could be differentiated based on detailed analysis of morphology, coloration and parasite load. Next, we tested whether these differences could be driven by pre-copulatory intra-sexual selection (male-male competition). Compared to eastern males, western males had fewer parasites, were in better body condition and were more intensely coloured. Although subtle environmental variation across the hybrid zone could explain the differences in parasite load and body condition, these were uncorrelated with colour expression, suggesting that the differences in coloration reflect heritable divergence. The lineages did not differ in their aggressive behaviour or competitive ability. However, body size, which predicted male aggressiveness, was positively correlated with the colour traits that differed between genetic backgrounds. Conclusions/Significance Our study confirms that these cryptic lineages differ in several aspects that are likely to influence fitness. Although there were no clear differences in male competitive ability, our results suggest a potential indirect role for intra-sexual selection. Specifically, if lizards use the colour traits that differ between genetic backgrounds to assess the size of potential rivals or mates, the resulting fitness differential favouring western males could result in net male-mediated gene flow from west to east across the current hybrid zone. PMID:19479073

  16. Missense variants in CFTR nucleotide-binding domains predict quantitative phenotypes associated with cystic fibrosis disease severity.

    PubMed

    Masica, David L; Sosnay, Patrick R; Raraigh, Karen S; Cutting, Garry R; Karchin, Rachel

    2015-04-01

    Predicting the impact of genetic variation on human health remains an important and difficult challenge. Often, algorithmic classifiers are tasked with predicting binary traits (e.g. positive or negative for a disease) from missense variation. Though useful, this arrangement is limiting and contrived, because human diseases often comprise a spectrum of severities, rather than a discrete partitioning of patient populations. Furthermore, labeling variants as causal or benign can be error prone, which is problematic for training supervised learning algorithms (the so-called garbage in, garbage out phenomenon). We explore the potential value of training classifiers using continuous-valued quantitative measurements, rather than binary traits. Using 20 variants from cystic fibrosis transmembrane conductance regulator (CFTR) nucleotide-binding domains and six quantitative measures of cystic fibrosis (CF) severity, we trained classifiers to predict CF severity from CFTR variants. Employing cross validation, classifier prediction and measured clinical/functional values were significantly correlated for four of six quantitative traits (correlation P-values from 1.35 × 10(-4) to 4.15 × 10(-3)). Classifiers were also able to stratify variants by three clinically relevant risk categories with 85-100% accuracy, depending on which of the six quantitative traits was used for training. Finally, we characterized 11 additional CFTR variants using clinical sweat chloride testing, two functional assays, or all three diagnostics, and validated our classifier using blind prediction. Predictions were within the measured sweat chloride range for seven of eight variants, and captured the differential impact of specific variants on the two functional assays. This work demonstrates a promising and novel framework for assessing the impact of genetic variation. PMID:25489051

  17. Identification of genes related to the phenotypic variations of a synthesized Paulownia (Paulownia tomentosa×Paulownia fortunei) autotetraploid.

    PubMed

    Li, Yongsheng; Fan, Guoqiang; Dong, Yanpeng; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Xu, Enkai; Niu, Suyan

    2014-12-15

    Paulownia is a fast-growing deciduous tree native to China. It has great economic importance for the pulp and paper industries, as well as ecological prominence in forest ecosystems. Paulownia is of much interest to plant breeder keen to explore new plant varieties by selecting on the basis of phenotype. A newly synthesized autotetraploid Paulownia exhibited advanced characteristics, such as greater yield, and higher resistance than the diploid tree. However, tissue-specific transcriptome and genomic data in public databases are not sufficient to understand the molecular mechanisms associated with genome duplication. To evaluate the effects of genome duplication on the phenotypic variations in Paulownia tomentosa×Paulownia fortunei, the transcriptomes of the autotetraploid and diploid Paulownia were compared. Using Illumina sequencing technology, a total of 82,934 All-unigenes with a mean length of 1109 bp were assembled. The data revealed numerous differences in gene expression between the two transcriptomes, including 718 up-regulated and 667 down-regulated differentially expressed genes between the two Paulownia trees. An analysis of the pathway and gene annotations revealed that genes involved in nucleotide sugar metabolism in plant cell walls were down-regulated, and genes involved in the light signal pathway and the biosynthesis of structural polymers were up-regulated in autotetraploid Paulownia. The differentially expressed genes may contribute to the observed phenotypic variations between diploid and autotetraploid Paulownia. These results provide a significant resource for understanding the variations in Paulownia polyploidization and will benefit future breeding work. PMID:25300252

  18. A Thirty-Year Study of Phenotypic and Genetic Variation of Blue Tits in Mediterranean Habitat Mosaics

    NSDL National Science Digital Library

    JACQUES BLONDEL, DONALD W. THOMAS, ANNE CHARMANTIER, PHILIPPE PERRET, PATRICE BOURGAULT, and MARCEL M. LAMBRECHTS (; )

    2006-08-01

    This peer reviewed article from BioScience investigate phenotypic variation in blue tits. In recent years, the study of phenotypic and genetic variation has been enhanced by combining genetic, physiological, demographic, and behavioral components of life histories. Using these new approaches, we address the problem of adaptation to environmental heterogeneity by examining in detail the variation of several fitness-related traits in a small passerine bird, the blue tit, which has been extensively studied in habitat mosaics of the Mediterranean region. The response of blue tits to spatial habitat heterogeneity depends on their range of dispersal relative to the size of habitat patches. Dispersal over short distances leads to local specialization, whereas dispersal over long distances leads to phenotypic plasticity. Gene flow between habitats of different quality may produce local maladaptation and a source-sink population structure. However, when habitat-specific divergent selection regimes are strong enough to oppose the effects of gene flow, local adaptation may arise on a scale that is much smaller than the scale of dispersal.

  19. Temporal variation in phenotypic gender and expected functional gender within and among individuals in an annual plant

    PubMed Central

    Austen, Emily J.; Weis, Arthur E.

    2014-01-01

    Background and Aims Adaptive explanations for variation in sex allocation centre on variation in resource status and variation in the mating environment. The latter can occur when dichogamy causes siring opportunity to vary across the flowering season. In this study, it is hypothesized that the widespread tendency towards declining fruit-set from first to last flowers on plants can similarly lead to a varying mating environment by causing a temporal shift in the quality (not quantity) of siring opportunities. Methods A numerical model was developed to examine the effects of declining fruit-set on the expected male versus female reproductive success (functional gender) of first and last flowers on plants, and of early- and late-flowering plants. Within- and among-plant temporal variation in pollen production, ovule production and fruit-set in 70 Brassica rapa plants was then characterized to determine if trends in male and female investment mirror expected trends in functional gender. Key Results Under a wide range of model conditions, functional femaleness decreased sharply in the last flowers on plants, and increased from early- to late-flowering plants in the population. In B. rapa, pollen production decreased more rapidly than ovule production from first to last flowers, leading to a within-plant increase in phenotypic femaleness. Among plants, ovule production decreased from early- to late-flowering plants, causing a temporal decrease in phenotypic femaleness. Conclusions The numerical model confirmed that declining fruit-set can drive temporal variation in functional gender, especially among plants. The discrepancy between observed trends in phenotypic gender in B. rapa and expected functional gender predicted by the numerical model does not rule out the possibility that male reproductive success decreases with later flowering onset. If so, plants may experience selection for early flowering through male fitness. PMID:24854170

  20. Genetic variation in mountain hemlock ( Tsuga mertensiana Bong.): quantitative and adaptive attributes

    Microsoft Academic Search

    Andy Benowicz; Yousry A. El-Kassaby

    1999-01-01

    Patterns of genetic variation for adaptive and quantitative attributes in mountain hemlock (Tsuga mertensiana (Bong.)) seedlings from British Columbia were examined at the population (provenance) and family levels. The population and family levels were represented by 12 provenances and 10 families from a single location, respectively. The adaptive attributes were related to gas exchange (net photosynthesis, transpiration rate, intercellular-to-ambient CO2

  1. THE EFFECT OF AN EXPERIMENTAL BOTTLENECK UPON QUANTITATIVE GENETIC VARIATION IN THE HOUSEFLY

    Microsoft Academic Search

    EDWIN H. BRYANT; LISA M. COMBS

    Effects of a population bottleneck (founder-flush cycle) upon quantitative ge- netic variation of morphometric traits were examined in replicated experimental lines of the housefly founded with one, four or 16 pairs of flies. Heritability and additive genetic variances for eight morphometric traits generally increased as a result of the bottleneck, but the pattern of increase among bottleneck sizes differed among

  2. Quantitative delineation of karyotype variation in Papaver as a measure of phylogenetic differentiation and origin

    Microsoft Academic Search

    U. C. Lavania; Sangeeta Srivastava

    Karyomorphology of 30 species of Papaver L. (Papaveraceae) and in situ localization of rDNA sites on chromosomes of P. somniferum was used to establish phylogenetic affinities, ancestry and chro- mosomal variation during speciation. A simple biometrical parameter, the 'Dispersion Index', was employed to facilitate quantitative evolutionary gradation between the closely related karyotypes that fall under the same class of karyotypic

  3. Quantitative variation in cystic fibrosis-associated proteins in cystic fibrosis patients, carriers, and controls

    Microsoft Academic Search

    A. Jamieson; Elizabeth Mackinlay; D. A. Aitken; A. Cooke; M. A. Ferguson-Smith

    1985-01-01

    Serum samples from patients with cystic fibrosis (CF), obligate heterozygotes, and normal controls have been examined by isoelectric focusing (IEF). Our results suggest that cystic fibrosis protein (CFP) is a normal serum protein exhibiting quantitative variation primarily dependent on possession of the CF allele. It is concluded that detection of CFP by IEF is an inappropriate screening test for the

  4. Geographic distribution of variation in quantitative traits in a world lentil collection

    Microsoft Academic Search

    W. Erskine; Y. Adham; L. Holly

    1989-01-01

    In a world lentil collection the distribution of variation amongst accessions from 13 major lentil-producing countries was examined on the basis of nine quantitative morphological characters by discriminant analysis and canonical analysis. Stepwise discriminant analysis revealed major differences between accessions from different countries. Three major regional groups were apparent: 1) a levantine group (Egypt, Jordan, Lebanon and Syria, 2) a

  5. Maintenance of phenotypic variation: repeatability, heritability and size-dependent processes in a wild brook trout population

    PubMed Central

    Letcher, Benjamin H; Coombs, Jason A; Nislow, Keith H

    2011-01-01

    Phenotypic variation in body size can result from within-cohort variation in birth dates, among-individual growth variation and size-selective processes. We explore the relative effects of these processes on the maintenance of wide observed body size variation in stream-dwelling brook trout (Salvelinus fontinalis). Based on the analyses of multiple recaptures of individual fish, it appears that size distributions are largely determined by the maintenance of early size variation. We found no evidence for size-dependent compensatory growth (which would reduce size variation) and found no indication that size-dependent survival substantially influenced body size distributions. Depensatory growth (faster growth by larger individuals) reinforced early size variation, but was relatively strong only during the first sampling interval (age-0, fall). Maternal decisions on the timing and location of spawning could have a major influence on early, and as our results suggest, later (>age-0) size distributions. If this is the case, our estimates of heritability of body size (body length = 0.25) will be dominated by processes that generate and maintain early size differences. As a result, evolutionary responses to environmental change that are mediated by body size may be largely expressed via changes in the timing and location of reproduction. PMID:25568008

  6. Maintenance of phenotypic variation: Repeatability, heritability and size-dependent processes in a wild brook trout population

    USGS Publications Warehouse

    Letcher, B.H.; Coombs, J.A.; Nislow, K.H.

    2011-01-01

    Phenotypic variation in body size can result from within-cohort variation in birth dates, among-individual growth variation and size-selective processes. We explore the relative effects of these processes on the maintenance of wide observed body size variation in stream-dwelling brook trout (Salvelinus fontinalis). Based on the analyses of multiple recaptures of individual fish, it appears that size distributions are largely determined by the maintenance of early size variation. We found no evidence for size-dependent compensatory growth (which would reduce size variation) and found no indication that size-dependent survival substantially influenced body size distributions. Depensatory growth (faster growth by larger individuals) reinforced early size variation, but was relatively strong only during the first sampling interval (age-0, fall). Maternal decisions on the timing and location of spawning could have a major influence on early, and as our results suggest, later (>age-0) size distributions. If this is the case, our estimates of heritability of body size (body length=0.25) will be dominated by processes that generate and maintain early size differences. As a result, evolutionary responses to environmental change that are mediated by body size may be largely expressed via changes in the timing and location of reproduction. Published 2011. This article is a US Government work and is in the public domain in the USA.

  7. Hsp90 and the quantitative variation of wing shape in Drosophila melanogaster.

    PubMed

    Debat, Vincent; Milton, Claire C; Rutherford, Suzannah; Klingenberg, Christian Peter; Hoffmann, Ary A

    2006-12-01

    The molecular chaperone protein Hsp90 has been widely discussed as a candidate gene for developmental buffering. We used the methods of geometric morphometrics to analyze its effects on the variation among individuals and fluctuating asymmetry of wing shape in Drosophila melanogaster. Three different experimental approaches were used to reduce Hsp90 activity. In the first experiment, developing larvae were reared in food containing a specific inhibitor of Hsp90, geldanamycin, but neither individual variation nor fluctuating asymmetry was altered. Two further experiments generated lines of genetically identical flies carrying mutations of Hsp83, the gene encoding the Hsp90 protein, in heterozygous condition in nine different genetic backgrounds. The first of these, introducing entire chromosomes carrying either of two Hsp83 mutations, did not increase shape variation or asymmetry over a wild-type control in any of the nine genetic backgrounds. In contrast, the third experiment, in which one of these Hsp83 alleles was introgressed into the wild-type background that served as the control, induced an increase in both individual variation and fluctuating asymmetry within each of the nine genetic backgrounds. No effect of Hsp90 on the difference among lines was detected, pro,iding no evidence for cryptic genetic variation of wing shape. Overall, these results suggest that Hsp90 contributes to, but is not controlling, the buffering of phenotypic variation in wing shape. PMID:17263114

  8. Phenotyping of tianma-stimulated differentiated rat neuronal b104 cells by quantitative proteomics.

    PubMed

    Sundaramurthi, Husvinee; Manavalan, Arulmani; Ramachandran, Umamaheswari; Hu, Jiang-Miao; Sze, Siu Kwan; Heese, Klaus

    2012-01-01

    Gastrodia elata blume (tianma) is a traditional Chinese herb often used in the treatment of convulsions, headaches, and hypertension. Although interest in neuronal-related actions of tianma is increasing, minimal studies have been conducted to determine its specific effects on neuronal cells. This study was designed to examine the effects of tianma on the metabolism in differentiated neuroblastoma cells using the isobaric tag for relative and absolute quantitation (iTRAQ) technology. Stimulation of these cells with tianma caused changes in the expression of 38 proteins that were subsequently classified according to their physiological functions and association with neurodegenerative diseases. We identified six proteins with altered functional activities in neurodegenerative disease states that were modulated by tianma: triosephosphate isomerase (Tpi1), peptidyl-prolyl cis-trans isomerase A (Ppia), neural cell adhesion molecule 1 (Ncam1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (Uchl1), septin-2 (Sept2) and heat shock protein 90 (Hsp90aa1). We postulate that tianma mediates its neuroprotective effects via upregulation of Ncam1, Hsp90aa1, Tpi1 and Ppia while downregulating Sept2 and Uchl1. These changes in protein expression aid in the restoration of the intracellular environment to a metabolically balanced state, promoting cell survival. Based on these observed data, we conclude that tianma has therapeutic potential, especially for neurodegenerative diseases. PMID:22094351

  9. Transcriptional Analysis of a Photorhabdus sp. Variant Reveals Transcriptional Control of Phenotypic Variation and Multifactorial Pathogenicity in Insects?

    PubMed Central

    Lanois, A.; Pages, S.; Bourot, S.; Canoy, A.-S.; Givaudan, A.; Gaudriault, S.

    2011-01-01

    Photorhabdus luminescens lives in a mutualistic association with entomopathogenic nematodes and is pathogenic for insects. Variants of Photorhabdus frequently arise irreversibly and are studied because they have altered phenotypic traits that are potentially important for the host interaction. VAR* is a colonial and phenotypic variant displaying delayed pathogenicity when directly injected into the insect, Spodoptera littoralis. In this study, we evaluated the role of transcriptomic modulation in determining the phenotypic variation and delayed pathogenicity of VAR* with respect to the corresponding wild-type form, TT01?. A P. luminescens microarray identified 148 genes as differentially transcribed between VAR* and TT01?. The net regulator status of VAR* was found to be significantly modified. We also observed in VAR* a decrease in the transcription of genes supporting certain phenotypic traits, such as pigmentation, crystalline inclusion, antibiosis, and protease and lipase activities. Three genes encoding insecticidal toxins (pit and pirB) or putative insecticidal toxins (xnp2) were less transcribed in VAR* than in the TT01?. The overexpression of these genes was not sufficient to restore the virulence of VAR* to the levels of ??01?, which suggests that the lower virulence of VAR* does not result from impaired toxemia in insects. Three loci involved in oxidative stress responses (sodA, katE, and the hca operon) were found to be downregulated in VAR*. This is consistent with the greater sensitivity of VAR* to H2O2 and may account for the impaired bacteremia in the hemolymph of S. littoralis larvae observed with VAR*. In conclusion, we demonstrate here that some phenotypic traits of VAR* are regulated transcriptionally and highlight the multifactorial nature of pathogenicity in insects. PMID:21131515

  10. Multi-character approach reveals a discordant pattern of phenotypic variation during ontogeny in Culex pipiens biotypes (Diptera: Culicidae).

    PubMed

    Krtini?, B; Ludoški, J; Milankov, V

    2015-02-01

    Culex (Culex) pipiens s.l. (Diptera: Culicidae) comprises two distinct biotypes, pipiens ('rural') and molestus ('urban'), both of which are thought to have differing capacities due to different host preferences. To better understand West Nile encephalitis epidemiology and improve risk assessment, local distinction between these forms is essential. This study assesses phenotypic variation at larval and adult stages of 'urban' and 'rural' biotypes of the species by complementary use of meristic, univariate and multivariate traits analyzed by traditional and geometric morphometrics. Third- and fourth-instar larvae from a broad area of the city of Novi Sad (Serbia) were collected and reared in the laboratory. After adult eclosion, the sex of each larva was recorded based on the sex of the corresponding adult. Examination of the association between variations of larval traits revealed contrasting variations regarding pecten spines vs. siphonal size and siphonal shape in the 'rural' biotype. Siphons of larvae collected in marshes and forest ecosystems outside urban areas were found to be the largest, but possessed the smallest number of pecten spines. In addition, statistically significant female-biased sexual dimorphism was observed in siphonal size, wing size and wing shape. Finally, we propose that an integrative approach is essential in delimitation of Cx. pipiens s.l. biotypes, since their differentiation was not possible based solely on larval and adult traits. Our findings shed light on the phenotypic plasticity important for population persistence in the changing environment of these medically important taxa. PMID:25424880

  11. Clonal expansion of the Pseudogymnoascus destructans genotype in North America is accompanied by significant variation in phenotypic expression.

    PubMed

    Khankhet, Jordan; Vanderwolf, Karen J; McAlpine, Donald F; McBurney, Scott; Overy, David P; Slavic, Durda; Xu, Jianping

    2014-01-01

    Pseudogymnoascus destructans is the causative agent of an emerging infectious disease that threatens populations of several North American bat species. The fungal disease was first observed in 2006 and has since caused the death of nearly six million bats. The disease, commonly known as white-nose syndrome, is characterized by a cutaneous infection with P. destructans causing erosions and ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on sequences from eight loci have found that isolates of P. destructans from bats in the US all belong to one multilocus genotype. Using the same multilocus sequence typing method, we found that isolates from eastern and central Canada also had the same genotype as those from the US, consistent with the clonal expansion of P. destructans into Canada. However, our PCR fingerprinting revealed that among the 112 North American isolates we analyzed, three, all from Canada, showed minor genetic variation. Furthermore, we found significant variations among isolates in mycelial growth rate; the production of mycelial exudates; and pigment production and diffusion into agar media. These phenotypic differences were influenced by culture medium and incubation temperature, indicating significant variation in environmental condition--dependent phenotypic expression among isolates of the clonal P. destructans genotype in North America. PMID:25122221

  12. A Genome-Wide Association Study of Schizophrenia Using Brain Activation as a Quantitative Phenotype

    PubMed Central

    Potkin, Steven G.; Turner, Jessica A.; Guffanti, Guia; Lakatos, Anita; Fallon, James H.; Nguyen, Dana D.; Mathalon, Daniel; Ford, Judith; Lauriello, John; Macciardi, Fabio

    2009-01-01

    Background: Genome-wide association studies (GWASs) are increasingly used to identify risk genes for complex illnesses including schizophrenia. These studies may require thousands of subjects to obtain sufficient power. We present an alternative strategy with increased statistical power over a case-control study that uses brain imaging as a quantitative trait (QT) in the context of a GWAS in schizophrenia. Methods: Sixty-four subjects with chronic schizophrenia and 74 matched controls were recruited from the Functional Biomedical Informatics Research Network (FBIRN) consortium. Subjects were genotyped using the Illumina HumanHap300 BeadArray and were scanned while performing a Sternberg Item Recognition Paradigm in which they learned and then recognized target sets of digits in an functional magnetic resonance imaging protocol. The QT was the mean blood oxygen level–dependent signal in the dorsolateral prefrontal cortex during the probe condition for a memory load of 3 items. Results: Three genes or chromosomal regions were identified by having 2 single-nucleotide polymorphisms (SNPs) each significant at P < 10?6 for the interaction between the imaging QT and the diagnosis (ROBO1-ROBO2, TNIK, and CTXN3-SLC12A2). Three other genes had a significant SNP at <10?6 (POU3F2, TRAF, and GPC1). Together, these 6 genes/regions identified pathways involved in neurodevelopment and response to stress. Conclusion: Combining imaging and genetic data from a GWAS identified genes related to forebrain development and stress response, already implicated in schizophrenic dysfunction, as affecting prefrontal efficiency. Although the identified genes require confirmation in an independent sample, our approach is a screening method over the whole genome to identify novel SNPs related to risk for schizophrenia. PMID:19023125

  13. Quantitative measurement of phase variation amplitude of ultrasonic diffraction grating based on diffraction spectral analysis

    SciTech Connect

    Pan, Meiyan, E-mail: yphantomohive@gmail.com; Zeng, Yingzhi; Huang, Zuohua, E-mail: zuohuah@163.com [Laboratory of Quantum Engineering and Quantum Materials, School of Physics and Telecommunication Engineering, South China Normal University, Guangzhou, Guangdong 510006 (China)

    2014-09-15

    A new method based on diffraction spectral analysis is proposed for the quantitative measurement of the phase variation amplitude of an ultrasonic diffraction grating. For a traveling wave, the phase variation amplitude of the grating depends on the intensity of the zeroth- and first-order diffraction waves. By contrast, for a standing wave, this amplitude depends on the intensity of the zeroth-, first-, and second-order diffraction waves. The proposed method is verified experimentally. The measured phase variation amplitude ranges from 0 to 2?, with a relative error of approximately 5%. A nearly linear relation exists between the phase variation amplitude and driving voltage. Our proposed method can also be applied to ordinary sinusoidal phase grating.

  14. Variation in Phenotype, Parasite Load and Male Competitive Ability across a Cryptic Hybrid Zone

    Microsoft Academic Search

    Devi Stuart-Fox; Raquel Godinho; Joëlle Goüy de Bellocq; Nancy R. Irwin; José Carlos Brito; Adnan Moussalli; Pavel Siroký; Andrew F. Hugall; Stuart J. E. Baird; Jon R. Bridle

    2009-01-01

    BackgroundMolecular genetic studies are revealing an increasing number of cryptic lineages or species, which are highly genetically divergent but apparently cannot be distinguished morphologically. This observation gives rise to three important questions: 1) have these cryptic lineages diverged in phenotypic traits that may not be obvious to humans; 2) when cryptic lineages come into secondary contact, what are the evolutionary

  15. Cyclomorphosis in Daphnia galeata mendotae : variation and stability in phenotypic cycles

    Microsoft Academic Search

    Mona A. Mort; J. W. Goethe-Universitdt

    1989-01-01

    Phenotypic change is studied in a cyclomorphicDaphnia galeata mendotae population known from previous studies to be clonally diverse. Morphological analyses revealed cyclical changes in both adult and juvenile helmet length and tailspine length which were: 1) strongly correlated with mean water temperature; and 2) repeated annually during the 3-year study period. Field populations exhibited high (5% to 30%) coefficients of

  16. Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

    Microsoft Academic Search

    Amaury Vaysse; Abhirami Ratnakumar; Thomas Derrien; Erik Axelsson; Gerli Rosengren Pielberg; Snaevar Sigurdsson; Tove Fall; Eija H. Seppälä; Mark S. T. Hansen; Cindy T. Lawley; Elinor K. Karlsson; Danika Bannasch; Carles Vilà; Hannes Lohi; Francis Galibert; Merete Fredholm; Jens Häggström; Åke Hedhammar; Catherine André; Kerstin Lindblad-Toh; Christophe Hitte; Matthew T. Webster; H. Fieten; P. A. J. Leegwater

    2011-01-01

    The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first

  17. The contributions of evolutionary divergence and phenotypic plasticity to geographic variation in the

    E-print Network

    Irschick, Duncan J.

    in the western fence lizard, Sceloporus occidentalis CHRISTINE R. BUCKLEY1 *, DUNCAN J. IRSCHICK2 and STEPHEN C ontogeny to shape organismal phenotypes. We incubated eggs of the western fence lizard, Sceloporus occidentalis, from four populations (representing two latitudes and altitudes) in either a warm or cool

  18. Environmental effects on molecular and phenotypic variation in populations of Eruca sativa across a steep climatic gradient

    PubMed Central

    Westberg, Erik; Ohali, Shachar; Shevelevich, Anatoly; Fine, Pinchas; Barazani, Oz

    2013-01-01

    Abstract In Israel Eruca sativa has a geographically narrow distribution across a steep climatic gradient that ranges from mesic Mediterranean to hot desert environments. These conditions offer an opportunity to study the influence of the environment on intraspecific genetic variation. For this, we combined an analysis of neutral genetic markers with a phenotypic evaluation in common-garden experiments, and environmental characterization of populations that included climatic and edaphic parameters, as well as geographic distribution. A Bayesian clustering of individuals from nine representative populations based on amplified fragment length polymorphism (AFLP) divided the populations into a southern and a northern geographic cluster, with one admixed population at the geographic border between them. Linear mixed models, with cluster added as a grouping factor, revealed no clear effects of environment or geography on genetic distances, but this may be due to a strong association of geography and environment with genetic clusters. However, environmental factors accounted for part of the phenotypic variation observed in the common-garden experiments. In addition, candidate loci for selection were identified by association with environmental parameters and by two outlier methods. One locus, identified by all three methods, also showed an association with trichome density and herbivore damage, in net-house and field experiments, respectively. Accordingly, we propose that because trichomes are directly linked to defense against both herbivores and excess radiation, they could potentially be related to adaptive variation in these populations. These results demonstrate the value of combining environmental and phenotypic data with a detailed genetic survey when studying adaptation in plant populations. This article describes the use of several types of data to estimate the influence of the environment on intraspecific genetic variation in populations originating from a steep climatic gradient. In addition to molecular marker data, we made use of phenotypic evaluation from common garden experiments, and a broad GIS based environmental data with edaphic information gathered in the field. This study, among others, lead to the identification of an outlier locus with an association to trichome formation and herbivore defense, and its ecological adaptive value is discussed. PMID:24567822

  19. Variation in human brains may facilitate evolutionary change toward a limited range of phenotypes

    PubMed Central

    Charvet, Christine J.; Darlington, Richard B.; Finlay, Barbara L.

    2013-01-01

    Individual variation is the foundation for evolutionary change, but little is known about the nature of normal variation between brains. Phylogenetic variation across mammalian brains is characterized by high inter-correlations in brain region volumes, distinct allometric scaling for each brain region and the relative independence in olfactory and limbic structures volumes from the rest of the brain. Previous work examining brain variation in individuals of some domesticated species showed that these three features of phylogenetic variation were mirrored in individual variation. We extend this analysis to the human brain and 10 of its subdivisions (e.g., isocortex, hippocampus) by using magnetic resonance imaging scans of 90 human brains ranging between 16 to 25 years of age. Human brain variation resembles both the individual variation seen in other species, and variation observed across mammalian species. That is, the relative differences in the slopes of each brain region compared to medulla size within humans and between mammals are concordant, and limbic structures scale with relative independence from other brain regions. This non-random pattern of variation suggests that developmental programs channel the variation available for selection. PMID:23363667

  20. Histological variations in juvenile polyp phenotype correlate with genetic defect underlying juvenile polyposis

    PubMed Central

    van Hattem, W. Arnout; Langeveld, Danielle; de Leng, Wendy W. J.; Morsink, Folkert H.; van Diest, Paul J.; Iacobuzio-Donahue, Christine A.; Giardiello, Francis M.; Offerhaus, G. Johan A.; Brosens, Lodewijk A. A.

    2011-01-01

    Background Juvenile polyps are distinct hamartomatous malformations of the gastrointestinal tract that may occur in the heritable juvenile polyposis syndrome (JPS) or sporadically. Histologically, juvenile polyps are characterised by a marked increase of the stromal cell compartment but, an epithelial phenotype has also been reported. JPS has an increased risk of colorectal cancer but sporadic juvenile polyps do not. In 50–60% of JPS patients a germline mutation of the TGF-?/BMP pathway genes SMAD4 or BMPR1A is found. This study compares the histological phenotype of juvenile polyps with a SMAD4 or BMPR1A germline mutation and sporadic juvenile polyps. Methods H&E slides of 65 JPS polyps and 25 sporadic juvenile polyps were reviewed for histological features and dysplasia. Systematic random crypt and stroma counts were obtained by count stereology and a crypt-stroma ratio was determined. All polyps were subsequently categorised as type A (crypt-stroma ratio <1.00) or type B (crypt-stroma ratio ?1.00), the latter referring to the epithelial phenotype. Cell cycle activity was assessed using immunohistochemistry of the proliferation marker Ki67, and mutation analysis was conducted for KRAS and APC to determine the involvement of the adenoma-carcinoma sequence. Results Juvenile polyps with a SMAD4 germline mutation were predominantly type B, whereas, type A was more common among juvenile polyps with a BMPR1A germline mutation, but this distinction could not be ascribed to differences in cell cycle activity. Dysplasia was equally common in JPS polyps with either a SMAD4 or BMPR1A germline mutation, where the involvement of the adenoma-carcinoma sequence does not seem to play a distinct role. Conclusion juvenile polyps in the setting of JPS exhibit distinct phenotypes correlating with the underlying genetic defect. PMID:21412070

  1. Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp. petraea

    Microsoft Academic Search

    Matthew P. Davey; F. Ian Woodward; W. Paul Quick

    2009-01-01

    Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations\\u000a growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local\\u000a abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold

  2. Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

    PubMed Central

    Acland, Gregory M.

    2014-01-01

    Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

  3. Extreme phenotypic variation in Cetraria aculeata (lichenized Ascomycota): adaptation or incidental modification?

    PubMed Central

    Pérez-Ortega, Sergio; Fernández-Mendoza, Fernando; Raggio, José; Vivas, Mercedes; Ascaso, Carmen; Sancho, Leopoldo G.; Printzen, Christian; de los Ríos, Asunción

    2012-01-01

    Background and Aims Phenotypic variability is a successful strategy in lichens for colonizing different habitats. Vagrancy has been reported as a specific adaptation for lichens living in steppe habitats around the world. Among the facultatively vagrant species, the cosmopolitan Cetraria aculeata apparently forms extremely modified vagrant thalli in steppe habitats of Central Spain. The aim of this study was to investigate whether these changes are phenotypic plasticity (a single genotype producing different phenotypes), by characterizing the anatomical and ultrastructural changes observed in vagrant morphs, and measuring differences in ecophysiological performance. Methods Specimens of vagrant and attached populations of C. aculeata were collected on the steppes of Central Spain. The fungal internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GPD) and the large sub-unit of the mitochondrial ribosomal DNA (mtLSUm), and the algal ITS and actin were studied within a population genetics framework. Semi-thin and ultrathin sections were analysed by means of optical, scanning electron and transmission electron microscopy. Gas exchange and chlorophyll fluorescence were used to compare the physiological performance of both morphs. Key Results and Conclusions Vagrant and attached morphs share multilocus haplotypes which may indicate that they belong to the same species in spite of their completely different anatomy. However, differentiation tests suggested that vagrant specimens do not represent a random sub-set of the surrounding population. The morphological differences were related to anatomical and ultrastructural differences. Large intercalary growth rates of thalli after the loss of the basal–apical thallus polarity may be the cause of the increased growth shown by vagrant specimens. The anatomical and morphological changes lead to greater duration of ecophysiological activity in vagrant specimens. Although the anatomical and physiological changes could be chance effects, the genetic differentiation between vagrant and attached sub-populations and the higher biomass of the former show fitness effects and adaptation to dry environmental conditions in steppe habitats. PMID:22451601

  4. SNP array mapping of 20p deletions: Genotypes, Phenotypes and Copy Number Variation

    PubMed Central

    Kamath, Binita M.; Thiel, Brian D.; Gai, Xiaowu; Conlin, Laura K.; Munoz, Pedro S.; Glessner, Joseph; Clark, Dinah; Warthen, Daniel M.; Shaikh, Tamim H.; Mihci, Ercan; Piccoli, David A.; Grant, Struan F.A.; Hakonarson, Hakon; Krantz, Ian D.; Spinner, Nancy B.

    2008-01-01

    The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients and 5 relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to 1) more accurately determine the deletion sizes, 2) identify and compare breakpoints, 3) establish genotype/phenotype correlations and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95kb to 14.62Mb, and all of the breakpoints were unique. Eleven patients had deletions between 95kb and 4Mb and these individuals had normal development, with no anomalies outside of those associated with Alagille syndrome. The proximal and distal boundaries of these eleven deletions constitute a 5.4MB region, and we propose that haploinsufficiency for only 1 of the 12 genes in this region causes phenotypic abnormalities. This defines the JAG1 associated critical region, in which deletions do not confer findings other than those associated with Alagille syndrome. The other 10 patients had deletions between 3.28Mb and 14.62Mb, which extended outside the critical region, and notably, all of these patients, had developmental delay. This group had other findings such as autism, scoliosis and bifid uvula. We identified 47 additional polymorphic genome-wide copy number variants (>20 SNPs), with 0–5 variants called per patient. Deletions of the short arm of chromosome 20 are associated with relatively mild and limited clinical anomalies. The use of SNP arrays provides accurate high-resolution definition of genomic abnormalities. PMID:19058200

  5. MitoLSDB: A Comprehensive Resource to Study Genotype to Phenotype Correlations in Human Mitochondrial DNA Variations

    PubMed Central

    K, Shamnamole; Jalali, Saakshi; Scaria, Vinod; Bhardwaj, Anshu

    2013-01-01

    Human mitochondrial DNA (mtDNA) encodes a set of 37 genes which are essential structural and functional components of the electron transport chain. Variations in these genes have been implicated in a broad spectrum of diseases and are extensively reported in literature and various databases. In this study, we describe MitoLSDB, an integrated platform to catalogue disease association studies on mtDNA (http://mitolsdb.igib.res.in). The main goal of MitoLSDB is to provide a central platform for direct submissions of novel variants that can be curated by the Mitochondrial Research Community. MitoLSDB provides access to standardized and annotated data from literature and databases encompassing information from 5231 individuals, 675 populations and 27 phenotypes. This platform is developed using the Leiden Open (source) Variation Database (LOVD) software. MitoLSDB houses information on all 37 genes in each population amounting to 132397 variants, 5147 unique variants. For each variant its genomic location as per the Revised Cambridge Reference Sequence, codon and amino acid change for variations in protein-coding regions, frequency, disease/phenotype, population, reference and remarks are also listed. MitoLSDB curators have also reported errors documented in literature which includes 94 phantom mutations, 10 NUMTs, six documentation errors and one artefactual recombination. MitoLSDB is the largest repository of mtDNA variants systematically standardized and presented using the LOVD platform. We believe that this is a good starting resource to curate mtDNA variants and will facilitate direct submissions enhancing data coverage, annotation in context of pathogenesis and quality control by ensuring non-redundancy in reporting novel disease associated variants. PMID:23585830

  6. Genetic variation in HIF signaling underlies quantitative variation in physiological and life-history traits within lowland butterfly populations.

    PubMed

    Marden, James H; Fescemyer, Howard W; Schilder, Rudolf J; Doerfler, William R; Vera, Juan C; Wheat, Christopher W

    2013-04-01

    Oxygen conductance to the tissues determines aerobic metabolic performance in most eukaryotes but has cost/benefit tradeoffs. Here we examine in lowland populations of a butterfly a genetic polymorphism affecting oxygen conductance via the hypoxia-inducible factor (HIF) pathway, which senses intracellular oxygen and controls the development of oxygen delivery networks. Genetically distinct clades of Glanville fritillary (Melitaea cinxia) across a continental scale maintain, at intermediate frequencies, alleles in a metabolic enzyme (succinate dehydrogenase, SDH) that regulates HIF-1?. One Sdhd allele was associated with reduced SDH activity rate, twofold greater cross-sectional area of tracheoles in flight muscle, and better flight performance. Butterflies with less tracheal development had greater post-flight hypoxia signaling, swollen & disrupted mitochondria, and accelerated aging of flight metabolic performance. Allelic associations with metabolic and aging phenotypes were replicated in samples from different clades. Experimentally elevated succinate in pupae increased the abundance of HIF-1? and expression of genes responsive to HIF activation, including tracheal morphogenesis genes. These results indicate that the hypoxia inducible pathway, even in lowland populations, can be an important axis for genetic variation underlying intraspecific differences in oxygen delivery, physiological performance, and life history. PMID:23550759

  7. Phenotype Variation in Human Immunodeficiency virus Type 1 Transmission and Disease Progression

    PubMed Central

    Cavarelli, Mariangela; Scarlatti, Gabriella

    2009-01-01

    Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed. PMID:19893208

  8. A Comparison of Isozyme and Quantitative Genetic Variation in Pinus contorta ssp. latifolia by FsT

    Microsoft Academic Search

    Rong-Cai Yang; Francis C. Yeh; Alvin D. Yanchukt

    We employed Fstatistics to analyze quantitative and isozyme variation among five populations of Pinus contorta ssp. latifolia, a wind-pollinated outcrossing conifer with wide and continuous distribution in west North America. Estimates of population differentiation (&) for six quantitative traits were compared with the overall estimate of the differentiation (fir) from 19 isozymes that tested neutral to examine whether similar evolutionary

  9. Genetic and Phenotypic Variation of FMDV During Serial Passages in a Natural Host

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-Mouth Disease Virus (FMDV) exhibits high mutation rates during replication that have been suggested to be of adaptive value. However, even though genetic variation in RNA viruses has been extensively examined during virus replication in a wide variety of in vitro cell cultures, very little ...

  10. Contribution of allelic variations in transporters to the phenotype of drug response

    Microsoft Academic Search

    Julia Kirchheiner; Dirk Gründemann; Edgar Schömig

    2006-01-01

    Pharmacogenomics seeks to explain the variability in drug response. Neurotransmitter transporters from the SLCA6 family are direct or indirect targets for psychotropic drugs, and their genetic variations may directly influence response to antidepressant or antipsychotic drugs. Furthermore, drug transporters located in natural barriers, such as the blood brain barrier, may influence response to psychoactive substrates.In the 5?-upstream regulatory region of

  11. Coat Color Variation in Rock Pocket Mice (Chaetodipus intermedius): From Genotype to Phenotype

    E-print Network

    Hoekstra, Hopi E.

    crinitus), the deer mouse (Peromyscus maniculatus), the oldfield mouse (Peromyscus polionotus), Botta and between species. Examples of intraspecific color variation in rodents include the canyon mouse (Peromyscus (Sumner, 1921; Dice and Blossom, 1937), studies in Peromyscus have clearly demonstrated that owls

  12. DNA variation in the phenotypically-diverse brown alga Saccharina japonica

    PubMed Central

    2012-01-01

    Background Saccharina japonica (Areschoug) Lane, Mayes, Druehl et Saunders is an economically important and highly morphologically variable brown alga inhabiting the northwest Pacific marine waters. On the basis of nuclear (ITS), plastid (rbcLS) and mitochondrial (COI) DNA sequence data, we have analyzed the genetic composition of typical Saccharina japonica (TYP) and its two common morphological varieties, known as the “longipes” (LON) and “shallow-water” (SHA) forms seeking to clarify their taxonomical status and to evaluate the possibility of cryptic species within S. japonica. Results The data show that the TYP and LON forms are very similar genetically in spite of drastic differences in morphology, life history traits, and ecological preferences. Both, however, are genetically quite different from the SHA form. The two Saccharina lineages are distinguished by 109 fixed single nucleotide differences as well as by seven fixed length polymorphisms (based on a 4,286?bp concatenated dataset that includes three gene regions). The GenBank database reveals a close affinity of the TYP and LON forms to S. japonica and the SHA form to S. cichorioides. The three gene markers used in the present work have different sensitivity for the algal species identification. COI gene was the most discriminant gene marker. However, we have detected instances of interspecific COI recombination reflecting putative historical hybridization events between distantly related algal lineages. The recombinant sequences show highly contrasted level of divergence in the 5’- and 3’- regions of the gene, leading to significantly different tree topologies depending on the gene segment (5’- or 3’-) used for tree reconstruction. Consequently, the 5’-COI “barcoding” region (~ 650?bp) can be misleading for identification purposes, at least in the case of algal species that might have experienced historical hybridization events. Conclusion Taking into account the potential roles of phenotypic plasticity in evolution, we conclude that the TYP and LON forms represent examples of algae phenotypic diversification that enables successful adaptation to contrasting shallow- and deep-water marine environments, while the SHA form is very similar to S. cichorioides and should be considered a different species. Practical applications for algal management and conservation are briefly considered. PMID:22784095

  13. Phenotypic and genotypic background underlying variations in fatty acid composition and sensory parameters in European bovine breeds

    PubMed Central

    2014-01-01

    Background Consuming moderate amounts of lean red meat as part of a balanced diet valuably contributes to intakes of essential nutrients. In this study, we merged phenotypic and genotypic information to characterize the variation in lipid profile and sensory parameters and to represent the diversity among 15 cattle populations. Correlations between fat content, organoleptic characteristics and lipid profiles were also investigated. Methods A sample of 436 largely unrelated purebred bulls belonging to 15 breeds and reared under comparable management conditions was analyzed. Phenotypic data -including fatness score, fat percentage, individual fatty acids (FA) profiles and sensory panel tests- and genotypic information from 11 polymorphisms was used. Results The correlation coefficients between muscle total lipid measurements and absolute vs. relative amounts of polyunsaturated FA (PUFA) were in opposite directions. Increasing carcass fat leads to an increasing amount of FAs in triglycerides, but at the same time the relative amount of PUFAs is decreasing, which is in concordance with the negative correlation obtained here between the percentage of PUFA and fat measurements, as well as the weaker correlation between total phospholipids and total lipid muscle content compared with neutral lipids. Concerning organoleptic characteristics, a negative correlation between flavour scores and the percentage of total PUFA, particularly to n-6 fraction, was found. The correlation between juiciness and texture is higher than with flavour scores. The distribution of SNPs plotted by principal components analysis (PCA) mainly reflects their known trait associations, although influenced by their specific breed allele frequencies. Conclusions The results presented here help to understand the phenotypic and genotypic background underlying variations in FA composition and sensory parameters between breeds. The wide range of traits and breeds studied, along with the genotypic information on polymorphisms previously associated with different lipid traits, provide a broad characterization of beef meat, which allows giving a better response to the variety of consumers’ preferences. Also, the development and implementation of low-density SNP panels with predictive value for economically important traits, such as those summarized here, may be used to improve production efficiency and meat quality in the beef industry. PMID:24735897

  14. LIFE-HISTORY VARIATION IN THE SAGEBRUSH LIZARD: PHENOTYPIC PLASTICITY OR LOCAL ADAPTATION?

    Microsoft Academic Search

    Michael W. Sears

    2003-01-01

    We performed a laboratory common-environment study to determine the genetic and environmental sources of variation in growth rates of the sagebrush lizard (Sceloporus graciosus). Hatchling lizards were reared from gravid females collected from three study populations along an elevational gradient in southern Utah, USA. Hatchlings were fed ad libidum and were maintained on a 14:10 light:dark cycle, with temperatures at

  15. Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

    PubMed Central

    2014-01-01

    Background Etiology of complex disorders, such as cataract and neurodegenerative diseases including age-related macular degeneration (AMD), remains poorly understood due to the paucity of animal models, fully replicating the human disease. Previously, two quantitative trait loci (QTLs) associated with early cataract, AMD-like retinopathy, and some behavioral aberrations in senescence-accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and WAG rats. To confirm the findings, we generated interval-specific congenic strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome 1 in the WAG strain. Both congenic strains displayed early cataract and retinopathy but differed clinically from OXYS rats. Here we applied a high-throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the candidate genes and functional pathways that may be responsible for these differences and can contribute to the development of the senescence-accelerated phenotype of OXYS rats. Results First, the size and map position of QTL-derived congenic segments were determined by comparative analysis of coding single-nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and congenic retinal RNAs after sequencing. The transferred locus was not what we expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed. Coherent sets of differentially expressed genes were identified when we compared RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats. The genes most different in the average expression level between the congenic strains included those generally associated with the Wnt, integrin, and TGF-? signaling pathways, widely involved in neurodegenerative processes. Several candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs, Car9 and Fn1) were found to be either polymorphic in the congenic loci or differentially expressed between the strains. These genes may contribute to the development of cataract and retinopathy. Conclusions This study is the first RNA-Seq analysis of the rat retinal transcriptome generated with 40 mln sequencing read depth. The integration of QTL and transcriptomic analyses in our study forms the basis of future research into the relationship between the candidate genes within the congenic regions and specific changes in the retinal transcriptome as possible causal mechanisms that underlie age-associated disorders. PMID:25563673

  16. Phenotypic and genotypic variation in Giardia lamblia isolates during chronic infection.

    PubMed Central

    Butcher, P D; Cevallos, A M; Carnaby, S; Alstead, E M; Swarbrick, E T; Farthing, M J

    1994-01-01

    Two Giardia isolates were axenised in vitro after recovery by duodenal aspiration from a man with hypo-gamma globulinaemia and chronic giardiasis, before and after three unsuccessful courses of metronidazole. In vitro drug sensitivity assays showed that the pretreatment isolate was sensitive to metronidazole with minimum inhibitory concentration (MIC) and dose that inhibited growth by 50% (ED50) values of 0.1 and 0.03 mumol/l, respectively. The post-treatment isolate was 20-fold more resistant (MIC and ED50 4.3 and 0.58 mumol/l, respectively). Differences between these isolates were also found in the surface protein profiles after radioiodination, metabolic labelling patterns with 35S-methionine, malic enzyme isoenzyme patterns, and by DNA fingerprinting with a M-13 bacteriophage probe. The phenotypic and genotypic differences between the pretreatment and post-treatment isolates suggest that we have isolated two different strains from the same patient and that treatment with metronidazole resulted in selection of the more resistant strain. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8307449

  17. [Quantitive variation of polysaccharides and alcohol-soluble extracts in F1 generation of Dendrobium officinale].

    PubMed

    Zhang, Xiao-Ling; Liu, Jing-Jing; Wu, Ling-Shang; Si, Jin-Ping; Guo, Ying-Ying; Yu, Jie; Wang, Lin-Hua

    2013-11-01

    Using phenol-sulfuric acid method and hot-dip method of alcohol-soluble extracts, the contents of polysaccharides and alcohol-soluble extracts in 11 F1 generations of Dendrobium officinale were determined. The results showed that the polysaccharides contents in samples collected in May and February were 32.89%-43.07% and 25.77%-35.25%, respectively, while the extracts contents were 2.81%-4.85% and 7.90%-17.40%, respectively. They were significantly different among families. The content of polysaccharides in offspring could be significantly improved by hybridization between parents with low and high polysaccharides contents, and the hybrid vigor was obvious. Cross breeding was an effective way for breeding new varieties with higher polysaccharides contents. Harvest time would significantly affect the contents of polysaccharides and alcohol-soluble extracts. The contents of polysaccharides in families collected in May were higher than those of polysaccharides in families collected in February, but the extracts content had the opposite variation. The extents of quantitative variation of polysaccharides and alcohol-soluble extracts were different among families, and each family had its own rules. It would be significant in giving full play to their role as the excellent varieties and increasing effectiveness by studying on the quantitative accumulation regularity of polysaccharides and alcohol-soluble extracts in superior families (varieties) of D. officinale to determine the best harvesting time. PMID:24494555

  18. Biogeographic discordance of molecular phylogenetic and phenotypic variation in a continental archipelago radiation of land snails

    PubMed Central

    2014-01-01

    Background In island archipelagos, where islands have experienced repeated periods of fragmentation and connection through cyclic changes in sea level, complex among-island distributions might reflect historical distributional changes or local evolution. We test the relative importance of these mechanisms in an endemic radiation of Rhagada land snails in the Dampier Archipelago, a continental archipelago off the coast of Western Australia, where ten morphospecies have complex, overlapping distributions. Results We obtained partial mtDNA sequence (COI) for 1015 snails collected from 213 locations across 30 Islands, and used Bayesian phylogenetic analysis and Analysis of Molecular Variance (AMOVA) to determine whether geography or the morphological taxonomy best explains the pattern of molecular evolution. Rather than forming distinct monophyletic groups, as would be expected if they had single, independent origins, all of the widely distributed morphospecies were polyphyletic, distributed among several well-supported clades, each of which included several morphospecies. Each mitochondrial clade had a clear, cohesive geographic distribution, together forming a series of parapatric replacements separated by narrow contact zones. AMOVA revealed further incongruence between mtDNA diversity and morphological variation within clades, as the taxonomic hypothesis always explained a low or non-significant proportion of the molecular variation. In contrast, the pattern of mtDNA evolution closely reflected contemporary and historical marine barriers. Conclusions Despite opportunities for distributional changes during periods when the islands were connected, there is no evidence that dispersal has contributed to the geographic variation of shell form at the broad scale. Based on an estimate of dispersal made previously for Rhagada, we conclude that the periods of connection have been too short in duration to allow for extensive overland dispersal or deep mitochondrial introgression. The result is a sharp and resilient phylogeographic pattern. The distribution of morphotypes among clades and distant islands is explained most simply by their parallel evolution. PMID:24393567

  19. Plastic and Heritable Components of Phenotypic Variation in Nucella lapillus: An Assessment Using Reciprocal Transplant and Common Garden Experiments

    PubMed Central

    Pascoal, Sonia; Carvalho, Gary; Creer, Simon; Rock, Jenny; Kawaii, Kei; Mendo, Sonia; Hughes, Roger

    2012-01-01

    Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F2s in the common garden partially retained characteristics of the P-generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F1s than F2s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal. PMID:22299035

  20. Plastic and heritable components of phenotypic variation in Nucella lapillus: an assessment using reciprocal transplant and common garden experiments.

    PubMed

    Pascoal, Sonia; Carvalho, Gary; Creer, Simon; Rock, Jenny; Kawaii, Kei; Mendo, Sonia; Hughes, Roger

    2012-01-01

    Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F(2)s in the common garden partially retained characteristics of the P-generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F(1)s than F(2)s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal. PMID:22299035

  1. Phenotypic variation of TTC19-deficient mitochondrial complex III deficiency: A case report and literature review.

    PubMed

    Mordaunt, Dylan A; Jolley, Alexandra; Balasubramaniam, Shanti; Thorburn, David R; Mountford, Hayley S; Compton, Alison G; Nicholl, Jillian; Manton, Nicholas; Clark, Damian; Bratkovic, Drago; Friend, Kathryn; Yu, Sui

    2015-06-01

    Isolated mitochondrial respiratory chain complex III deficiency has been described in a heterogeneous group of clinical presentations in children and adults. It has been associated with mutations in MT-CYB, the only mitochondrial DNA encoded subunit, as well as in nine nuclear genes described thus far: BCS1L, TTC19, UQCRB, UQCRQ, UQCRC2, CYC1, UQCC2, LYRM7, and UQCC3. BCS1L, TTC19, UQCC2, LYRM7, and UQCC3 are complex III assembly factors. We report on an 8-year-old girl born to consanguineous Iraqi parents presenting with slowly progressive encephalomyopathy, severe failure to thrive, significant delays in verbal and communicative skills and bilateral retinal cherry red spots on fundoscopy. SNP array identified multiple regions of homozygosity involving 7.5% of the genome. Mutations in the TTC19 gene are known to cause complex III deficiency and TTC19 was located within the regions of homozygosity. Sequencing of TTC19 revealed a homozygous nonsense mutation at exon 6 (c.937C?>?T; p.Q313X). We reviewed the phenotypes and genotypes of all 11 patients with TTC19 mutations leading to complex III deficiency (including our case). The consistent features noted are progressive neurodegeneration with Leigh-like brain MRI abnormalities. Significant variability was observed however with the age of symptom onset and rate of disease progression. The bilateral retinal cherry red spots and failure to thrive observed in our patient are unique features, which have not been described, in previously reported patients with TTC19 mutations. Interestingly, all reported TTC19 mutations are nonsense mutations. The severity of clinical manifestations however does not specifically correlate with the residual complex III enzyme activities. © 2015 Wiley Periodicals, Inc. PMID:25899669

  2. Association between allelic variation due to short tandem repeats in tRNA gene of Entamoeba histolytica and clinical phenotypes of amoebiasis.

    PubMed

    Jaiswal, Virendra; Ghoshal, Ujjala; Mittal, Balraj; Dhole, Tapan N; Ghoshal, Uday C

    2014-05-01

    Genotypes of Entamoeba histolytica (E. histolytica) may contribute clinical phenotypes of amoebiasis such as amoebic liver abscess (ALA), dysentery and asymptomatic cyst passers state. Hence, we evaluated allelic variation due to short tandem repeats (STRs) in tRNA gene of E. histolytica and clinical phenotypes of amoebiasis. Asymptomatic cyst passers (n=24), patients with dysentery (n=56) and ALA (n=107) were included. Extracted DNA from stool (dysentery, asymptomatic cyst passers) and liver aspirate was amplified using 6 E. histolytica specific tRNA-linked STRs (D-A, A-L, N-K2, R-R, S-Q, and S(TGA)-D) primers. PCR products were subjected to sequencing. Association between allelic variation and clinical phenotypes was analyzed. A total of 9 allelic variations were found in D-A, 8 in A-L, 4 in N-K2, 5 in R-R, 10 in S(TAG)-D and 7 in S-Q loci. A significant association was found between allelic variants and clinical phenotypes of amoebiasis. This study reveals that allelic variation due to short tandem repeats (STRs) in tRNA gene of E. histolytica is associated different clinical outcome of amoebiasis. PMID:24495629

  3. Comparative sex pherome biosynthesis in Thaumetopoea pityocampa and T. processionea: a rationale for the phenotypic variation in the sex pherome within the Genus Thaumetopoea

    Microsoft Academic Search

    G Villorbina; S Rodríguez; F Camps; G Fabriàs

    2003-01-01

    The female sex pheromones of the Mediterranean processionary moths (Thaumetopoea sp.) are conjugated dienes or enynes of 16 carbon atoms with the unsaturations located at C11 and C13. To investigate the biochemical basis of this phenotypic variation, the biosynthetic pathway of T. processionea sex pheromone, a diene acetate, has been elucidated and compared to that reported for the enyne-producing species

  4. Effects of environmental disturbance on phenotypic variation: an integrated assessment of canalization, developmental stability, modularity, and allometry in lizard head shape.

    PubMed

    Lazi?, Marko M; Carretero, Miguel A; Crnobrnja-Isailovi?, Jelka; Kaliontzopoulou, Antigoni

    2015-01-01

    When populations experience suboptimal conditions, the mechanisms involved in the regulation of phenotypic variation can be challenged, resulting in increased phenotypic variance. This kind of disturbance can be diagnosed by using morphometric tools to study morphological patterns at different hierarchical levels and evaluate canalization, developmental stability, integration, modularity, and allometry. We assess the effect of urbanization on phenotypic variation in the common wall lizard (Podarcis muralis) by using geometric morphometrics to assess disturbance to head shape development. The head shapes of urban lizards were more variable and less symmetric, suggesting that urban living is more likely to disturb development. Head shape variation was congruent within and across individuals, which indicated that canalization and developmental stability are two related phenomena in these organisms. Furthermore, urban lizards exhibited smaller mean head sizes, divergent size-shape allometries, and increased deviation from within-group allometric lines. This suggests that mechanisms regulating head shape allometry may also be disrupted. The integrated evaluation of several measures of developmental instability at different hierarchical levels, which provided in this case congruent results, can be a powerful methodological guide for future studies, as it enhances the detection of environmental disturbances on phenotypic variation and aids biological interpretation of the results. PMID:25560552

  5. Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I

    SciTech Connect

    Jodice, C.; Malaspina, P.; Persichetti, F.; Novelletto, A.; Terrenato, L. (Universita Tor Vergata, Rome (Italy)); Spadaro, M.; Morocutti, C. (Universita La Sapienza, Rome (Italy)); Giunti, P. (Universita La Sapienza, Rome (Italy) Institute of Neurology, London (United Kingdom)); Harding, A.E. (Institute of Neurology, London (United Kingdom)); Frontali, M. (Istituto di Medicina Sperimentale, Rome (Italy))

    1994-06-01

    Trinucleotide repeat expansion has been found in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes shows two distinct distributions, with a much wider variation among expanded chromosomes. The sex of transmitting parent plays a major role in the size distribution of expanded alleles, those with >54 repeats being transmitted by affected fathers exclusively. The data suggest that alleles with >54 repeats have a reduced chance of survival; these appear to be replaced in each generation by further expansion of alleles in the low- to medium-expanded repeat range, preferentially in male transmission. Detailed clinical follow-up of a subset of patients demonstrates significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death.

  6. Genetic variation within the Chrna7 gene modulates nicotine reward-like phenotypes in mice

    PubMed Central

    Harenza, Jo Lynne; Muldoon, Pretal P.; De Biasi, Mariella; Damaj, M. Imad; Miles, Michael F.

    2014-01-01

    Mortality from tobacco smoking remains the leading cause of preventable death in the world, yet current cessation therapies are only modestly successful, suggesting new molecular targets are needed. Genetic analysis of gene expression and behavior identified Chrna7 as potentially modulating nicotine place conditioning in the BXD panel of inbred mice. We used gene targeting and pharmacological tools to confirm the role of Chrna7 in nicotine CPP. To identify molecular events downstream of Chrna7 that may modulate nicotine preference, we performed microarray analysis of ?7 KO and WT nucleus accumbens tissue, followed by confirmation with quantitative PCR and immunoblotting. In the BXD panel, we found a putative cis eQTL for Chrna7 in nucleus accumbens that correlated inversely to nicotine CPP. We observed that gain-of-function ?7 mice did not display nicotine preference at any dose tested, while conversely, ?7 KO mice showed nicotine place preference at a dose below that routinely required to produce preference. In B6 mice, the ?7 nAChR-selective agonist, PHA-543613, dose-dependently blocked nicotine CPP, which was restored using the ?7 nAChR-selective antagonist, MLA. Our genomic studies implicated an mRNA co-expression network regulated by Chrna7 in nucleus accumbens. Mice lacking Chrna7 demonstrate increased insulin signaling in the nucleus accumbens, which may modulate nicotine place preference. Our studies provide novel targets for future work on development of more effective therapeutic approaches to counteract the rewarding properties of nicotine for smoking cessation. PMID:24289814

  7. The quantitative genetic basis of sex ratio variation in Nasonia vitripennis: a QTL study

    PubMed Central

    Pannebakker, B A; Watt, R; Knott, S A; West, S A; Shuker, D M

    2011-01-01

    Our understanding of how natural selection should shape sex allocation is perhaps more developed than for any other trait. However, this understanding is not matched by our knowledge of the genetic basis of sex allocation. Here, we examine the genetic basis of sex ratio variation in the parasitoid wasp Nasonia vitripennis, a species well known for its response to local mate competition (LMC). We identified a quantitative trait locus (QTL) for sex ratio on chromosome 2 and three weaker QTL on chromosomes 3 and 5. We tested predictions that genes associated with sex ratio should be pleiotropic for other traits by seeing if sex ratio QTL co-occurred with clutch size QTL. We found one clutch size QTL on chromosome 1, and six weaker QTL across chromosomes 2, 3 and 5, with some overlap to regions associated with sex ratio. The results suggest rather limited scope for pleiotropy between these traits. PMID:20977519

  8. Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction

    PubMed Central

    Aslibekyan, S; Jensen, MK; Campos, H; Linkletter, CD; Loucks, EB; Ordovas, JM; Deka, R; Rimm, EB; Baylin, A

    2013-01-01

    BACKGROUND/OBJECTIVES Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS MI cases (n = 1650) were matched to population-based controls (n = 1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses’ Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). RESULTS Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values = 0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value = 0.04). However, the observed associations were not replicated in independent populations. CONCLUSION Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI. PMID:22293571

  9. Segmental Quantitative MR Imaging Analysis of Diurnal Variation of Water Content in the Lumbar Intervertebral Discs

    PubMed Central

    Zhu, Tingting; Ai, Tao; Zhang, Wei; Li, Tao

    2015-01-01

    Objective To investigate the changes in water content in the lumbar intervertebral discs by quantitative T2 MR imaging in the morning after bed rest and evening after a diurnal load. Materials and Methods Twenty healthy volunteers were separately examined in the morning after bed rest and in the evening after finishing daily work. T2-mapping images were obtained and analyzed. An equally-sized rectangular region of interest (ROI) was manually placed in both, the anterior and the posterior annulus fibrosus (AF), in the outermost 20% of the disc. Three ROIs were placed in the space defined as the nucleus pulposus (NP). Repeated-measures analysis of variance and paired 2-tailed t tests were used for statistical analysis, with p < 0.05 as significantly different. Results T2 values significantly decreased from morning to evening, in the NP (anterior NP = -13.9 ms; central NP = -17.0 ms; posterior NP = -13.3 ms; all p < 0.001). Meanwhile T2 values significantly increased in the anterior AF (+2.9 ms; p = 0.025) and the posterior AF (+5.9 ms; p < 0.001). T2 values in the posterior AF showed the largest degree of variation among the 5 ROIs, but there was no statistical significance (p = 0.414). Discs with initially low T2 values in the center NP showed a smaller degree of variation in the anterior NP and in the central NP, than in discs with initially high T2 values in the center NP (10.0% vs. 16.1%, p = 0.037; 6.4% vs. 16.1%, p = 0.006, respectively). Conclusion Segmental quantitative T2 MRI provides valuable insights into physiological aspects of normal discs. PMID:25598682

  10. EFFICIENCY OF RECURRENT SELECTION BY MARKER AND PHENOTYPE FOR MULTIPLE, QUANTITATIVE YIELD COMPONENTS IN FOUR CUCUMBER POPULATIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four cucumber (Cucumus sativus L.) inbred lines were intermated then bulked maternally to create four base populations denoted as cycle 0 (i.e., Pop.1 C0, Pop.2 C0, Pop.3 C0, Pop.4 C0). Each of these populations underwent phenotypic selection (PHE; open-field evaluations), selection by marker (MAS; ...

  11. Quantitative genetics of ovariole number in Drosophila melanogaster. II. Mutational variation and genotype-environment interaction.

    PubMed Central

    Wayne, M L; Mackay, T F

    1998-01-01

    The rare alleles model of mutation-selection balance (MSB) hypothesis for the maintenance of genetic variation was evaluated for two quantitative traits, ovariole number and body size. Mutational variances (VM) for these traits, estimated from mutation accumulation lines, were 4.75 and 1.97 x 10(-4) times the environmental variance (VE), respectively. The mutation accumulation lines were studied in three environments to test for genotype x environment interaction (GEI) of new mutations; significant mutational GEI was found for both traits. Mutations for ovariole number have a quadratic relationship with competitive fitness, suggesting stabilizing selection for the trait; there is no significant correlation between mutations for body size and competitive fitness. Under MSB, the ratio of segregating genetic variance, VG, to mutational variance, VM, estimates the inverse of the selection coefficient against a heterozygote for a new mutation. Estimates of VG/VM for ovariole number and body size were both approximately 1.1 x 10(4). Thus, MSB can explain the level of variation, if mutations affecting these traits are under very weak selection, which is inconsistent with the empirical observation of stabilizing selection, or if the estimate of VM is biased downward by two orders of magnitude. GEI is a possible alternative explanation. PMID:9475732

  12. Population-Based Resequencing of APOA1 in 10,330 Individuals: Spectrum of Genetic Variation, Phenotype, and Comparison with Extreme Phenotype Approach

    PubMed Central

    Haase, Christiane L.; Frikke-Schmidt, Ruth; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne

    2012-01-01

    Rare genetic variants, identified by in-detail resequencing of loci, may contribute to complex traits. We used the apolipoprotein A-I gene (APOA1), a major high-density lipoprotein (HDL) gene, and population-based resequencing to determine the spectrum of genetic variants, the phenotypic characteristics of these variants, and how these results compared with results based on resequencing only the extremes of the apolipoprotein A-I (apoA-I) distribution. First, we resequenced APOA1 in 10,330 population-based participants in the Copenhagen City Heart Study. The spectrum and distribution of genetic variants was determined as a function of the number of individuals resequenced. Second, apoA-I and HDL cholesterol phenotypes were determined for nonsynonymous (NS) and synonymous (S) variants and were validated in the Copenhagen General Population Study (n?=?45,239). Third, observed phenotypes were compared with those predicted using an extreme phenotype approach based on the apoA-I distribution. Our results are as follows: First, population-based resequencing of APOA1 identified 40 variants of which only 7 (18%) had minor allele frequencies >1%, and most were exceedingly rare. Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis. NS variants associated with a hazard ratio of 1.72 (1.09–2.70) for myocardial infarction (MI), largely driven by A164S, a variant not associated with apoA-I or HDL cholesterol levels. Third, using the extreme apoA-I phenotype approach, NS variants correctly predicted the apoA-I phenotype observed in the population-based resequencing. However, using the extreme approach, between 79% (screening 0–1st percentile) and 21% (screening 0–20th percentile) of all variants were not identified; among these were variants previously associated with amyloidosis. Population-based resequencing of APOA1 identified a majority of rare NS variants associated with reduced apoA-1 and HDL cholesterol levels and/or predisposing to amyloidosis. In addition, NS variants associated with increased risk of MI. PMID:23209431

  13. R2OBBIE-3D, a Fast Robotic High-Resolution System for Quantitative Phenotyping of Surface Geometry and Colour-Texture.

    PubMed

    Martins, António F; Bessant, Michel; Manukyan, Liana; Milinkovitch, Michel C

    2015-01-01

    While recent imaging techniques provide insights into biological processes from the molecular to the cellular scale, phenotypes at larger scales remain poorly amenable to quantitative analyses. For example, investigations of the biophysical mechanisms generating skin morphological complexity and diversity would greatly benefit from 3D geometry and colour-texture reconstructions. Here, we report on R2OBBIE-3D, an integrated system that combines a robotic arm, a high-resolution digital colour camera, an illumination basket of high-intensity light-emitting diodes and state-of-the-art 3D-reconstruction approaches. We demonstrate that R2OBBIE generates accurate 3D models of biological objects between 1 and 100 cm, makes multiview photometric stereo scanning possible in practical processing times, and enables the capture of colour-texture and geometric resolutions better than 15 ?m without the use of magnifying lenses. R2OBBIE has the potential to greatly improve quantitative analyses of phenotypes in addition to providing multiple new applications in, e.g., biomedical science. PMID:26039509

  14. R2OBBIE-3D, a Fast Robotic High-Resolution System for Quantitative Phenotyping of Surface Geometry and Colour-Texture

    PubMed Central

    Manukyan, Liana; Milinkovitch, Michel C.

    2015-01-01

    While recent imaging techniques provide insights into biological processes from the molecular to the cellular scale, phenotypes at larger scales remain poorly amenable to quantitative analyses. For example, investigations of the biophysical mechanisms generating skin morphological complexity and diversity would greatly benefit from 3D geometry and colour-texture reconstructions. Here, we report on R2OBBIE-3D, an integrated system that combines a robotic arm, a high-resolution digital colour camera, an illumination basket of high-intensity light-emitting diodes and state-of-the-art 3D-reconstruction approaches. We demonstrate that R2OBBIE generates accurate 3D models of biological objects between 1 and 100 cm, makes multiview photometric stereo scanning possible in practical processing times, and enables the capture of colour-texture and geometric resolutions better than 15 ?m without the use of magnifying lenses. R2OBBIE has the potential to greatly improve quantitative analyses of phenotypes in addition to providing multiple new applications in, e.g., biomedical science. PMID:26039509

  15. A quantitative comparison of human HT-1080 fibrosarcoma cells and primary human dermal fibroblasts identifies a 3D migration mechanism with properties unique to the transformed phenotype.

    PubMed

    Schwartz, Michael P; Rogers, Robert E; Singh, Samir P; Lee, Justin Y; Loveland, Samuel G; Koepsel, Justin T; Witze, Eric S; Montanez-Sauri, Sara I; Sung, Kyung E; Tokuda, Emi Y; Sharma, Yasha; Everhart, Lydia M; Nguyen, Eric H; Zaman, Muhammad H; Beebe, David J; Ahn, Natalie G; Murphy, William L; Anseth, Kristi S

    2013-01-01

    Here, we describe an engineering approach to quantitatively compare migration, morphologies, and adhesion for tumorigenic human fibrosarcoma cells (HT-1080s) and primary human dermal fibroblasts (hDFs) with the aim of identifying distinguishing properties of the transformed phenotype. Relative adhesiveness was quantified using self-assembled monolayer (SAM) arrays and proteolytic 3-dimensional (3D) migration was investigated using matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) (PEG) hydrogels ("synthetic extracellular matrix" or "synthetic ECM"). In synthetic ECM, hDFs were characterized by vinculin-containing features on the tips of protrusions, multipolar morphologies, and organized actomyosin filaments. In contrast, HT-1080s were characterized by diffuse vinculin expression, pronounced ?1-integrin on the tips of protrusions, a cortically-organized F-actin cytoskeleton, and quantitatively more rounded morphologies, decreased adhesiveness, and increased directional motility compared to hDFs. Further, HT-1080s were characterized by contractility-dependent motility, pronounced blebbing, and cortical contraction waves or constriction rings, while quantified 3D motility was similar in matrices with a wide range of biochemical and biophysical properties (including collagen) despite substantial morphological changes. While HT-1080s were distinct from hDFs for each of the 2D and 3D properties investigated, several features were similar to WM239a melanoma cells, including rounded, proteolytic migration modes, cortical F-actin organization, and prominent uropod-like structures enriched with ?1-integrin, F-actin, and melanoma cell adhesion molecule (MCAM/CD146/MUC18). Importantly, many of the features observed for HT-1080s were analogous to cellular changes induced by transformation, including cell rounding, a disorganized F-actin cytoskeleton, altered organization of focal adhesion proteins, and a weakly adherent phenotype. Based on our results, we propose that HT-1080s migrate in synthetic ECM with functional properties that are a direct consequence of their transformed phenotype. PMID:24349113

  16. A Quantitative Comparison of Human HT-1080 Fibrosarcoma Cells and Primary Human Dermal Fibroblasts Identifies a 3D Migration Mechanism with Properties Unique to the Transformed Phenotype

    PubMed Central

    Schwartz, Michael P.; Rogers, Robert E.; Singh, Samir P.; Lee, Justin Y.; Loveland, Samuel G.; Koepsel, Justin T.; Witze, Eric S.; Montanez-Sauri, Sara I.; Sung, Kyung E.; Tokuda, Emi Y.; Sharma, Yasha; Everhart, Lydia M.; Nguyen, Eric H.; Zaman, Muhammad H.; Beebe, David J.; Ahn, Natalie G.; Murphy, William L.; Anseth, Kristi S.

    2013-01-01

    Here, we describe an engineering approach to quantitatively compare migration, morphologies, and adhesion for tumorigenic human fibrosarcoma cells (HT-1080s) and primary human dermal fibroblasts (hDFs) with the aim of identifying distinguishing properties of the transformed phenotype. Relative adhesiveness was quantified using self-assembled monolayer (SAM) arrays and proteolytic 3-dimensional (3D) migration was investigated using matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) (PEG) hydrogels (“synthetic extracellular matrix” or “synthetic ECM”). In synthetic ECM, hDFs were characterized by vinculin-containing features on the tips of protrusions, multipolar morphologies, and organized actomyosin filaments. In contrast, HT-1080s were characterized by diffuse vinculin expression, pronounced ?1-integrin on the tips of protrusions, a cortically-organized F-actin cytoskeleton, and quantitatively more rounded morphologies, decreased adhesiveness, and increased directional motility compared to hDFs. Further, HT-1080s were characterized by contractility-dependent motility, pronounced blebbing, and cortical contraction waves or constriction rings, while quantified 3D motility was similar in matrices with a wide range of biochemical and biophysical properties (including collagen) despite substantial morphological changes. While HT-1080s were distinct from hDFs for each of the 2D and 3D properties investigated, several features were similar to WM239a melanoma cells, including rounded, proteolytic migration modes, cortical F-actin organization, and prominent uropod-like structures enriched with ?1-integrin, F-actin, and melanoma cell adhesion molecule (MCAM/CD146/MUC18). Importantly, many of the features observed for HT-1080s were analogous to cellular changes induced by transformation, including cell rounding, a disorganized F-actin cytoskeleton, altered organization of focal adhesion proteins, and a weakly adherent phenotype. Based on our results, we propose that HT-1080s migrate in synthetic ECM with functional properties that are a direct consequence of their transformed phenotype. PMID:24349113

  17. Quantitative Assessment of Autism Symptom-related Traits in Probands and Parents: Broader Phenotype Autism Symptom Scale

    Microsoft Academic Search

    Geraldine Dawson; Annette Estes; Jeffrey Munson; Gerard Schellenberg; Raphael Bernier; Robert Abbott

    2007-01-01

    Autism susceptibility genes likely have effects on continuously distributed autism-related traits, yet few measures of such\\u000a traits exist. The Broader Phenotype Autism Symptom Scale (BPASS), developed for use with affected children and family members,\\u000a measures social motivation, social expressiveness, conversational skills, and flexibility. Based on 201 multiplex families,\\u000a psychometric data on the BPASS are reported. Adequate inter-rater reliability and internal

  18. Sex-specific quantitative trait loci contribute to normal variation in bone structure at the proximal femur in men

    Microsoft Academic Search

    Munro Peacock; Daniel L. Koller; Dongbing Lai; Siu Hui; Tatiana Foroud; Michael J. Econs

    2005-01-01

    Bone structure is an important determinant of osteoporotic fracture. In women, bone structure is highly heritable, and several quantitative trait loci (QTL) have been reported. There are few comparable data in men. This study in men aimed at establishing the heritability of bone structure at the proximal femur, identifying QTL contributing to normal variation in bone structure, and determining which

  19. Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids

    Microsoft Academic Search

    K. Duesing; G. Charpentier; M. Marre; J. Tichet; S. Hercberg; P. Froguel; F. Gibson

    2008-01-01

    Aims\\/hypothesis  In the present study, we sought to examine the evidence that LMNA variants are associated with type 2 diabetes and quantitative metabolic traits in French Europid individuals.\\u000a \\u000a \\u000a \\u000a Methods  We genotyped 24 single nucleotide polymorphisms (SNPs) spanning the LMNA gene in 3,093 case–control participants. The association between LMNA SNPs and quantitative metabolic traits was also examined in the 1,674 normoglycaemic adults who

  20. Linking the spatial scale of environmental variation and the evolution of phenotypic plasticity: selection favors adaptive plasticity in fine-grained environments.

    PubMed

    Baythavong, Brooke S

    2011-07-01

    Adaptive phenotypic plasticity and adaptive genetic differentiation enable plant lineages to maximize their fitness in response to environmental heterogeneity. The spatial scale of environmental variation relative to the average dispersal distance of a species determines whether selection will favor plasticity, local adaptation, or an intermediate strategy. Habitats where the spatial scale of environmental variation is less than the dispersal distance of a species are fine grained and should favor the expression of adaptive plasticity, while coarse-grained habitats, where environmental variation occurs on spatial scales greater than dispersal, should favor adaptive genetic differentiation. However, there is relatively little information available characterizing the link between the spatial scale of environmental variation and patterns of selection on plasticity measured in the field. I examined patterns of spatial environmental variation within a serpentine mosaic grassland and selection on an annual plant (Erodium cicutarium) within that landscape. Results indicate that serpentine soil patches are a significantly finer-grained habitat than non-serpentine patches. Additionally, selection generally favored increased plasticity on serpentine soils and diminished plasticity on non-serpentine soils. This is the first empirical example of differential selection for phenotypic plasticity in the field as a result of strong differences in the grain of environmental heterogeneity within habitats. PMID:21670579

  1. Genes and quantitative genetic variation involved with senescence in cells, organs, and the whole plant

    PubMed Central

    Pujol, Benoit

    2015-01-01

    Senescence, the deterioration of morphological, physiological, and reproductive functions with age that ends with the death of the organism, was widely studied in plants. Genes were identified that are linked to the deterioration of cells, organs and the whole plant. It is, however, unclear whether those genes are the source of age dependent deterioration or get activated to regulate such deterioration. Furthermore, it is also unclear whether such genes are active as a direct consequence of age or because they are specifically involved in some developmental stages. At the individual level, it is the relationship between quantitative genetic variation, and age that can be used to detect the genetic signature of senescence. Surprisingly, the latter approach was only scarcely applied to plants. This may be the consequence of the demanding requirements for such approaches and/or the fact that most research interest was directed toward plants that avoid senescence. Here, I review those aspects in turn and call for an integrative genetic theory of senescence in plants. Such conceptual development would have implications for the management of plant genetic resources and generate progress on fundamental questions raised by aging research. PMID:25755664

  2. Flower color changes in three Japanese hibiscus species: further quantitative variation of anthocyanin and flavonols.

    PubMed

    Shimokawa, Satoshi; Iwashina, Tsukasa; Murakami, Noriaki

    2015-03-01

    One anthocyanin and four flavonols were detected from the petals of Hibiscus hamabo, H. tiliaceus and H. glaber. They were identified as cyanidin 3-0- sambubioside, gossypetin 3-O-glucuronide-8-O-glucoside, quercetin 7-O-rutinoside, gossypetin 3-O-glucoside and gossypetin 8-O-glucuronide by UV spectra, LC-MS, acid hydrolysis and HPLC. The flavonoid composition was essentially the same among the petals ofH. hamabo, H. tiliaceus and H. glaber, and there was little quantitative variation, except for cyanidin 3-O-sambubioside, the content of which in the petals ofH. tiliaceus and H. glaber was much higher than in that of H. hamabo. Flower colors of H. tiliaceus and H. glaber change from yellow to red, and that of H. hamabo changes from yellow to orange. These changes were caused by contents of anthocyanin and flavonols, which increased after flowering of H. hamabo, H. tiliaceus and H. glaber. PMID:25924527

  3. QUANTITATIVE MAGNETIC RESONANCE IMAGE ANALYSIS VIA THE EM ALGORITHM WITH STOCHASTIC VARIATION

    PubMed Central

    Zhang, Xiaoxi; Johnson, Timothy D.; Little, Roderick J. A.; Cao, Yue

    2009-01-01

    Quantitative Magnetic Resonance Imaging (qMRI) provides researchers insight into pathological and physiological alterations of living tissue, with the help of which, researchers hope to predict (local) therapeutic efficacy early and determine optimal treatment schedule. However, the analysis of qMRI has been limited to ad-hoc heuristic methods. Our research provides a powerful statistical framework for image analysis and sheds light on future localized adaptive treatment regimes tailored to the individual’s response. We assume in an imperfect world we only observe a blurred and noisy version of the underlying pathological/physiological changes via qMRI, due to measurement errors or unpredictable influences. We use a hidden Markov Random Field to model the spatial dependence in the data and develop a maximum likelihood approach via the Expectation-Maximization algorithm with stochastic variation. An important improvement over previous work is the assessment of variability in parameter estimation, which is the valid basis for statistical inference. More importantly, we focus on the expected changes rather than image segmentation. Our research has shown that the approach is powerful in both simulation studies and on a real dataset, while quite robust in the presence of some model assumption violations. PMID:20046819

  4. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation

    PubMed Central

    Whale, Alexandra S.; Huggett, Jim F.; Cowen, Simon; Speirs, Valerie; Shaw, Jacqui; Ellison, Stephen; Foy, Carole A.; Scott, Daniel J.

    2012-01-01

    One of the benefits of Digital PCR (dPCR) is the potential for unparalleled precision enabling smaller fold change measurements. An example of an assessment that could benefit from such improved precision is the measurement of tumour-associated copy number variation (CNV) in the cell free DNA (cfDNA) fraction of patient blood plasma. To investigate the potential precision of dPCR and compare it with the established technique of quantitative PCR (qPCR), we used breast cancer cell lines to investigate HER2 gene amplification and modelled a range of different CNVs. We showed that, with equal experimental replication, dPCR could measure a smaller CNV than qPCR. As dPCR precision is directly dependent upon both the number of replicate measurements and the template concentration, we also developed a method to assist the design of dPCR experiments for measuring CNV. Using an existing model (based on Poisson and binomial distributions) to derive an expression for the variance inherent in dPCR, we produced a power calculation to define the experimental size required to reliably detect a given fold change at a given template concentration. This work will facilitate any future translation of dPCR to key diagnostic applications, such as cancer diagnostics and analysis of cfDNA. PMID:22373922

  5. Quantitative Phenotyping-Based In Vivo Chemical Screening in a Zebrafish Model of Leukemia Stem Cell Xenotransplantation

    PubMed Central

    Zhang, Beibei; Shimada, Yasuhito; Kuroyanagi, Junya; Umemoto, Noriko; Nishimura, Yuhei; Tanaka, Toshio

    2014-01-01

    Zebrafish-based chemical screening has recently emerged as a rapid and efficient method to identify important compounds that modulate specific biological processes and to test the therapeutic efficacy in disease models, including cancer. In leukemia, the ablation of leukemia stem cells (LSCs) is necessary to permanently eradicate the leukemia cell population. However, because of the very small number of LSCs in leukemia cell populations, their use in xenotransplantation studies (in vivo) and the difficulties in functionally and pathophysiologically replicating clinical conditions in cell culture experiments (in vitro), the progress of drug discovery for LSC inhibitors has been painfully slow. In this study, we developed a novel phenotype-based in vivo screening method using LSCs xenotransplanted into zebrafish. Aldehyde dehydrogenase-positive (ALDH+) cells were purified from chronic myelogenous leukemia K562 cells tagged with a fluorescent protein (Kusabira-orange) and then implanted in young zebrafish at 48 hours post-fertilization. Twenty-four hours after transplantation, the animals were treated with one of eight different therapeutic agents (imatinib, dasatinib, parthenolide, TDZD-8, arsenic trioxide, niclosamide, salinomycin, and thioridazine). Cancer cell proliferation, and cell migration were determined by high-content imaging. Of the eight compounds that were tested, all except imatinib and dasatinib selectively inhibited ALDH+ cell proliferation in zebrafish. In addition, these anti-LSC agents suppressed tumor cell migration in LSC-xenotransplants. Our approach offers a simple, rapid, and reliable in vivo screening system that facilitates the phenotype-driven discovery of drugs effective in suppressing LSCs. PMID:24454867

  6. Using molecular and quantitative variation for assessing genetic impacts on Nucella lapillus populations after local extinction and recolonization.

    PubMed

    Colson, Isabelle; Guerra-Varela, Jorge; Hughes, Roger N; Rolán-Alvarez, Emilio

    2006-06-01

    The dogwhelk Nucella lapillus is a predatory marine gastropod living on rocky shores in the North Atlantic. As with many other gastropod species, Nucella was affected by tributyltin (TBT) pollution during the 1970s and 1980s, and local populations underwent extinction. After a partial ban on TBT in the UK in 1987, vacant sites have been recolonized. Levels of genetic diversity and quantitative genetic variation in shell form were compared between recolonized sites and sites that showed continuous population at three localities across the British Isles. Overall, estimates of genetic diversity were only slightly lower in recolonized populations, suggesting that populations have recovered from previous impacts due to the relatively high levels of migration from non-impacted sites. Molecular and quantitative analyses are broadly concordant and a positive correlation was observed (although not statistically significant) between molecular and quantitative estimates of genetic diversity, indicating the potential usefulness of quantitative methods to complement molecular population genetics analyses. PMID:21396001

  7. Genetics, phosphorus availability, and herbivore-derived induction as sources of phenotypic variation of leaf volatile terpenes in a pine species

    PubMed Central

    Sampedro, Luis; Llusia, Joan; Peñuelas, Josep; Zas, Rafael

    2010-01-01

    Oleoresin produced and stored in pine tree leaves provides direct resistance to herbivores, while leaf volatile terpenes (LVT) in the resin are also powerful airborne infochemicals. Resin concentration and profile show considerable spatial and temporal phenotypic variation within and among pine populations. LVT biochemistry is known to be under genetic control, and although LVT should be plastic to diverse abiotic and biotic environmental factors such as nutrient availability and herbivore attack, little is known about their relative contributions and interactive effects. The aim of this paper was to clarify whether reduced phosphorus availability could increase the LVT concentration and affect the expression of herbivore-derived induced defences, and how plasticity would contribute to the phenotypic variation of LVT. The constitutive and methyl-jasmonate (MeJa) induced LVT concentration and profile were analysed in 17 half-sib Pinus pinaster families growing under two levels of P-availability (complete and P-limited fertilization). Individual terpene concentrations showed large additive genetic variation, which was more pronounced in the control than in MeJa-induced pines. MeJa application did not affect the LVT concentration, but significantly modified the LVT profile by depleting the ?-pinene content and reducing the sesquiterpene fraction. Low P-availability strongly reduced plant growth and foliar nutrient concentrations, but did not affect LVT concentration and profile, and did not interact with MeJa-induction. Results indicate a strong homeostasis of LVT concentration to P-availability, and minor changes in the LVT profile due to MeJa-induction. Genetic variation appears to be the main source of phenotypic variation affecting the LVT concentration in this pine species. PMID:20952630

  8. Limited phylogeographic signal in sex-linked and autosomal loci despite geographically, ecologically, and phenotypically concordant structure of mtDNA variation in the Holarctic avian genus Eremophila.

    PubMed

    Drovetski, Sergei V; Rakovi?, Marko; Semenov, Georgy; Fadeev, Igor V; Red'kin, Yaroslav A

    2014-01-01

    Phylogeographic studies of Holarctic birds are challenging because they involve vast geographic scale, complex glacial history, extensive phenotypic variation, and heterogeneous taxonomic treatment across countries, all of which require large sample sizes. Knowledge about the quality of phylogeographic information provided by different loci is crucial for study design. We use sequences of one mtDNA gene, one sex-linked intron, and one autosomal intron to elucidate large scale phylogeographic patterns in the Holarctic lark genus Eremophila. The mtDNA ND2 gene identified six geographically, ecologically, and phenotypically concordant clades in the Palearctic that diverged in the Early-Middle Pleistocene and suggested paraphyly of the horned lark (E. alpestris) with respect to the Temminck's lark (E. bilopha). In the Nearctic, ND2 identified five subclades which diverged in the Late Pleistocene. They overlapped geographically and were not concordant phenotypically or ecologically. Nuclear alleles provided little information on geographic structuring of genetic variation in horned larks beyond supporting the monophyly of Eremophila and paraphyly of the horned lark. Multilocus species trees based on two nuclear or all three loci provided poor support for haplogroups identified by mtDNA. The node ages calculated using mtDNA were consistent with the available paleontological data, whereas individual nuclear loci and multilocus species trees appeared to underestimate node ages. We argue that mtDNA is capable of discovering independent evolutionary units within avian taxa and can provide a reasonable phylogeographic hypothesis when geographic scale, geologic history, and phenotypic variation in the study system are too complex for proposing reasonable a priori hypotheses required for multilocus methods. Finally, we suggest splitting the currently recognized horned lark into five Palearctic and one Nearctic species. PMID:24498139

  9. Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

    PubMed Central

    Krausz, Csilla; Giachini, Claudia; Xue, Yali; O’Brya, Moira K.; Gromoll, Joerg; Rajpert-de Meyts, Ewa; Oliva, Rafael; Aknin-Seifer, Isabelle; Erdei, Edit; Jorgensen, Niels; Simoni, Manuela; Ballescà, José Luis; Levy, Rachel; Balercia, Giancarlo; Piomboni, Paola; Nieschlag, Eberhard; Forti, Gianni; McLachlan, Rob; Tyler-Smith, Chris

    2009-01-01

    Background Previous studies have compared sperm phenotypes between men with partial [1] deletions within the AZFc region of the Y chromosome with non-carriers, with variable results. Here, we have investigated a separate question, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. We set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range. Results We assembled a collection of 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia, and characterized the DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup. Although our study had good power to detect factors that accounted for ?5.5% of the variation in sperm concentration, no such factor was detected. A negative effect of gr/gr deletions followed by b2/b4 duplication was observed within the normospermic group, which remains to be further explored in a larger study population. Finally, we observed significant geographical differences in the frequency of different subtypes of gr/gr deletions which may have relevance for the interpretation of case control studies dealing with admixed populations. Conclusions We conclude that the phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background. PMID:18782837

  10. Skin Expression of Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Sibling Patients with Recessive Dystrophic Epidermolysis and Intrafamilial Phenotypic Variation

    Microsoft Academic Search

    Christine Bodemer; Sylvie Igondjo Tchen; Sabah Ghomrasseni; Sylvie Séguier; Frédérick Gaultier; Sylvie Fraitag; Yves de Prost; Gaston Godeau

    2003-01-01

    A number of COL7A1 mutations have now been reported in recessive dystrophic epidermolysis bullosa patients, and the analysis of phenotype?genotype correlations showed evidence for interfamilial and intrafamilial phenotypic variability, occurring for the same mutation. Collagenase and stromelysin activities have been found to be overexpressed in skin cultures of some recessive dystrophic epidermolysis bullosa patients, and tissue destruction in the disease

  11. Copy Number Variations Burden on miRNA Genes Reveals Layers of Complexities Involved in the Regulation of Pathways and Phenotypic Expression

    PubMed Central

    Veerappa, Avinash M.; Nachappa, Somanna Ajjamada; Prashali, Nelchi; Yadav, Sangeetha Nuggehalli; Srikanta, Manjula Arsikere; Manjegowda, Dinesh S.; Seshachalam, Keshava B.; Ramachandra, Nallur B.

    2014-01-01

    MicroRNAs are involved in post-transcriptional down-regulation of gene expression. Variations in miRNA genes can severely affect downstream-regulated genes and their pathways. However, population-specific burden of CNVs on miRNA genes and the complexities created towards the phenotype is not known. From a total of 44109 CNVs investigated from 1715 individuals across 12 populations using high-throughput arrays, 4007 miRNA-CNVs (?9%) consisting 6542 (?5%) miRNA genes with a total of 333 (?5%) singleton miRNA genes were identified. We found miRNA-CNVs across the genomes of individuals showing multiple hits in many targets, co-regulated under the same pathway. This study proposes four mechanisms unraveling the many complexities in miRNA genes, targets and co-regulated miRNA genes towards establishment of phenotypic diversity. PMID:24587348

  12. Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects.

    PubMed

    Byars, Sean G; Stearns, Stephen C; Boomsma, Jacobus J

    2014-11-01

    Opposite phenotypic and behavioural traits associated with copy number variation and disruptions to imprinted genes with parent-of-origin effects have led to the hypothesis that autism and schizophrenia share molecular risk factors and pathogenic mechanisms, but a direct phenotypic comparison of how their risks covary has not been attempted. Here, we use health registry data collected on Denmark's roughly 5 million residents between 1978 and 2009 to detect opposing risks of autism and schizophrenia depending on normal variation (mean ± 1 s.d.) in adjusted birth size, which we use as a proxy for diametric gene-dosage variation in utero. Above-average-sized babies (weight, 3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for autism spectrum (AS) and significantly lower risk for schizophrenia spectrum (SS) disorders. By contrast, below-average-sized babies (2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and significantly higher risk for SS disorders. This is the first study directly comparing autism and schizophrenia risks in the same population, and provides the first large-scale empirical support for the hypothesis that diametric gene-dosage effects contribute to these disorders. Only the kinship theory of genomic imprinting predicts the opposing risk patterns that we discovered, suggesting that molecular research on mental disease risk would benefit from considering evolutionary theory. PMID:25232142

  13. Quantitation of cotton fibre-quality variations arising from boll and plant growth environments

    Microsoft Academic Search

    Judith M. Bradow; Philip J. Bauer; Oscar Hinojosa; Gretchen Sassenrath-Cole

    1997-01-01

    Crop growth simulation models used to manage cultural inputs and to improve yields of cotton, Gossypium hirsutum L., do not address fibre quality, a major determinant of cotton fibre price and end-use. Fibre maturation simulations require rapid, reproducible methods for fibre quality quantitation at the boll or locule level. Combination of fibre quality mapping by fruiting site with quality quantitation

  14. Genetic Markers and Quantitative Genetic Variation in Medicago truncutula (Leguminosae): A Comparative Analysis of Population Structure

    Microsoft Academic Search

    Isabelle Bonnin; Jean-Marie Prosperi; Isabelle Olivierit

    Two populations of the selfing annual Medicago truncatula Gaertn. (Leguminoseae), each subdivided into three subpopulations, were studied for both metric traits (quantitative characters) and genetic markers (random amplified polymorphic DNA and one morphological, single-locus marker). Hierarchical analyses of variance components show that (1) populations are more differentiated for quantitative characters than for marker loci, (2) the contribution of both within

  15. Seasonal variation in pectoralis muscle and heart myostatin and tolloid-like proteinases in small birds: a regulatory role for seasonal phenotypic flexibility?

    PubMed

    Swanson, David L; King, Marisa O; Harmon, Erin

    2014-02-01

    Seasonally variable environments produce seasonal phenotypes in small birds such that winter birds have higher thermogenic capacities and pectoralis and heart masses. One potential regulator of these seasonal phenotypes is myostatin, a muscle growth inhibitor, which may be downregulated under conditions promoting increased energy demand. We examined summer-to-winter variation in skeletal muscle and heart masses and used qPCR and Western blots to measure levels of myostatin and its metalloproteinase activators TLL-1 and TLL-2 for two small temperate-zone resident birds, American goldfinches (Spinus tristis) and black-capped chickadees (Poecile atricapillus). Winter pectoralis and heart masses were significantly greater than in summer for American goldfinches. Neither myostatin expression nor protein levels differed significantly between seasons for goldfinch pectoralis. However, myostatin levels in goldfinch heart were significantly greater in summer than in winter, although heart myostatin expression was seasonally stable. In addition, expression of both metalloproteinase activators was greater in summer than in winter goldfinches for both pectoralis and heart, significantly so except for heart TLL-2 (P = 0.083). Black-capped chickadees showed no significant seasonal variation in muscle or heart masses. Seasonal patterns of pectoralis and heart expression and/or protein levels for myostatin and its metalloproteinase activators in chickadees showed no consistent seasonal trends, which may help explain the absence of significant seasonal variation in muscle or heart masses for chickadees in this study. These data are partially consistent with a regulatory role for myostatin, and especially myostatin processing capacity, in mediating seasonal metabolic phenotypes of small birds. PMID:24395519

  16. Phenotypic variation and leaf fluctuating asymmetry in isolated populations of an endangered dwarf birch Betula ovalifolia in Hokkaido, Japan

    Microsoft Academic Search

    TERUYOSHI NAGAMITSU; TAKAYUKI KAWAHARA; MAYUKO HOTTA

    2004-01-01

    Betula ovalifolia is an endangered tetraploid that is restricted to two isolated sites, Betsukai and Sarabetsu, in Hokkaido, Japan. Among 50 ramets sampled along transect(s) in the each site, 45 genets in Betsukai and 49 in Sarabetsu were discriminated by simple sequence repeat (SSR) phenotypes. Multivariate patterns in seven measurements for leaf morphology and frequency distributions of fragment lengths in

  17. Phenotyping of an in vitro model of ischemic penumbra by iTRAQ-based shotgun quantitative proteomics.

    PubMed

    Datta, Arnab; Park, Jung Eun; Li, Xin; Zhang, Huoming; Ho, Zhi Shan; Heese, Klaus; Lim, Sai Kiang; Tam, James P; Sze, Siu Kwan

    2010-01-01

    Cerebral ischemia is a major cause of death and long-term disability worldwide. Ischemic penumbra, the electrically silent but metabolically viable perifocal brain tissue, is the target for the much elusive stroke therapy. To characterize the molecular events of the dynamic penumbra, we applied an iTRAQ-based shotgun proteomic approach in an in vitro neuronal model, using the rat B104 neuroblastoma cell line. Various functional and cytometric assays were performed to establish the relevant time-point and conditions for ischemia to recapitulate the pathology of the penumbra. Two replicate iTRAQ experiments identified 1796 and 1566 proteins, respectively (quantitative proteomics for the elucidation of pathophysiology and the discovery of novel therapeutic targets in the field of neuroproteomics. PMID:19916522

  18. Introgression study reveals two quantitative trait loci involved in interspecific variation in memory retention among Nasonia wasp species.

    PubMed

    Hoedjes, K M; Smid, H M; Vet, L E M; Werren, J H

    2014-12-01

    Genes involved in the process of memory formation have been studied intensively in model organisms; however, little is known about the mechanisms that are responsible for natural variation in memory dynamics. There is substantial variation in memory retention among closely related species in the parasitic wasp genus Nasonia. After a single olfactory conditioning trial, N. vitripennis consolidates long-term memory that lasts at least 6 days. Memory of the closely related species N. giraulti is present at 24 h but is lost within 2 days after a single trial. The genetic basis of this interspecific difference in memory retention was studied in a backcrossing experiment in which the phenotype of N. giraulti was selected for in the background of N. vitripennis for up to five generations. A genotyping microarray revealed five regions that were retained in wasps with decreased memory retention. Independent introgressions of individual candidate regions were created using linked molecular markers and tested for memory retention. One region on chromosome 1 (spanning ?5.8 cM) and another on chromosome 5 (spanning ?25.6 cM) resulted in decreased memory after 72 h, without affecting 24-h-memory retention. This phenotype was observed in both heterozygous and homozygous individuals. Transcription factor CCAAT/enhancer-binding protein and a dopamine receptor, both with a known function in memory formation, are within these genomic regions and are candidates for the regulation of memory retention. Concluding, this study demonstrates a powerful approach to study variation in memory retention and provides a basis for future research on its genetic basis. PMID:25052416

  19. Molecular dissection of phenotypic variation between Gossypium hirsutum and Gossypium barbadense (cotton) by a backcross-self approach: III. Fiber length

    Microsoft Academic Search

    Peng W. Chee; Xavier Draye; Chun-Xiao Jiang; Laura Decanini; Terrie A. Delmonte; Robert Bredhauer; C. Wayne Smith; Andrew H. Paterson

    2005-01-01

    A backcross-self population from a cross between Gossypium hirsutum and G. barbadense was used to dissect the molecular basis of genetic variation governing 15 parameters that reflect fiber length. Applying a detailed restriction fragment length polymorphism (RFLP) map to 3,662 BC3F2 plants from 24 independently derived BC3 families, we detected 28, nine, and eight quantitative trait loci (QTLs) for fiber

  20. Challenges in genetic counseling because of intra-familial phenotypic variation of oral-facial-digital syndrome type 1.

    PubMed

    Shimojima, Keiko; Shimada, Shino; Sugawara, Midori; Yoshikawa, Naomi; Niijima, Shinichi; Urao, Masahiko; Yamamoto, Toshiyuki

    2013-12-01

    Oral-facial-digital syndrome type 1 (OFD1; MIM 311200) is characterized by multiple anomalies of the oral cavity, face and digits. We report a family with OFD1, where two female siblings and their mother shared the same mutation of the responsible gene (OFD1) c.1193_1196delAATC. Phenotypic variability was observed among them; the mother showed minimal features of OFD1, whereas her two daughters showed partial features and the full spectrum of OFD1, respectively. Thus, OFD1 was suspected only after a health check-up during pregnancy of the second patient showing fetal brain anomaly and maternal polycystic kidney. For these reasons, there was a delay in the recognition of OFD1 in this family. Patients with OFD1 show phenotypic variability, which poses challenges for genetic counseling. PMID:24712474

  1. Variation in psychosis gene ZNF804A is associated with a refined schizotypy phenotype but not neurocognitive performance in a large young male population.

    PubMed

    Stefanis, Nicholas C; Hatzimanolis, Alex; Avramopoulos, Dimitrios; Smyrnis, Nikolaos; Evdokimidis, Ioannis; Stefanis, Costas N; Weinberger, Daniel R; Straub, Richard E

    2013-11-01

    Genetic variability within the ZNF804A gene has been recently found to be associated with schizophrenia and bipolar disorder, although the pathways by which this gene may confer risk remain largely unknown. We set out to investigate whether common ZNF804A variants affect psychosis-related intermediate phenotypes such as cognitive performance dependent on prefrontal and frontotemporal brain function, schizotypal traits, and attenuated psychotic experiences in a large young male population. Association analyses were performed using all 4 available self-rated schizotypy questionnaires and cognitive data retrospectively drawn from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS). DNA samples from 1507 healthy young men undergoing induction to military training were genotyped for 4 previously studied polymorphic markers in the ZNF804A gene locus. Single-marker analysis revealed significant associations between 2 recently identified candidate schizophrenia susceptibility variants (rs1344706 and rs7597593) and a refined positive schizotypy phenotype characterized primarily by self-rated paranoia/ideas of reference. Nominal associations were noted with all positive, but not negative, schizotypy related factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype level. No significant associations were noted with central indexes of sustained attention or working memory performance. In this study, ZNF804A variation was associated with a population-based self-rated schizotypy phenotype previously suggested to preferentially reflect genetic liability to psychosis and defined by a tendency to misinterpret otherwise neutral social cues and perceptual experiences in one's immediate environment, as personally relevant and significant information. This suggests a novel route by which schizophrenia-implicated ZNF804A genetic variation may confer risk to clinical psychosis at the general population level. PMID:23155182

  2. Influence of dominance, leptokurtosis and pleiotropy of deleterious mutations on quantitative genetic variation at mutation-selection balance.

    PubMed Central

    Zhang, Xu-Sheng; Wang, Jinliang; Hill, William G

    2004-01-01

    In models of maintenance of genetic variance (V (G)) it has often been assumed that mutant alleles act additively. However, experimental data show that the dominance coefficient varies among mutant alleles and those of large effect tend to be recessive. On the basis of empirical knowledge of mutations, a joint-effect model of pleiotropic and real stabilizing selection that includes dominance is constructed and analyzed. It is shown that dominance can dramatically alter the prediction of equilibrium V (G). Analysis indicates that for the situations where mutations are more recessive for fitness than for a quantitative trait, as supported by the available data, the joint-effect model predicts a significantly higher V (G) than does an additive model. Importantly, for what seem to be realistic distributions of mutational effects (i.e., many mutants may not affect the quantitative trait substantially but are likely to affect fitness), the observed high levels of genetic variation in the quantitative trait under strong apparent stabilizing selection can be generated. This investigation supports the hypothesis that most V (G) comes from the alleles nearly neutral for fitness in heterozygotes while apparent stabilizing selection is contributed mainly by the alleles of large effect on the quantitative trait. Thus considerations of dominance coefficients of mutations lend further support to our previous conclusion that mutation-selection balance is a plausible mechanism of the maintenance of the genetic variance in natural populations. PMID:15020447

  3. Interacting personalities: behavioural ecology meets quantitative genetics.

    PubMed

    Dingemanse, Niels J; Araya-Ajoy, Yimen G

    2015-02-01

    Behavioural ecologists increasingly study behavioural variation within and among individuals in conjunction, thereby integrating research on phenotypic plasticity and animal personality within a single adaptive framework. Interactions between individuals (cf. social environments) constitute a major causative factor of behavioural variation at both of these hierarchical levels. Social interactions give rise to complex 'interactive phenotypes' and group-level emergent properties. This type of phenotype has intriguing evolutionary implications, warranting a cohesive framework for its study. We detail here how a reaction-norm framework might be applied to usefully integrate social environment theory developed in behavioural ecology and quantitative genetics. The proposed emergent framework facilitates firm integration of social environments in adaptive research on phenotypic characters that vary within and among individuals. PMID:25543234

  4. One quantitative trait locus for intra-and interspecific variation in a sex pheromone

    E-print Network

    Nachman, Michael

    - and interspecific genetic variation (Wittkopp et al. 2008, 2009; Chenoweth & McGuigan 2010). At one extreme are distinct, at least in Drosophila species, as shown by two recent reviews (Arbuthnott 2009; Chenoweth & McGuigan

  5. Validation and Estimation of Additive Genetic Variation Associated with DNA Tests for Quantitative Beef Cattle Traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The U.S. National Beef Cattle Evaluation Consortium (NBCEC) has been involved in the validation of commercial DNA tests for quantitative beef quality traits since their first appearance on the U.S. market in the early 2000s. The NBCEC Advisory Council initially requested that the NBCEC set up a syst...

  6. Multivariate pattern of quantitative trait variation in triploid banana and plantain cultivars

    Microsoft Academic Search

    Julian O. Osuji; Bosa E. Okoli; Dirk Vuylsteke; Rodomiro Ortiz

    1997-01-01

    Plantains and bananas (Musa spp. L.) are inter- or intraspecific triploid hybrids derived from crosses between M. acuminata Colla. (A genome) and M. balbisiana Colla. (B genome). Cultivars have been assigned to different taxonomic groups (AA, BB, AAA, AAB, ABB, etc.) based on morphological qualitative descriptors. Principal component analysis of 15 quantitative traits was carried out to establish a more

  7. Phenotypic variation and spatial structure of secondary chemistry in a natural population of a tropical tree species

    E-print Network

    Bermingham, Eldredge

    (Berenbaum and Zangerl 1992), developmental (Bowers and Stamp 1993) and environmental (Agrell et al. 2000) sources of variation. Thus, the age structure, environ- mental heterogeneity and limits in gene flow

  8. 3D geometry and quantitative variation of the cervico-thoracic region in Crocodylia.

    PubMed

    Chamero, Beatriz; Buscalioni, Angela D; Marugán-Lobón, Jesús; Sarris, Ioannis

    2014-07-01

    This study aims to interpret the axial patterning of the crocodylian neck, and to find a potential taxonomic signal that corresponds to vertebral position. Morphological variation in the cervico-thoracic vertebrae is compared in fifteen different crocodylian species using 3D geometric morphometric methods. Multivariate analysis indicated that the pattern of intracolumnar variation was a gradual change in shape of the vertebral series (at the parapophyses, diapophyses, prezygapohyses, and postzygapohyses), in the cervical (C3 to C9) and dorsal (D1-D2) regions which was quite conservative among the crocodylians studied. In spite of this, we also found that intracolumnar shape variation allowed differentiation between two sub regions of the crocodylian neck. Growth is subtly correlated with vertebral shape variation, predicting changes in both the vertebral centrum and the neural spine. Interestingly, the allometric scaling for the pooled sample is equivalently shared by each vertebra studied. However, there were significant taxonomic differences, both in the average shape of the entire neck configuration (regional variation) and by shape variation at each vertebral position (positional variation) among the necks. The average neck vertebra of crocodylids is characterized by a relatively cranio-caudally short neural arch, whereby the spine is relatively longer and pointed orthogonal to the frontal plane. Conversely, the average vertebra in alligatorids has cranio-caudally longer neural spine and arch, with a relatively (dorso-ventrally) shorter spine. At each vertebral position there are significant differences between alligatorids and crocodylids. We discuss that the delayed timing of neurocentral fusion in Alligatoridae possibly explains the observed taxonomic differences. PMID:24753482

  9. Quantitative mapping of pore fraction variations in silicon nitride using an ultrasonic contact scan technique

    NASA Technical Reports Server (NTRS)

    Roth, Don J.; Kiser, James D.; Swickard, Suzanne M.; Szatmary, Steven A.; Kerwin, David P.

    1993-01-01

    An ultrasonic scan procedure using the pulse-echo contact configuration was employed to obtain maps of pore fraction variations in sintered silicon nitride samples in terms of ultrasonic material properties. Ultrasonic velocity, attenuation coefficient, and reflection coefficient images were obtained simultaneously over a broad band of frequencies (e.g., 30 to 110 MHz) by using spectroscopic analysis. Liquid and membrane (dry) coupling techniques and longitudinal and shear-wave energies were used. The major results include the following: Ultrasonic velocity (longitudinal and shear wave) images revealed and correlated with the extent of average through-thickness pore fraction variations in the silicon nitride disks. Attenuation coefficient images revealed pore fraction nonuniformity due to the scattering that occurred at boundaries between regions of high and low pore fraction. Velocity and attenuation coefficient images were each nearly identical for machined and polished disks, making the method readily applicable to machined materials. Velocity images were similar for wet and membrane coupling. Maps of apparent Poisson's ratio constructed from longitudinal and shear-wave velocities quantified Poisson's ratio variations across a silicon nitride disk. Thermal wave images of a disk indicated transient thermal behavior variations that correlated with observed variations in pore fraction and velocity and attenuation coefficients.

  10. Phenotypic convergence along a gradient of predation risk.

    PubMed

    Dennis, S R; Carter, Mauricio J; Hentley, W T; Beckerman, A P

    2011-06-01

    A long-standing question in ecology is whether phenotypic plasticity, rather than selection per se, is responsible for phenotypic variation among populations. Plasticity can increase or decrease variation, but most previous studies have been limited to single populations, single traits and a small number of environments assessed using univariate reaction norms. Here, examining two genetically distinct populations of Daphnia pulex with different predation histories, we quantified predator-induced plasticity among 11 traits along a fine-scale gradient of predation risk by a predator (Chaoborus) common to both populations. We test the hypothesis that plasticity can be responsible for convergence in phenotypes among different populations by experimentally characterizing multivariate reaction norms with phenotypic trajectory analysis (PTA). Univariate analyses showed that all genotypes increased age and size at maturity, and invested in defensive spikes (neckteeth), but failed to quantitatively describe whole-organism response. In contrast, PTA quantified and qualified the phenotypic strategy the organism mobilized against the selection pressure. We demonstrate, at the whole-organism level, that the two populations occupy different areas of phenotypic space in the absence of predation but converge in phenotypic space as predation threat increases. PMID:21084350

  11. Variation

    Microsoft Academic Search

    Duane S. Boning; Karthik Balakrishnan; Hong Cai; Nigel Drego; Ali Farahanchi; Karen M. Gettings; Lim Daihyun; Ajay Somani; Hayden Taylor; Daniel Truque; Xie Xiaolin

    2008-01-01

    Variation afflicts the design, manufacture, and operation of integrated circuits. Techniques and tools are needed in three areas to address variation: statistical metrology, advanced process control, and design for manufacturability. First, statistical metrology seeks to characterize and model variations and their sources. Advanced metrology helps to understand geometric and material property variations, while variation test structures and test circuits enable

  12. GATA6 reporter gene reveals myocardial phenotypic heterogeneity that is related to variations in gap junction coupling

    PubMed Central

    Rémond, Mathieu C.; Iaffaldano, Grazia; O'Quinn, Michael P.; Mezentseva, Nadejda V.; Garcia, Victor; Harris, Brett S.; Gourdie, Robert G.; Eisenberg, Carol A.

    2011-01-01

    This study examined transgenic mice whose expression of a ?-galactosidase (lacZ) reporter is driven by a GATA6 gene enhancer. Previous investigations established that transcription of the transgene was associated with precardiac mesoderm and primary heart tube myocardium, which decreased progressively, so that its expression was no longer observed within ventricular myocardium by midgestation. Expression of this reporter in the adult was investigated for insights into myocyte homeostasis and cardiovascular biology. Morphometric analysis determined that <1% of myocytes, often found in small clusters, express this GATA6-associated reporter in the adult heart. LacZ expression was also found in the ascending aorta. Myocardial expression of the transgene was not associated with a proliferative phenotype or new myocyte formation, as lacZ-positive myocytes neither labeled with cell division markers nor following 5-bromodeoxyuridine pulse-chase experimentation. Despite exhibiting normal adherens junctions, these myocytes appeared to exhibit decreased connexin 43 gap junctions. Treatment with the gap junctional blocker heptanol both in vivo and in culture elevated myocardial ?-galactosidase activity, suggesting that deficient gap junctional communication underlies expression of the transgenic reporter. LacZ expression within the myocardium was also enhanced in response to cryoinjury and isoproterenol-induced hypertrophy. These results reveal a previously uncharacterized phenotypic heterogeneity in the myocardium and suggest that decreased gap junctional coupling leads to induction of a signaling pathway that utilizes a unique GATA6 enhancer. Upregulation of lacZ reporter gene expression following cardiac injury indicates this transgenic mouse may serve as a model for examining the transition of the heart from healthy to pathological states. PMID:21908788

  13. Patterns of association between genetic variability in apolipoprotein (apo) B, apo AI-CIII-AIV, and cholesterol ester transfer protein gene regions and quantitative variation in lipid and lipoprotein traits: influence of gender and exogenous hormones.

    PubMed Central

    Kessling, A; Ouellette, S; Bouffard, O; Chamberland, A; Bétard, C; Selinger, E; Xhignesse, M; Lussier-Cacan, S; Davignon, J

    1992-01-01

    Patterns of RFLP association were studied, to identify gene regions influencing quantitative variation in lipid and lipoprotein traits (coronary artery disease [CAD] risk factors or metabolically related traits). Subjects (118 female and 229 male; age 20-59 years) were selected for health. Multiple RFLPs were used to sample variability in regions around genes for apolipoprotein (apo) B (restriction enzymes HincII, PvuII, EcoRI, and XbaI), apo AI-CIII-AIV (BamHI, XmnI, TaqI, PstI, SstI, and PvuII) and cholesterol ester transfer protein (TaqI). Separate analyses were done by gender. The sample was truncated at mean +/- 4 SD, to remove extreme outliers. There was no significant gender difference in RFLP genotype frequency distribution. After trait-level adjustment to maximize removal of concomitant variability, analysis of variance was used to estimate the percentage trait phenotypic variance explained by measured variability in the gene regions studied. Fewer gene regions were involved in men, with less influence on quantitative trait variation than in women, in whom hormone use affected association patterns. Gender differences imply that pooling genders or adjusting data for gender effects removes genetic information and should be avoided. The association patterns show that variability around the candidate genes modulates trait levels: the genes are contributors to the genetics of CAD risk variables in a healthy sample. PMID:1346081

  14. Conflicting selection from fire and seed predation drives fine-scaled phenotypic variation in a widespread North American conifer.

    PubMed

    Talluto, Matthew V; Benkman, Craig W

    2014-07-01

    Recent work has demonstrated that evolutionary processes shape ecological dynamics on relatively short timescales (eco-evolutionary dynamics), but demonstrating these effects at large spatial scales in natural landscapes has proven difficult. We used empirical studies and modeling to investigate how selective pressures from fire and predispersal seed predation affect the evolution of serotiny, an ecologically important trait. Serotiny is a highly heritable key reproductive trait in Rocky Mountain lodgepole pine (Pinus contorta subsp. latifolia), a conifer that dominates millions of hectares in western North America. In these forests, the frequency of serotiny determines postfire seedling density with corresponding community- and ecosystem-level effects. We found that serotinous individuals have a selective advantage at high fire frequencies and low predation pressure; however, very high seed predation shifted the selective advantage to nonserotinous individuals even at high fire frequencies. Simulation modeling suggests that spatial variation in the frequency of serotiny results from heterogeneity in these two selective agents. These results, combined with previous findings showing a negative association between the density of seed predators and the frequency of serotiny at both landscape and continental scales, demonstrate that contemporary patterns in serotiny reflect an evolutionary response to conflicting selection pressures from fire and seed predation. Thus, we show that variation in the frequency of a heritable polygenic trait depends on spatial variation in two dominant selective agents, and, importantly, the effects of the local trait variation propagate with profound consequences to the structure and function of communities and ecosystems across a large landscape. PMID:24979772

  15. Conflicting selection from fire and seed predation drives fine-scaled phenotypic variation in a widespread North American conifer

    PubMed Central

    Talluto, Matthew V.; Benkman, Craig W.

    2014-01-01

    Recent work has demonstrated that evolutionary processes shape ecological dynamics on relatively short timescales (eco-evolutionary dynamics), but demonstrating these effects at large spatial scales in natural landscapes has proven difficult. We used empirical studies and modeling to investigate how selective pressures from fire and predispersal seed predation affect the evolution of serotiny, an ecologically important trait. Serotiny is a highly heritable key reproductive trait in Rocky Mountain lodgepole pine (Pinus contorta subsp. latifolia), a conifer that dominates millions of hectares in western North America. In these forests, the frequency of serotiny determines postfire seedling density with corresponding community- and ecosystem-level effects. We found that serotinous individuals have a selective advantage at high fire frequencies and low predation pressure; however, very high seed predation shifted the selective advantage to nonserotinous individuals even at high fire frequencies. Simulation modeling suggests that spatial variation in the frequency of serotiny results from heterogeneity in these two selective agents. These results, combined with previous findings showing a negative association between the density of seed predators and the frequency of serotiny at both landscape and continental scales, demonstrate that contemporary patterns in serotiny reflect an evolutionary response to conflicting selection pressures from fire and seed predation. Thus, we show that variation in the frequency of a heritable polygenic trait depends on spatial variation in two dominant selective agents, and, importantly, the effects of the local trait variation propagate with profound consequences to the structure and function of communities and ecosystems across a large landscape. PMID:24979772

  16. Genetic and Phenotypic Variation of Foot-and-Mouth Disease Virus during Serial Passages in a Natural Host

    Microsoft Academic Search

    C. Carrillo; Z. Lu; M. V. Borca; A. Vagnozzi; G. F. Kutish; D. L. Rock

    2007-01-01

    Foot-and-mouth disease virus (FMDV), like other RNA viruses, exhibits high mutation rates during repli- cation that have been suggested to be of adaptive value. However, even though genetic variation in RNA viruses and, more specifically, FMDV has been extensively examined during virus replication in a wide variety of in vitro cell cultures, very little is known regarding the generation and

  17. Single Nucleotide Variants in Transcription Factors Associate More Tightly with Phenotype than with Gene Expression

    PubMed Central

    Sudarsanam, Priya; Cohen, Barak A.

    2014-01-01

    Mapping the polymorphisms responsible for variation in gene expression, known as Expression Quantitative Trait Loci (eQTL), is a common strategy for investigating the molecular basis of disease. Despite numerous eQTL studies, the relationship between the explanatory power of variants on gene expression versus their power to explain ultimate phenotypes remains to be clarified. We addressed this question using four naturally occurring Quantitative Trait Nucleotides (QTN) in three transcription factors that affect sporulation efficiency in wild strains of the yeast, Saccharomyces cerevisiae. We compared the ability of these QTN to explain the variation in both gene expression and sporulation efficiency. We find that the amount of gene expression variation explained by the sporulation QTN is not predictive of the amount of phenotypic variation explained. The QTN are responsible for 98% of the phenotypic variation in our strains but the median gene expression variation explained is only 49%. The alleles that are responsible for most of the variation in sporulation efficiency do not explain most of the variation in gene expression. The balance between the main effects and gene-gene interactions on gene expression variation is not the same as on sporulation efficiency. Finally, we show that nucleotide variants in the same transcription factor explain the expression variation of different sets of target genes depending on whether the variant alters the level or activity of the transcription factor. Our results suggest that a subset of gene expression changes may be more predictive of ultimate phenotypes than the number of genes affected or the total fraction of variation in gene expression variation explained by causative variants, and that the downstream phenotype is buffered against variation in the gene expression network. PMID:24784239

  18. Integrative phenomics reveals insight into the structure of phenotypic diversity in budding yeast

    PubMed Central

    Skelly, Daniel A.; Merrihew, Gennifer E.; Riffle, Michael; Connelly, Caitlin F.; Kerr, Emily O.; Johansson, Marnie; Jaschob, Daniel; Graczyk, Beth; Shulman, Nicholas J.; Wakefield, Jon; Cooper, Sara J.; Fields, Stanley; Noble, William S.; Muller, Eric G.D.; Davis, Trisha N.; Dunham, Maitreya J.; MacCoss, Michael J.; Akey, Joshua M.

    2013-01-01

    To better understand the quantitative characteristics and structure of phenotypic diversity, we measured over 14,000 transcript, protein, metabolite, and morphological traits in 22 genetically diverse strains of Saccharomyces cerevisiae. More than 50% of all measured traits varied significantly across strains [false discovery rate (FDR) = 5%]. The structure of phenotypic correlations is complex, with 85% of all traits significantly correlated with at least one other phenotype (median = 6, maximum = 328). We show how high-dimensional molecular phenomics data sets can be leveraged to accurately predict phenotypic variation between strains, often with greater precision than afforded by DNA sequence information alone. These results provide new insights into the spectrum and structure of phenotypic diversity and the characteristics influencing the ability to accurately predict phenotypes. PMID:23720455

  19. Quantitation of fixative-induced morphologic and antigenic variation in mouse and human breast cancers

    PubMed Central

    Cardiff, Robert D; Hubbard, Neil E; Engelberg, Jesse A; Munn, Robert J; Miller, Claramae H; Walls, Judith E; Chen, Jane Q; Velásquez-García, Héctor A; Galvez, Jose J; Bell, Katie J; Beckett, Laurel A; Li, Yue-Ju; Borowsky, Alexander D

    2013-01-01

    Quantitative Image Analysis (QIA) of digitized whole slide images for morphometric parameters and immunohistochemistry of breast cancer antigens was used to evaluate the technical reproducibility, biological variability, and intratumoral heterogeneity in three transplantable mouse mammary tumor models of human breast cancer. The relative preservation of structure and immunogenicity of the three mouse models and three human breast cancers was also compared when fixed with representatives of four distinct classes of fixatives. The three mouse mammary tumor cell models were an ER + /PR + model (SSM2), a Her2 + model (NDL), and a triple negative model (MET1). The four breast cancer antigens were ER, PR, Her2, and Ki67. The fixatives included examples of (1) strong cross-linkers, (2) weak cross-linkers, (3) coagulants, and (4) combination fixatives. Each parameter was quantitatively analyzed using modified Aperio Technologies ImageScope algorithms. Careful pre-analytical adjustments to the algorithms were required to provide accurate results. The QIA permitted rigorous statistical analysis of results and grading by rank order. The analyses suggested excellent technical reproducibility and confirmed biological heterogeneity within each tumor. The strong cross-linker fixatives, such as formalin, consistently ranked higher than weak cross-linker, coagulant and combination fixatives in both the morphometric and immunohistochemical parameters. PMID:23399853

  20. Quantitation of fixative-induced morphologic and antigenic variation in mouse and human breast cancers.

    PubMed

    Cardiff, Robert D; Hubbard, Neil E; Engelberg, Jesse A; Munn, Robert J; Miller, Claramae H; Walls, Judith E; Chen, Jane Q; Velásquez-García, Héctor A; Galvez, Jose J; Bell, Katie J; Beckett, Laurel A; Li, Yue-Ju; Borowsky, Alexander D

    2013-04-01

    Quantitative Image Analysis (QIA) of digitized whole slide images for morphometric parameters and immunohistochemistry of breast cancer antigens was used to evaluate the technical reproducibility, biological variability, and intratumoral heterogeneity in three transplantable mouse mammary tumor models of human breast cancer. The relative preservation of structure and immunogenicity of the three mouse models and three human breast cancers was also compared when fixed with representatives of four distinct classes of fixatives. The three mouse mammary tumor cell models were an ER+/PR+ model (SSM2), a Her2+ model (NDL), and a triple negative model (MET1). The four breast cancer antigens were ER, PR, Her2, and Ki67. The fixatives included examples of (1) strong cross-linkers, (2) weak cross-linkers, (3) coagulants, and (4) combination fixatives. Each parameter was quantitatively analyzed using modified Aperio Technologies ImageScope algorithms. Careful pre-analytical adjustments to the algorithms were required to provide accurate results. The QIA permitted rigorous statistical analysis of results and grading by rank order. The analyses suggested excellent technical reproducibility and confirmed biological heterogeneity within each tumor. The strong cross-linker fixatives, such as formalin, consistently ranked higher than weak cross-linker, coagulant and combination fixatives in both the morphometric and immunohistochemical parameters. PMID:23399853

  1. Phenotypic profiling of DPYD variations relevant to 5-fluorouracil sensitivity using real-time cellular analysis and in vitro measurement of enzyme activity.

    PubMed

    Offer, Steven M; Wegner, Natalie J; Fossum, Croix; Wang, Kangsheng; Diasio, Robert B

    2013-03-15

    In the 45 years since its development, the pyrimidine analog 5-fluorouracil (5-FU) has become an integral component of many cancer treatments, most notably for the management of colorectal cancer. An appreciable fraction of patients who receive 5-FU suffer severe adverse toxicities, which in extreme cases may result in death. Dihydropyrimidine dehydrogenase (DPD, encoded by DPYD) rapidly degrades 85% of administered 5-FU, and as such, limits the amount of drug available for conversion into active metabolites. Clinical studies have suggested that genetic variations in DPYD increase the risk for 5-FU toxicity, however, there is not a clear consensus about which variations are relevant predictors. In the present study, DPYD variants were expressed in mammalian cells, and the enzymatic activity of expressed protein was determined relative to wild-type (WT). Relative sensitivity to 5-FU for cells expressing DPYD variations was also measured. The DPYD*2A variant (exon 14 deletion caused by IVS14+1G>A) was confirmed to be catalytically inactive. Compared with WT, two variants, S534N and C29R, showed significantly higher enzymatic activity. Cells expressing S534N were more resistant to 5-FU-mediated toxicity compared with cells expressing WT DPYD. These findings support the hypothesis that selected DPYD alleles are protective against severe 5-FU toxicity, and, as a consequence, may decrease the effectiveness of 5-FU an antitumor drug in carriers. In addition, this study shows a method that may be useful for phenotyping other genetic variations in pharmacologically relevant pathways. PMID:23328581

  2. Phenotypic profiling of DPYD variations relevant to 5-fluorouracil sensitivity using real-time cellular analysis and in vitro measurement of enzyme activity

    PubMed Central

    Offer, Steven M.; Wegner, Natalie J.; Fossum, Croix; Wang, Kangsheng; Diasio, Robert B.

    2013-01-01

    In the 45 years since its development, the pyrimidine analog 5-fluorouracil (5-FU) has become an integral component of many cancer treatments, most notably for the management of colorectal cancer. An appreciable fraction of patients who receive 5-FU suffer severe adverse toxicities, which in extreme cases may result in death. Dihydropyrimidine dehydrogenase (DPD, encoded by DPYD) rapidly degrades 85% of administered 5-FU, and as such, limits the amount of drug available for conversion into active metabolites. Clinical studies have suggested that genetic variations in DPYD increase the risk for 5-FU toxicity, however there is not a clear consensus as to which variations are relevant predictors. In the present study, DPYD variants were expressed in mammalian cells, and the enzymatic activity of expressed protein was determined relative to wild type. Relative sensitivity to 5-FU for cells expressing DPYD variations was also measured. The DPYD*2A variant (exon 14 deletion caused by IVS14+1G>A) was confirmed to be catalytically inactive. Compared to wild type, two variants, S534N and C29R, showed significantly higher enzymatic activity. Cells expressing S534N were more resistant to 5-FU mediated toxicity compared to cells expressing wild type DPYD. These findings support the hypothesis that selected DPYD alleles are protective against severe 5-FU toxicity, and, as a consequence, may decrease the effectiveness of 5-FU an anti tumor drug in carriers. Additionally, this study demonstrates a method that may be useful for phenotyping other genetic variations in pharmacologically relevant pathways. PMID:23328581

  3. Variation in TREK1 gene linked to depression-resistant phenotype is associated with potentiated neural responses to rewards in humans

    PubMed Central

    Dillon, Daniel G.; Bogdan, Ryan; Fagerness, Jesen; Holmes, Avram J.; Perlis, Roy H.; Pizzagalli, Diego A.

    2010-01-01

    The TREK1 gene has been linked to a depression-resistant phenotype in rodents and antidepressant response in humans, but the neural mechanisms underlying these links are unclear. Because TREK1 is expressed in reward-related basal ganglia regions, it has been hypothesized that TREK1 genetic variation may be associated with anhedonic symptoms of depression. To investigate whether TREK1 genetic variation influences reward processing, we genotyped healthy individuals (n = 31) who completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Three genotypes previously linked to positive antidepressant response were associated with potentiated basal ganglia activity to gains, but did not influence responses to penalties or no change feedback. TREK1 genetic variations did not affect basal ganglia volume, and fMRI group differences were confirmed when accounting for self-report measures of anhedonia. In addition, the total number of “protective” TREK1 alleles was associated with stronger responses to gains in several other reward-related regions, including the dorsal anterior cingulate cortex, orbitofrontal cortex, and mesial prefrontal cortex. In control analyses, associations between basal ganglia responses to gains and functional polymorphisms in the dopamine transporter (DAT1) and catechol-O-methyltransferase (COMT) genes were also explored. Results revealed that TREK1 and DAT/COMT genotypes were independently related to basal ganglia responses to gains. These findings indicate that TREK1 genotypes are associated with individual differences in reward-related brain activity. Future studies in depressed samples should evaluate whether variation in neural responses to rewards may contribute to the association between TREK1 and antidepressant response in humans. PMID:19621370

  4. Decomposing variation in population growth into contributions from environment and phenotypes in an age-structured population

    PubMed Central

    Pelletier, Fanie; Moyes, Kelly; Clutton-Brock, Tim H.; Coulson, Tim

    2012-01-01

    Evaluating the relative importance of ecological drivers responsible for natural population fluctuations in size is challenging. Longitudinal studies where most individuals are monitored from birth to death and where environmental conditions are known provide a valuable resource to characterize complex ecological interactions. We used a recently developed approach to decompose the observed fluctuation in population growth of the red deer population on the Isle of Rum into contributions from climate, density and their interaction and to quantify their relative importance. We also quantified the contribution of individual covariates, including phenotypic and life-history traits, to population growth. Fluctuations in composition in age and sex classes ((st)age structure) of the population contributed substantially to the population dynamics. Density, climate, birth weight and reproductive status contributed less and approximately equally to the population growth. Our results support the contention that fluctuations in the population's (st)age structure have important consequences for population dynamics and underline the importance of including information on population composition to understand the effect of human-driven changes on population performance of long-lived species. PMID:21715404

  5. An experimental method for evaluating the contribution of deleterious mutations to quantitative trait variation

    E-print Network

    Kelly, John K.

    1999-06-01

    is often formally defined as a ratio.) Under the model outlined above, the directional dominance associated with a single locus is fi2pqd (Cockerham & Weir, 1984). The overall value for B is the sum of this quantity across all quantitative trait loci. Using...?809), we find the approximate bias and sampling variance of the ratio of V a *toC ad *: E 9 C ad * V a * fi C ad V a : E 1 V a # 9 s aa 0 C ad V a 1 fis ad : (3) and V 9 C ad * V a * : E 1 V a # 9 s aa 0 C ad V a 1 # ?s dd fi2s ad 0 C ad V a 1: , (4) where...

  6. Morphometrics and the role of the phenotype in studies of the evolution of developmental mechanisms

    E-print Network

    Klingenberg, Christian Peter

    Morphometrics and the role of the phenotype in studies of the evolution of developmental mechanisms. Morphometrics permits the rigorous quantitative analysis of variation in organismal size and shape, and is increasingly being used in developmental contexts. The new methods of morphometrics combine a geometric concept

  7. Diversification of andromonoecy in Solanum section Lasiocarpa (Solanaceae): the roles of phenotypic plasticity and architecture

    Microsoft Academic Search

    JILL S. MILLER; PAMELA K. DIGGLE

    2003-01-01

    Quantitative analyses of sexual expression show extensive interspecific variation in the strength of andromonoecy (proportions of hermaphroditic and staminate flowers) among Solanum species in the monophyletic section Lasiocarpa. The roles of phenotypic plasticity and inter- and intra-inflorescence architecture in the diversification of andromonoecy within this small clade were analyzed. Four species that represent a range of expression of andromonoecy were

  8. Effects of Bos taurus autosome 9-located quantitative trait loci haplotypes on the disease phenotypes of dairy cows with experimentally induced Escherichia coli mastitis.

    PubMed

    Khatun, M; Sørensen, P; Jørgensen, H B H; Sahana, G; Sørensen, L P; Lund, M S; Ingvartsen, K L; Buitenhuis, A J; Vilkki, J; Bjerring, M; Thomasen, J R; Røntved, C M

    2013-03-01

    Several quantitative trait loci (QTL) affecting mastitis incidence and mastitis-related traits such as somatic cell score exist in dairy cows. Previously, QTL haplotypes associated with susceptibility to Escherichia coli mastitis in Nordic Holstein-Friesian (HF) cows were identified on Bos taurus autosome 9. In the present study, we induced experimental E. coli mastitis in Danish HF cows to investigate the effect of 2 E. coli mastitis-associated QTL haplotypes on the cows' disease phenotypes and recovery in early lactation. Thirty-two cows were divided in 2 groups bearing haplotypes with either low (HL) or high (HH) susceptibility to E. coli. In addition, biopsies (liver and udder) were collected from half of the cows (n=16), resulting in a 2 × 2 factorial design, with haplotype being one factor (HL vs. HH) and biopsy being the other factor (biopsies vs. no biopsies). Each cow was inoculated with a low E. coli dose (20 to 40 cfu) in one front quarter at time 0 h. Liver biopsies were collected at -144, 12, 24, and 192 h; udder biopsies were collected at 24h and 192 h post-E. coli inoculation. The clinical parameters: feed intake, milk yield, body temperature, heart rate, respiration rate, rumen motility; and the paraclinical parameters: bacterial counts, somatic cell count (SCC), and milk amyloid A levels in milk; and white blood cell count, polymorphonuclear neutrophilic leukocyte (PMNL) count, and serum amyloid A levels in blood were recorded at different time points post-E. coli inoculation. Escherichia coli inoculation changed the clinical and paraclinical parameters in all cows except one that was not infected. Clinically, the HH group tended to have higher body temperature and heart rate than the HL group did. Paraclinically, the HL group had faster PMNL recruitment and SCC recovery than the HH group did. However, we also found interactions between the effects of haplotype and biopsy for body temperature, heart rate, and PMNL. In conclusion, when challenged with E. coli mastitis, HF cows with the specific Bos taurus autosome 9-located QTL haplotypes were associated with differences in leukocyte kinetics, with low-susceptibility cows having faster blood PMNL recruitment and SCC recovery and a tendency for a milder clinical response than the high-susceptibility cows did. PMID:23357017

  9. Are we Genomic Mosaics? Variations of the Genome of Somatic Cells can Contribute to Diversify our Phenotypes

    PubMed Central

    Astolfi, P.A.; Salamini, F.; Sgaramella, V.

    2010-01-01

    Theoretical and experimental evidences support the hypothesis that the genomes and the epigenomes may be different in the somatic cells of complex organisms. In the genome, the differences range from single base substitutions to chromosome number; in the epigenome, they entail multiple postsynthetic modifications of the chromatin. Somatic genome variations (SGV) may accumulate during development in response both to genetic programs, which may differ from tissue to tissue, and to environmental stimuli, which are often undetected and generally irreproducible. SGV may jeopardize physiological cellular functions, but also create novel coding and regulatory sequences, to be exposed to intraorganismal Darwinian selection. Genomes acknowledged as comparatively poor in genes, such as humans’, could thus increase their pristine informational endowment. A better understanding of SGV will contribute to basic issues such as the “nature vs nurture” dualism and the inheritance of acquired characters. On the applied side, they may explain the low yield of cloning via somatic cell nuclear transfer, provide clues to some of the problems associated with transdifferentiation, and interfere with individual DNA analysis. SGV may be unique in the different cells types and in the different developmental stages, and thus explain the several hundred gaps persisting in the human genomes “completed” so far. They may compound the variations associated to our epigenomes and make of each of us an “(epi)genomic” mosaic. An ensuing paradigm is the possibility that a single genome (the ephemeral one assembled at fertilization) has the capacity to generate several different brains in response to different environments. PMID:21358981

  10. A comparison of isozyme and quantitative genetic variation in Pinus contorta ssp. latifolia by F{sub ST}

    SciTech Connect

    Yang, Rong-Cai; Yeh, F.C. [Univ. of Alberta, Edmonton (Canada); Yanchuk, A.D. [British Columbia Ministry of Forests (Canada)

    1996-03-01

    We employed F-statistics to analyze quantitative and isozyme variation among five populations of Pinus contorta ssp. latifolia, a wind-pollinated outcrossing conifer with wide and continuous distribution in west North America. Estimates of population differentiation (F{sub ST}) for six quantitative traits were compared with the overall estimate of the differentiation (F*{sub ST}) from 19 isozymes that tested neutral to examine whether similar evolutionary processes were involved in morphological and isozyme differentiation. While the F{sub ST} estimates for specific gravity, stem diameter, stem height and branch length were significantly greater than the F*{sub ST} estimate, as judged from the 95% confidence intervals by bootstrapping, the F{sub ST} estimates for branch angle and branch diameter were indistinguishable from the F*{sub ST} estimate. Differentiation in stem height and stem diameter might reflect the inherent adaptation of the populations for rapid growth to escape suppression by neighboring plants during establishment and to regional differences in photoperiod, precipitation and temperature. In contrast, divergences in wood specific gravity and branch length might be correlated responses to population differentiation in stem growth. Possible bias in the estimation of F{sub ST} due to Hardy-Weinberg disequilibrium (F{sub IS} {ne} 0), linkage disequilibrium, maternal effects and nonadditive genetic effects was discussed with special reference to P. contorta ssp. latifolia. 48 refs., 1 fig., 3 tabs.

  11. Comparing label-free quantitative peptidomics approaches to characterize diurnal variation of peptides in the rat suprachiasmatic nucleus.

    PubMed

    Southey, Bruce R; Lee, Ji Eun; Zamdborg, Leonid; Atkins, Norman; Mitchell, Jennifer W; Li, Mingxi; Gillette, Martha U; Kelleher, Neil L; Sweedler, Jonathan V

    2014-01-01

    Mammalian circadian rhythm is maintained by the suprachiasmatic nucleus (SCN) via an intricate set of neuropeptides and other signaling molecules. In this work, peptidomic analyses from two times of day were examined to characterize variation in SCN peptides using three different label-free quantitation approaches: spectral count, spectra index and SIEVE. Of the 448 identified peptides, 207 peptides were analyzed by two label-free methods, spectral count and spectral index. There were 24 peptides with significant (adjusted p-value < 0.01) differential peptide abundances between daytime and nighttime, including multiple peptides derived from secretogranin II, cocaine and amphetamine regulated transcript, and proprotein convertase subtilisin/kexin type 1 inhibitor. Interestingly, more peptides were analyzable and had significantly different abundances between the two time points using the spectral count and spectral index methods than with a prior analysis using the SIEVE method with the same data. The results of this study reveal the importance of using the appropriate data analysis approaches for label-free relative quantitation of peptides. The detection of significant changes in so rich a set of neuropeptides reflects the dynamic nature of the SCN and the number of influences such as feeding behavior on circadian rhythm. Using spectral count and spectral index, peptide level changes are correlated to time of day, suggesting their key role in circadian function. PMID:24313826

  12. Genetic variation and quantitative trait loci associated with developmental stability and the environmental correlation between traits in maize.

    PubMed

    Ordas, Bernardo; Malvar, Rosa A; Hill, William G

    2008-10-01

    There is limited experimental information about the genetic basis of micro-environmental variance (V(E)) (developmental stability) and environmental correlations. This study, by using a population of maize recombinant inbred lines (RIL) and simple sequence repeat (SSR) polymorphic markers, aims at the following: firstly, to quantify the genetic component of the V(E) or developmental stability for four traits in maize and the environmental correlation between these traits, and secondly, to identify quantitative trait loci (QTLs) that influence these quantities. We found that, when estimating variances and correlations and testing their homogeneity, estimates and tests are needed that are not highly dependent on normality assumptions. There was significant variation among the RILs in V(E) and in the environmental correlation for some of the traits, implying genetic heterogeneity in the V(E) and environmental correlations. The genetic coefficient of variation of the environmental variance (GCV(V(E))) was estimated to be 20%, which is lower than estimates obtained for other species. A few genomic regions involved in the stability of one trait or two traits were detected, and these did not have an important influence on the mean of the trait. One region that could be associated with the environmental correlations between traits was also detected. PMID:19061529

  13. Quantitative Monitoring for Enhanced Geothermal Systems Using Double-Difference Waveform Inversion with Spatially-Variant Total-Variation Regularization

    SciTech Connect

    Lin, Youzuo [Los Alamos National Laboratory; Huang, Lianjie [Los Alamos National Laboratory; Zhang, Zhigang [Los Alamos National Laboratory

    2011-01-01

    Double-difference waveform inversion is a promising tool for quantitative monitoring for enhanced geothermal systems (EGS). The method uses time-lapse seismic data to jointly inverts for reservoir changes. Due to the ill-posedness of waveform inversion, it is a great challenge to obtain reservoir changes accurately and efficiently, particularly when using timelapse seismic reflection data. To improve reconstruction, we develop a spatially-variant total-variation regularization scheme into double-difference waveform inversion to improve the inversion accuracy and robustness. The new regularization scheme employs different regularization parameters in different regions of the model to obtain an optimal regularization in each area. We compare the results obtained using a spatially-variant parameter with those obtained using a constant regularization parameter. Utilizing a spatially-variant regularization scheme, the target monitoring regions are well reconstructed and the image noise is significantly reduced outside the monitoring regions. Our numerical examples demonstrate that the spatially-variant total-variation regularization scheme provides the flexibility to regularize local regions based on the a priori spatial information without increasing computational costs and the computer memory requirement.

  14. Leaf physiological aspects of nitrogen-use efficiency in Brassica campestris L.: quantitative genetic variation across nutrient treatments.

    PubMed

    Evans, A S

    1991-01-01

    Quantitative genetic parameters for leaf physiological and whole-plant aspects of nitrogen-use efficiency in Brassica camprestris L. were estimated in three nutrient treatments in the greenhouse. Narrow-sense heritabilities and genetic correlations varied across treatments for some traits. Sire effects were significant for leaf nitrogen content in near-optimal and super-optimal, but not in suboptimal nutrient treatments. Additive genetic variation for two estimates of leaf physiological nitrogen-use efficiency (nitrogen-based photosynthetic capacity and leaf carbon: nitrogen ratio) was significant only in the suboptimal nutrient treatment. Area-based photosynthetic capacity, on the other hand, exhibited no heritable variation in any nutrient treatment. Heritability estimates of aboveground biomass and flower production were greatest in sub- and super-optimal treatments, respectively. Negative genetic correlations between leaf nitrogen content and both estimates of leaf nitrogen-use efficiency were evident in the super-optimal treatment. Aboveground biomass and leaf nitrogen-use efficiency were positively correlated in the suboptimal treatment, suggesting that growth differences were due in part to the efficiency with which nitrogen was utilized in physiological processes. Although implications for breeding may differ for different sources of germ plasm or different measures of performance or yield, selection for improved whole-plant performance through increased nitrogen-use efficiency should proceed best in suboptimal nutrient treatments. PMID:24221160

  15. A semi-quantitative approach to variation of the azygos vein course.

    PubMed

    Bales, G

    2014-10-01

    The azygos vein (AV) is typically described (illustrated) as ascending vertically on the right of thoracic vertebrae. Most thoracic vein studies have focused on tributary patterns, but some have noted more leftward AV courses. This study statistically documents variation in AV course independent of tributary patterns. A more statistical approach to the probable position of AV at different vertical levels may aid clinicians in locating and assessing it in clinical contexts. The AV course was exposed in 84 cadavers by removing overlying viscera between the aortic hiatus and tracheal bifurcation. Subjectively, non-pathological specimens were digitally photographed in anterior view. For each photo, a scaled grid was used to mark the horizontal position of the AV center at each of five vertical levels. The summated numerical distributions showed the following: ?5% of the AVs ascended on the right side (classical) position, ?30% did not cross the midline, ?70% included part or all of their course left of the midline, and ?14% reached the extreme left side. Based on this data, the modal AV course (1) begins at, or to the right of, the midline, (2) deviates leftward, (3) crosses the midline below mid-level, (4) reaches a leftward maximum at about 3/5 of its course, (5) then deviates rightward (often only reaching the midline at the uppermost level). In several noticeable cases, the leftward maximum was associated with large connections to left-side veins, suggesting a possible tension mechanism exerting traction on the AV over time. PMID:24442867

  16. Quantitative estimation of Holocene surface salinity variation in the Black Sea using dinoflagellate cyst process length

    NASA Astrophysics Data System (ADS)

    Mertens, Kenneth Neil; Bradley, Lee R.; Takano, Yoshihito; Mudie, Petra J.; Marret, Fabienne; Aksu, Ali E.; Hiscott, Richard N.; Verleye, Thomas J.; Mousing, Erik A.; Smyrnova, Ludmila L.; Bagheri, Siamak; Mansor, Mashhor; Pospelova, Vera; Matsuoka, Kazumi

    2012-04-01

    Reconstruction of salinity in the Holocene Black Sea has been an ongoing debate over the past four decades. Here we calibrate summer surface water salinity in the Black Sea, Sea of Azov and Caspian Sea with the process length of the dinoflagellate cyst Lingulodinium machaerophorum. We then apply this calibration to make a regional reconstruction of paleosalinity in the Black Sea, calculated by averaging out process length variation observed at four core sites from the Black Sea with high sedimentation rates and dated by multiple mollusk shell ages. Results show a very gradual change of salinity from ˜14 ± 0.91 psu around 9.9 cal ka BP to a minimum ˜12.3 ± 0.91 psu around 8.5 cal ka BP, reaching current salinities of ˜17.1 ± 0.91 psu around 4.1 cal ka BP. The resolution of our sampling is about 250 years, and it fails to reveal a catastrophic salinization event at ˜9.14 cal ka BP advocated by other researchers. The dinoflagellate cyst salinity-proxy does not record large Holocene salinity fluctuations, and after early Holocene freshening, it shows correspondence to the regional sea-level curve of Brückner et al. (2010) derived from Balabanov (2007).

  17. Variation in urinary excretion of FDG, yet another uncertainty in quantitative PET

    PubMed Central

    Bach-Gansmo, Tore; Dybvik, JA; Adamsen, TC; Naum, A

    2012-01-01

    Background The standardized uptake value (SUV) is the most common estimate of metabolic activity used in clinical positron emission tomography (PET). Several biological and technological factors influence the accurate SUV calculation. Purpose To assess another potential source of variability of the SUV, the variations in urinary excretion of fluorodeoxyglucose (FDG). Material and Methods Twenty patients with various malignancies scheduled for PET/CT with 18F-FDG were included in the present study. The activity in urine voided immediately before image acquisition was measured and decay corrected. An estimation of FDG content in the urinary bladder was made during imaging, and the two components of urinary FDG were added. The urinary output of FDG, and the quantity of FDG divided by the time to measurements, was estimated. Results The excretion of FDG in urine was between 5.7% and 15.2% of injected dose (decay corrected), and from 0.06% to 0.3%/min after injection, a five-fold difference in clearance. Conclusion About 10% of injected dose is excreted in urine at 70 min post injection, but the urinary FDG excretion was found to be highly variable, yet another uncertainty affecting the SUV measurements. PMID:23986849

  18. Individual quality, survival variation and patterns of phenotypic selection on body condition and timing of nesting in birds

    USGS Publications Warehouse

    Blums, P.; Nichols, J.D.; Hines, J.E.; Lindberg, M.; Mednis, A.

    2005-01-01

    Questions about individual variation in 'quality' and fitness are of great interest to evolutionary and population ecologists. Such variation can be investigated using either a random effects approach or an approach that relies on identifying observable traits that are themselves correlated with fitness components. We used the latter approach with data from 1,925 individual females of three species of ducks (tufted duck, Aythya fuligula; common pochard, Aythya ferina; northern shoveler, Anas clypeata) sampled on their breeding grounds at Engure Marsh, Latvia, for over 15 years. Based on associations with reproductive output, we selected two traits, one morphological (relative body condition) and one behavioral (relative time of nesting), that can be used to characterize individual females over their lifetimes. We then asked whether these traits were related to annual survival probabilities of nesting females. We hypothesized quadratic, rather than monotonic, relationships based loosely on ideas about the likely action of stabilizing selection on these two traits. Parameters of these relationships were estimated directly using ultrastructural models embedded within capture-recapture-band-recovery models. Results provided evidence that both traits were related to survival in the hypothesized manner. For all three species, females that tended to nest earlier than the norm exhibited the highest survival rates, but very early nesters experienced reduced survival and late nesters showed even lower survival. For shovelers, females in average body condition showed the highest survival, with lower survival rates exhibited by both heavy and light birds. For common pochard and tufted duck, the highest survival rates were associated with birds of slightly above-average condition, with somewhat lower survival for very heavy birds and much lower survival for birds in relatively poor condition. Based on results from this study and previous work on reproduction, we conclude that nest initiation date and body condition covary with both reproductive and survival components of fitness. These associations lead to a positive covariance of these two fitness components within individuals and to the conclusion that these two traits are indeed correlates of individual quality.

  19. The genetic and molecular origin of natural variation for the fragrance trait in an elite Malaysian aromatic rice through quantitative trait loci mapping using SSR and gene-based markers.

    PubMed

    Golestan Hashemi, Farahnaz Sadat; Rafii, Mohd Y; Ismail, Mohd Razi; Mohamed, Mahmud Tengku Muda; Rahim, Harun A; Latif, Mohammad Abdul; Aslani, Farzad

    2015-01-25

    MRQ74, a popular aromatic Malaysian landrace, allows for charging considerably higher prices than non-aromatic landraces. Thus, breeding this profitable trait has become a priority for Malaysian rice breeding. Despite many studies on aroma genetics, ambiguities considering its genetic basis remain. It has been observed that identifying quantitative trait loci (QTLs) based on anchor markers, particularly candidate genes controlling a trait of interest, can increase the power of QTL detection. Hence, this study aimed to locate QTLs that influence natural variations in rice scent using microsatellites and candidate gene-based sequence polymorphisms. For this purpose, an F2 mapping population including 189 individual plants was developed by MRQ74 crosses with 'MR84', a non-scented Malaysian accession. Additionally, qualitative and quantitative approaches were applied to obtain a phenotype data framework. Consequently, we identified two QTLs on chromosomes 4 and 8. These QTLs explained from 3.2% to 39.3% of the total fragrance phenotypic variance. In addition, we could resolve linkage group 8 by adding six gene-based primers in the interval harboring the most robust QTL. Hence, we could locate a putative fgr allele in the QTL found on chromosome 8 in the interval RM223-SCU015RM (1.63cM). The identified QTLs represent an important step toward recognition of the rice flavor genetic control mechanism. In addition, this identification will likely accelerate the progress of the use of molecular markers for gene isolation, gene-based cloning, and marker-assisted selection breeding programs aimed at improving rice cultivars. PMID:25445269

  20. Cranial Ontogeny in Stegoceras validum (Dinosauria: Pachycephalosauria): A Quantitative Model of Pachycephalosaur Dome Growth and Variation

    PubMed Central

    Schott, Ryan K.; Evans, David C.; Goodwin, Mark B.; Horner, John R.; Brown, Caleb Marshall; Longrich, Nicholas R.

    2011-01-01

    Historically, studies of pachycephalosaurs have recognized plesiomorphically flat-headed taxa and apomorphically domed taxa. More recently, it has been suggested that the expression of the frontoparietal dome is ontogenetic and derived from a flat-headed juvenile morphology. However, strong evidence to support this hypothesis has been lacking. Here we test this hypothesis in a large, stratigraphically constrained sample of specimens assigned to Stegoceras validum, the best known pachycephalosaur, using multiple independent lines of evidence including conserved morphology of ornamentation, landmark-based allometric analyses of frontoparietal shape, and cranial bone histology. New specimens show that the diagnostic ornamentation of the parietosquamosal bar is conserved throughout the size range of the sample, which links flat-headed specimens to domed S. validum. High-resolution CT scans of three frontoparietals reveal that vascularity decreases with size and document a pattern that is consistent with previously proposed histological changes during growth. Furthermore, aspects of dome shape and size are strongly correlated and indicative of ontogenetic growth. These results are complementary and strongly support the hypothesis that the sample represents a growth series of a single taxon. Cranial dome growth is positively allometric, proceeds from a flat-headed to a domed state, and confirms the synonymy of Ornatotholus browni as a juvenile Stegoceras. This dataset serves as the first detailed model of growth and variation in a pachycephalosaur. Flat-headed juveniles possess three characters (externally open cranial sutures, tuberculate dorsal surface texture, and open supratemporal fenestrae) that are reduced or eliminated during ontogeny. These characters also occur in putative flat-headed taxa, suggesting that they may also represent juveniles of domed taxa. However, open cranial sutures and supratemporal fenestrae are plesiomorphic within Ornithischia, and thus should be expected in the adult stage of a primitive pachycephalosaur. Additional lines of evidence will be needed to resolve the taxonomic validity of flat-headed pachycephalosaur taxa. PMID:21738608

  1. Quantitative flavonoid variation accompanied by change of flower colors in Edgeworthia chrysantha, Pittosporum tobira and Wisteria floribunda.

    PubMed

    Ono, Megumi; Iwashina, Tsukasa

    2015-03-01

    The flavonoids in the flowers of Edgeworthia chrysantha, Pittosporum tobira and Wisteria floribunda were isolated and identified. Quercetin and kaempferol 3-O-glucosides and 3-O-rutinosides were found in E. chrysantha, and quercetin 3-O-rutinoside, 3-O-glucoside and 3-O-pentosylrhamnosylglucoside, kaempferol 3-O-robinobioside, 3-O-rutinoside, 3-O-glucoside and 3-O-pentosylrhamnosylglucoside, and isorhamnetin 3-O-rutinoside were isolated from P. tobira. Ten flavonoids, quercetin 3-O-sophoroside, 3-O-rutinoside, 3-O-glucoside, kaempferol 3-O-sophoroside and 3-O-glucoside, luteolin 5-O-glucoside, 7- O-glucoside and 7-O-hexoside, and apigenin 7-O-glucoside and 4'-O-hexoside were isolated from W floribunda. The major pigments of E. chrysantha were carotenoids. Their content decreased with the change in flower color to white from yellow via cream, and total flavonoid content also slightly decreased by ca. 0.8 in cream and ca. 0.9 fold in white flowers. In contrast with E. chrysantha, white flowers of P. tobira turn to cream and then yellow in which the major pigments are also carotenoids. In this species, both carotenoid and flavonoid contents are gradually increased from white to yellow flowers. Though the petal color of Wisteria floribunda is mauve, due to anthocyanin pigments, the yellow areas are due to carotenoids; these turn to white in the late flowering stage. However, their flavonoid contents were essentially the same among the yellow, cream and white spots of flags. Thus, it was shown by HPLC analysis of the flower flavonoids of E. chrysantha, P. tobira and W. floribunda, although the visible pigments such as carotenoids and anthocyanins are quantitatively varied, the quantitative variation in UV-absorbing substances, such as flavones and flavonols, differs with plant species. PMID:25924517

  2. Comparative sex pherome biosynthesis in Thaumetopoea pityocampa and T. processionea: a rationale for the phenotypic variation in the sex pherome within the genus Thaumetopoea.

    PubMed

    Villorbina, G; Rodríguez, S; Camps, F; Fabriàs, G

    2003-02-01

    The female sex pheromones of the Mediterranean processionary moths (Thaumetopoea sp.) are conjugated dienes or enynes of 16 carbon atoms with the unsaturations located at C11 and C13. To investigate the biochemical basis of this phenotypic variation, the biosynthetic pathway of T. processionea sex pheromone, a diene acetate, has been elucidated and compared to that reported for the enyne-producing species T. pityocampa. Mass labeling experiments showed that T. processionea sex pheromone is biosynthesized from palmitic acid, by subsequent (Z)-11 and (Z)-13 desaturations and final reduction and acetylation. The Pheromone Biosynthesis Activating Neuropeptide (PBAN) activates this biosynthetic pathway downstream of the dienoate intermediate. When either 11-hexadecynoic acid or (Z)-13-hexadecen-11-ynoic acid were administered to T. processionea, this species was able to produce the enyne sex pheromone of T. pityocampa upon PBAN stimulation. In contrast, T. pityocampa does not produce either 11-hexadecynyl acetate or (Z,Z)-11,13-hexadecadienyl acetate, despite having the corresponding precursors in the pheromone gland. However, both acetates are detected after administration of the corresponding alcohols. These overall results suggest that the absence of delta(11) acetylenase and the existence of an enynoate specific reductase in the diene and enyne-producing Thaumetopeae, respectively, account for the different sex pheromones produced by the two groups. PMID:12535674

  3. The Distribution and ‘In Vivo’ Phase Variation Status of Haemoglobin Receptors in Invasive Meningococcal Serogroup B Disease: Genotypic and Phenotypic Analysis

    PubMed Central

    Lucidarme, Jay; Findlow, Jamie; Chan, Hannah; Feavers, Ian M.; Gray, Stephen J.; Kaczmarski, Edward B.; Parkhill, Julian; Bai, Xilian; Borrow, Ray; Bayliss, Christopher D.

    2013-01-01

    Two haemoglobin-binding proteins, HmbR and HpuAB, contribute to iron acquisition by Neisseria meningitidis. These receptors are subject to high frequency, reversible switches in gene expression - phase variation (PV) - due to mutations in homopolymeric (poly-G) repeats present in the open reading frame. The distribution and PV state of these receptors was assessed for a representative collection of isolates from invasive meningococcal disease patients of England, Wales and Northern Ireland. Most of the major clonal complexes had only the HmbR receptor whilst the recently expanding ST-275-centred cluster of the ST-269 clonal complex had both receptors. At least one of the receptors was in an ‘ON’ configuration in 76.3% of the isolates, a finding that was largely consistent with phenotypic analyses. As PV status may change during isolation and culture of meningococci, a PCR-based protocol was utilised to confirm the expression status of the receptors within contemporaneously acquired clinical specimens (blood/cerebrospinal fluid) from the respective patients. The expression state was confirmed for all isolate/specimen pairs with <15 tract repeats indicating that the PV status of these receptors is stable during isolation. This study therefore establishes a protocol for determining in vivo PV status to aid in determining the contributions of phase variable genes to invasive meningococcal disease. Furthermore, the results of the study support a putative but non-essential role of the meningococcal haemoglobin receptors as virulence factors whilst further highlighting their vaccine candidacy. PMID:24098814

  4. Genetic divergence is not the same as phenotypic divergence.

    PubMed

    Kozak, Marcin; Bocianowski, Jan; Liersch, Alina; Tartanus, Ma?gorzata; Bartkowiak-Broda, Iwona; Piotto, Fernando A; Azevedo, Ricardo A

    2011-08-01

    Far too often, phenotypic divergence has been misinterpreted as genetic divergence, and based on phenotypic divergence, genetic divergence has been indicated. We have attempted to disprove this statement and call for the differentiation of phenotypic and genotypic variation. PMID:21841910

  5. A recombination hotspot delimits a wild-species quantitative trait locus for tomato sugar content to 484 bp within an invertase gene

    Microsoft Academic Search

    Eyal Fridman; Tzili Pleban; Dani Zamir

    2000-01-01

    In nature, genetic variation usually takes the form of a continuous phenotypic range rather than discrete classes. The genetic variation underlying quantitative traits results from the segregation of numerous interacting quantitative trait loci (QTLs), whose expression is modified by the environment. To uncover the molecular basis of this variation, we characterized a QTL (Brix9-2-5) derived from the green-fruited tomato species

  6. Quantitative estimation of density variation in high-speed flows through inversion of the measured wavefront distortion

    NASA Astrophysics Data System (ADS)

    Medhi, Biswajit; Hegde, Gopalkrishna Mahadeva; Reddy, Kalidevapura Polareddy Jagannath; Roy, Debasish; Vasu, Ram Mohan

    2014-12-01

    A simple method employing an optical probe is presented to measure density variations in a hypersonic flow obstructed by a test model in a typical shock tunnel. The probe has a plane light wave trans-illuminating the flow and casting a shadow of a random dot pattern. Local slopes of the distorted wavefront are obtained from shifts of the dots in the pattern. Local shifts in the dots are accurately measured by cross-correlating local shifted shadows with the corresponding unshifted originals. The measured slopes are suitably unwrapped by using a discrete cosine transform based phase unwrapping procedure and also through iterative procedures. The unwrapped phase information is used in an iterative scheme for a full quantitative recovery of density distribution in the shock around the model through refraction tomographic inversion. Hypersonic flow field parameters around a missile shaped body at a free-stream Mach number of 5.8 measured using this technique are compared with the numerically estimated values.

  7. Phenotypic integration between antipredator behavior and camouflage pattern in juvenile sticklebacks.

    PubMed

    Kim, Sin-Yeon; Velando, Alberto

    2015-03-01

    Predation is a strong selective force that promotes the evolution of antipredator behaviors and camouflage in prey animals. However, the independent evolution of single traits cannot explain how observed phenotypic variations of these traits are maintained within populations. We studied genetic and phenotypic correlations between antipredator behaviors (shoaling and risk-taking) and morphology traits (pigmentation and size) in juvenile three-spined sticklebacks by using pedigree-based quantitative genetic analysis to test phenotypic integration (or complex phenotype) as an evolutionary response to predation risk. Individuals with strongly melanized (i.e., camouflaged) phenotype and genotype were less sociable to conspecifics, but bolder during foraging under predation risk. Individuals with faster growing phenotype and genotype were bolder, and those with lager eyes were more fearful. These phenotypic integrations were not confounded with correlated plastic responses to predation risk because the phenotypes were measured in naïve fish born in the laboratory, but originated from a natural population with predation pressure. Consistent selection for particular combinations of traits under predation pressure or pleiotropic genes might influence the maintenance of the genetic (co)variations and polymorphism in melanin color, growth trajectory, and behavior patterns. PMID:25572122

  8. Variation, selection and evolution of function-valued traits

    Microsoft Academic Search

    Joel G. Kingsolver; Richard Gomulkiewicz; Patrick A. Carter

    2001-01-01

    We describe an emerging framework for understanding variation, selection and evolution of phenotypic traits that are mathematical functions. We use one specific empirical example – thermal performance curves (TPCs) for growth rates of caterpillars – to demonstrate how models for function-valued traits are natural extensions of more familiar, multivariate models for correlated, quantitative traits. We emphasize three main points. First,

  9. Rapid evolution of quantitative traits: theoretical perspectives

    PubMed Central

    Kopp, Michael; Matuszewski, Sebastian

    2014-01-01

    An increasing number of studies demonstrate phenotypic and genetic changes in natural populations that are subject to climate change, and there is hope that some of these changes will contribute to avoiding species extinctions (‘evolutionary rescue’). Here, we review theoretical models of rapid evolution in quantitative traits that can shed light on the potential for adaptation to a changing climate. Our focus is on quantitative-genetic models with selection for a moving phenotypic optimum. We point out that there is no one-to-one relationship between the rate of adaptation and population survival, because the former depends on relative fitness and the latter on absolute fitness. Nevertheless, previous estimates that sustainable rates of genetically based change usually do not exceed 0.1 haldanes (i.e., phenotypic standard deviations per generation) are probably correct. Survival can be greatly facilitated by phenotypic plasticity, and heritable variation in plasticity can further speed up genetic evolution. Multivariate selection and genetic correlations are frequently assumed to constrain adaptation, but this is not necessarily the case and depends on the geometric relationship between the fitness landscape and the structure of genetic variation. Similar conclusions hold for adaptation to shifting spatial gradients. Recent models of adaptation in multispecies communities indicate that the potential for rapid evolution is strongly influenced by interspecific competition. PMID:24454555

  10. Biolog phenotype microarrays.

    PubMed

    Shea, April; Wolcott, Mark; Daefler, Simon; Rozak, David A

    2012-01-01

    Phenotype microarrays nicely complement traditional genomic, transcriptomic, and proteomic analysis by offering opportunities for researchers to ground microbial systems analysis and modeling in a broad yet quantitative assessment of the organism's physiological response to different metabolites and environments. Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally defined nutrients to measure the impact of hundreds of carbon, nitrogen, phosphorous, and sulfur sources on redox reactions that result from compound-induced effects on the electron transport chain. Over the years, we have used Biolog's reproducible and highly sensitive assays to distinguish closely related bacterial isolates, to understand their metabolic differences, and to model their metabolic behavior using flux balance analysis. This chapter describes Biolog phenotype microarray system components, reagents, and methods, particularly as they apply to bacterial identification, characterization, and metabolic analysis. PMID:22639219

  11. Phenotype-genotype correlations of facial width and height proportions in patients with Class II malocclusion

    PubMed Central

    Uribe, L.M. Moreno; Ray, A.; Blanchette, D. R.; Dawson, D.V.; Southard, T.E.

    2015-01-01

    Objectives To characterize soft tissue facial height and width variation in Class II malocclusion and test for correlations with genes HMGA2, AJUBA and ADK. Setting and Sample Population Nine facial proportions were estimated from 2D frontal repose photographs of 330 Caucasian adults with Class II malocclusion. Material & Methods After adjustments for age and gender, the facial proportions were submitted to a principal component analyses (PCA). The most meaningful phenotypic variations were correlated with SNPS rs7924176 (ADK), rs17101923 (HMGA2), and rs997154 (AJUBA) genotyped in 106 individuals. Results PCA resulted in 4 principal components (PCs) which explained 75% of total variation. PC1 captured variation in the intercanthus distance and explained 28% of total variation. PC2 explained 21% of the variations in facial taper and facial index. PC3 explained 14% and reflected variations in the vertical dimension of the lower face. PC4 explained 12% and captured variations in distance between the eyes, width of the commissures, and the length of the superior aspect of the lower face height, corresponding to the vertical dimension of the philtrum of the upper lip. A suggestive association (p<0.05) was observed between PC4 and rs997154 corroborating the role of AJUBA in variation of facial dimensions. Conclusion 2D frontal photographs can be used to derive quantitative measures of soft tissue phenotypes that are of clinical relevance. The methods described are suitable for discovery and replication of associations between genotypes and malocclusion phenotypes. PMID:25865538

  12. Behavioral idiosyncrasy reveals genetic control of phenotypic variability

    PubMed Central

    Ayroles, Julien F.; Buchanan, Sean M.; O’Leary, Chelsea; Skutt-Kakaria, Kyobi; Grenier, Jennifer K.; Clark, Andrew G.; Hartl, Daniel L.; de Bivort, Benjamin L.

    2015-01-01

    Quantitative genetics has primarily focused on describing genetic effects on trait means and largely ignored the effect of alternative alleles on trait variability, potentially missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study the genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used Drosophila inbred lines and measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes, focusing on variability in locomotor handedness, an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals, whereas lines with low variability behaved as although they tossed a coin at each left/right turn decision. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicates a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. Our study reveals the constellation of phenotypes that can arise from a single genotype and shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variabililty. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype. PMID:25953335

  13. A Qualitative and Quantitative Assay for Cells Lacking Postconfluence Inhibition of Cell Division: Characterization of This Phenotype in Carcinogen-treated Syrian Hamster Embryo Cells in Culture1

    Microsoft Academic Search

    Shuji Nakano; Sarah A. Bruce; Hiroaki Ueo; Paul O. P. Ts

    We have developed a qualitative and quantitative assay system for detecting cells lacking postconfluence inhibition of cell division (contact insensitivity, CS~) in golden Syrian ham ster embryo cells in culture by measuring the number of cells able to form colonies on a lethally irradiated, confluent mono- layer of a contact-sensitive established cell line. A subpopula- tion in normal low-passage cultures

  14. Quantitative Autism Traits in First Degree Relatives: Evidence for the Broader Autism Phenotype in Fathers, but Not in Mothers and Siblings

    ERIC Educational Resources Information Center

    De la Marche, Wouter; Noens, Ilse; Luts, Jan; Scholte, Evert; Van Huffel, Sabine; Steyaert, Jean

    2012-01-01

    Autism spectrum disorder (ASD) symptoms are present in unaffected relatives and individuals from the general population. Results are inconclusive, however, on whether unaffected relatives have higher levels of quantitative autism traits (QAT) or not. This might be due to differences in research populations, because behavioral data and molecular…

  15. Invariance and Meaningfulness in Phenotype spaces

    Microsoft Academic Search

    Simon M. Huttegger; Philipp Mitteroecker

    Mathematical spaces are widely used in the sciences for representing quantitative and qualitative relations between objects\\u000a or individuals. Phenotype spaces—spaces whose elements represent phenotypes—are frequently applied in morphometrics, evolutionary\\u000a quantitative genetics, and systematics. In many applications, several quantitative measurements are taken as the orthogonal\\u000a axes of a Euclidean vector space. We show that incommensurable units, geometric dependencies between measurements, and

  16. Identifying the loci that influence quantitative trait variation in oats: Lessons from human population-based GWAS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In recent years, the resources have become available to enable genome-wide genotype-phenotype association analyses in cereal crops using thousands of genetic markers measured on hundreds of lines. One open question is whether these resources are sufficient to identify the loci influencing quantitati...

  17. Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice

    Microsoft Academic Search

    Binnaz Yalcin; Saffron A G Willis-Owen; Jan Fullerton; Anjela Meesaq; Robert M Deacon; J Nicholas P Rawlins; Richard R Copley; Andrew P Morris; Jonathan Flint; Richard Mott

    2004-01-01

    Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing

  18. Topological Phenotypes in Complex Leaf Venation Networks

    NASA Astrophysics Data System (ADS)

    Ronellenfitsch, Henrik; Lasser, Jana; Daly, Douglas; Katifori, Eleni

    2015-03-01

    The leaves of vascular plants contain highly complex venation networks consisting of recursively nested, hierarchically organized loops. We analyze the topology of the venation of leaves from ca. 200 species belonging to ca. 10 families, defining topological metrics that quantify the hierarchical nestedness of the network cycles. We find that most of the venation variability can be described by a two dimensional phenotypic space, where one dimension consists of a linear combination of geometrical metrics and the other dimension of topological, previously uncharacterized metrics. We show how this new topological dimension in the phenotypic space significantly improves identification of leaves from fragments, by calculating a ``leaf fingerprint'' from the topology and geometry of the higher order veins. Further, we present a simple model suggesting that the topological phenotypic traits can be explained by noise effects and variations in the timing of higher order vein developmental events. This work opens the path to (a) new quantitative identification techniques for leaves which go beyond simple geometric traits such as vein density and (b) topological quantification of other planar or almost planar networks such as arterial vaculature in the neocortex and lung tissue.

  19. Epistasis and Quantitative Traits: Using Model Organisms to Study Gene-Gene Interactions

    PubMed Central

    Mackay, Trudy F. C.

    2014-01-01

    Summary The role of epistasis in the genetic architecture of quantitative traits is controversial, despite the biological plausibility that non-linear molecular interactions underpin the genotype-phenotype map. This controversy arises because most genetic variation for quantitative traits is additive. However, additive variance is consistent with pervasive epistatic gene action. Here, I discuss experimental designs to detect the contribution of epistasis to quantitative trait phenotypes in model organisms. These studies indicate that epistatic gene action is common, and that additivity can be an emergent property of underlying genetic interaction networks. Epistasis causes hidden quantitative genetic variation in natural populations and could be responsible for the small additive effects, missing heritability and lack of replication typically observed for human complex traits. PMID:24296533

  20. Adaptive phenotypic plasticity and plant water use

    Microsoft Academic Search

    Adrienne B. NicotraA; Amy DavidsonA

    2010-01-01

    The emergence of new techniques in plant science, including molecular and phenomic tools, presents a novel opportunitytore-evaluatethewayweexaminethephenotype.Ourincreasingcapacityforphenotypingmeansthatnotonly canweconsiderincreasingnumbersofspeciesorvarieties,butalsothatwecaneffectivelyquantifythephenotypesofthese differentgenotypesunderarangeofenvironmentalconditions.Thephenotypicplasticityofagivengenotype,ortherangeof phenotypes, that can be expressed dependent upon environment becomes something we can feasibly assess. Of particular importance is phenotypic variation that increases fitness or survival - adaptive phenotypic plasticity. Here, we examine the case of adaptive phenotypic plasticity in plant water

  1. Precision phenotyping of biomass accumulation in triticale reveals temporal genetic patterns of regulation

    PubMed Central

    Busemeyer, Lucas; Ruckelshausen, Arno; Möller, Kim; Melchinger, Albrecht E.; Alheit, Katharina V.; Maurer, Hans Peter; Hahn, Volker; Weissmann, Elmar A.; Reif, Jochen C.; Würschum, Tobias

    2013-01-01

    To extend agricultural productivity by knowledge-based breeding and tailor varieties adapted to specific environmental conditions, it is imperative to improve our ability to assess the dynamic changes of the phenome of crops under field conditions. To this end, we have developed a precision phenotyping platform that combines various sensors for a non-invasive, high-throughput and high-dimensional phenotyping of small grain cereals. This platform yielded high prediction accuracies and heritabilities for biomass of triticale. Genetic variation for biomass accumulation was dissected with 647 doubled haploid lines derived from four families. Employing a genome-wide association mapping approach, two major quantitative trait loci (QTL) for biomass were identified and the genetic architecture of biomass accumulation was found to be characterized by dynamic temporal patterns. Our findings highlight the potential of precision phenotyping to assess the dynamic genetics of complex traits, especially those not amenable to traditional phenotyping. PMID:23942574

  2. LE JOURNAL DE PHYSIQUE LES VARIATIONS DE LA QUANTIT D'OZONE CONTENUE DANS L'ATMOSPHRE

    E-print Network

    Paris-Sud XI, Université de

    LE JOURNAL DE PHYSIQUE ET LE RADIUM LES VARIATIONS DE LA QUANTITÉ D'OZONE CONTENUE DANS L'épaisseur de la couche d'ozone et les variations de la pression atmo- sphérique locale, d'ailleurs faibles'épaisseur de la couche d'ozone à partir des mesures de transparence de l'atmosphère dans le spectre visible

  3. Using height association studies to gain insights into human idiopathic short and syndromic stature phenotypes.

    PubMed

    Lettre, Guillaume

    2013-04-01

    Variation in adult height is not the most clinically relevant human quantitative trait, yet its study provides the foundation of many quantitative genetics theories and important statistical concepts (e.g. regression). Even today, the analysis of adult height by genome-wide association studies (GWAS) continues to significantly impact human genetics: these studies have led to the discovery of >200 loci associated with variation in adult height and have highlighted the very polygenic nature of human continuous traits. In this brief review, I discuss and provide examples on how such genetic associations, identified in individuals of normal height, could help understand the complex genetics behind such phenotypes as idiopathic short stature (ISS) or extreme/syndromic height phenotypes of unknown cause. PMID:22941042

  4. Explaining Quantitative Variation in the Rate of Optional Infinitive Errors across Languages: A Comparison of MOSAIC and the Variational Learning Model

    ERIC Educational Resources Information Center

    Freudenthal, Daniel: Pine, Julian; Gobet, Fernando

    2010-01-01

    In this study, we use corpus analysis and computational modelling techniques to compare two recent accounts of the OI stage: Legate & Yang's (2007) Variational Learning Model and Freudenthal, Pine & Gobet's (2006) Model of Syntax Acquisition in Children. We first assess the extent to which each of these accounts can explain the level of OI errors…

  5. Genome-Wide Association Analysis with Gray Matter Volume as a Quantitative Phenotype in First-Episode Treatment-Naïve Patients with Schizophrenia

    PubMed Central

    Deng, Wei; Wu, Junyao; Li, Mingli; Ma, Xiaohong; Wang, Yingcheng; Jiang, Lijun; McAlonan, Grainne; Chua, Siew E.; Sham, Pak C.; Hu, Xun; Li, Tao

    2013-01-01

    Reduced Gray matter (GM) volume is a core feature of schizophrenia. Mapping genes that is associated with the heritable disease-related phenotypes may be conducive to elucidate the pathogenesis of schizophrenia. This study aims to identify the common genetic variants that underlie the deficits of GM volume in schizophrenia. High-resolution T1 images and whole genome genotyping data were obtained from 74 first-episode treatment-naïve patients with schizophrenia and 51 healthy controls in the Mental Health Centre of the West China Hospital, Sichuan University. All participants were scanned using a 3T MR imaging system and were genotyped using the HumanHap660 Bead Array. Reduced GM volumes in three brain areas including left hOC3v in the collateral sulcus of visual cortex (hOC3vL), left cerebellar vermis lobule 10 (vermisL10) and right cerebellar vermis lobule 10 (vermisR10) were found in patients with schizophrenia. There was a group by genotype interaction when genotypes from genome-wide scan were subsequently considered in the case-control analyses. SNPs from three genes or chromosomal regions (TBXAS1, PIK3C2G and HS3ST5) were identified to predict the changes of GM volume in hOC3vL, vermisL10 and vermisR10. These results also highlighted the usefulness of endophenotype in exploring the pathogenesis of neuropsychiatric diseases such as schizophrenia although further independent replication studies are needed in the future. PMID:24086445

  6. Exploiting Gene Expression Variation to Capture Gene-Environment Interactions for Disease

    PubMed Central

    Idaghdour, Youssef; Awadalla, Philip

    2013-01-01

    Gene-environment interactions have long been recognized as a fundamental concept in evolutionary, quantitative, and medical genetics. In the genomics era, study of how environment and genome interact to shape gene expression variation is relevant to understanding the genetic architecture of complex phenotypes. While genetic analysis of gene expression variation focused on main effects, little is known about the extent of interaction effects implicating regulatory variants and their consequences on transcriptional variation. Here we survey the current state of the concept of transcriptional gene-environment interactions and discuss its utility for mapping disease phenotypes in light of the insights gained from genome-wide association studies of gene expression. PMID:23755064

  7. Does natural selection alter genetic architecture? An evaluation of quantitative genetic variation among populations of Allonemobiussocius and A. fasciatus

    Microsoft Academic Search

    Roff; Mousseau

    1999-01-01

    To make long-term predictions using present quantitative genetic theory it is necessary to assume that the genetic variance-covariance matrix (G) remains constant or at least changes by a constant fraction. In this paper we examine the stability of the genetic architecture of two traits known to be subject to natural selection; femur length and ovipositor length in two species of

  8. Understanding Variation in Treatment Effects in Education Impact Evaluations: An Overview of Quantitative Methods. NCEE 2014-4017

    ERIC Educational Resources Information Center

    Schochet, Peter Z.; Puma, Mike; Deke, John

    2014-01-01

    This report summarizes the complex research literature on quantitative methods for assessing how impacts of educational interventions on instructional practices and student learning differ across students, educators, and schools. It also provides technical guidance about the use and interpretation of these methods. The research topics addressed…

  9. Quantitative genetic analysis of brain size variation in sticklebacks: support for the mosaic model of brain evolution.

    PubMed

    Noreikiene, Kristina; Herczeg, Gábor; Gonda, Abigél; Balázs, Gergely; Husby, Arild; Merilä, Juha

    2015-07-01

    The mosaic model of brain evolution postulates that different brain regions are relatively free to evolve independently from each other. Such independent evolution is possible only if genetic correlations among the different brain regions are less than unity. We estimated heritabilities, evolvabilities and genetic correlations of relative size of the brain, and its different regions in the three-spined stickleback (Gasterosteus aculeatus). We found that heritabilities were low (average h(2) = 0.24), suggesting a large plastic component to brain architecture. However, evolvabilities of different brain parts were moderate, suggesting the presence of additive genetic variance to sustain a response to selection in the long term. Genetic correlations among different brain regions were low (average rG = 0.40) and significantly less than unity. These results, along with those from analyses of phenotypic and genetic integration, indicate a high degree of independence between different brain regions, suggesting that responses to selection are unlikely to be severely constrained by genetic and phenotypic correlations. Hence, the results give strong support for the mosaic model of brain evolution. However, the genetic correlation between brain and body size was high (rG = 0.89), suggesting a constraint for independent evolution of brain and body size in sticklebacks. PMID:26108633

  10. Phenotyping Bleeding

    PubMed Central

    James, Paula; Coller, Barry S.

    2013-01-01

    Purpose of review Although recorded evidence of phenotyping bleeding disorders extends back two millennia, standardization of phenotyping has only begun in the past half century. This was spurred by the need for greater precision in diagnosing disorders in order to select proper laboratory tests and treatment, and the realization that the bleeding history provides prognostic information about the future risk of bleeding with surgery or invasive procedures. Recent findings New bleeding assessment tools (BATs) have been developed to: 1. evaluate the relative bleeding risks associated with new anticoagulants and antiplatelet agents, 2. assess the efficacy of new thrombopoiesis stimulating agents in preventing hemorrhage in patients with immune thrombocytopenia, and 3. assess complex gene-gene and gene-environment interactions. New web-based systems allow many researchers to collaborate by sharing the same electronic phenotyping infrastructure. Major issues of validation remain, but at present, the data indicate that the new BATs have relatively high negative predictive value for excluding a significant bleeding disorder, but disappointingly low positive predictive values. Summary New instruments to phenotype bleeding have been developed to address a number of different important clinical and research goals. The improved standardization and opportunities for collaborative studies hold promise for maximizing diagnostic, prognostic, and scientific information. PMID:22759628

  11. Shift in phenotypic variation coupled with rapid loss of genetic diversity in captive populations of Eristalis tenax (Diptera: Syrphidae): consequences for rearing and potential commercial use.

    PubMed

    Francuski, Ljubinka; Djurakic, Marko; Ludoski, Jasmina; Hurtado, Pilar; Pérez-Bañón, Celeste; Ståhls, Gunilla; Rojo, Santos; Milankov, Vesna

    2014-04-01

    Because of its importance as a pollinator and its potential economic usefulness for the biodegradation of organic animal waste, the genetic and phenotypic diversity of the drone fly, Eristalis tenax L. (Diptera: Syrphidae), was studied in both wild and captive populations from southeastern Europe. Wild specimens from a natural protected habitat (with low human impact), field crop habitat (semisynanthropic condition), and intensive pig farming habitat (synanthropic condition) were compared with a laboratory colony reared on artificial media An integrative approach was applied based on allozyme loci, cytochrome c oxidase I mitochondrial DNA, wing traits (size and shape), and abdominal color patterns. Our results indicate that the fourth and eighth generations of the laboratory colony show a severe lack of genetic diversity compared with natural populations. Reduced genetic diversity in subsequent generations (F4 and F8) of the laboratory colony was found to be linked with phenotypic divergence. Loss of genetic variability associated with phenotypic differentiation in laboratory samples suggests a founder effect, followed by stochastic genetic processes and inbreeding. Hence, our results have implications for captive bred Eristalis flies, which have been used in crop pollination and biodegradation of organic waste under synanthropic conditions. PMID:24772566

  12. Detection and quantitation of single nucleotide polymorphisms, DNA sequence variations, DNA mutations, DNA damage and DNA mismatches

    DOEpatents

    McCutchen-Maloney, Sandra L. (Pleasanton, CA)

    2002-01-01

    DNA mutation binding proteins alone and as chimeric proteins with nucleases are used with solid supports to detect DNA sequence variations, DNA mutations and single nucleotide polymorphisms. The solid supports may be flow cytometry beads, DNA chips, glass slides or DNA dips sticks. DNA molecules are coupled to solid supports to form DNA-support complexes. Labeled DNA is used with unlabeled DNA mutation binding proteins such at TthMutS to detect DNA sequence variations, DNA mutations and single nucleotide length polymorphisms by binding which gives an increase in signal. Unlabeled DNA is utilized with labeled chimeras to detect DNA sequence variations, DNA mutations and single nucleotide length polymorphisms by nuclease activity of the chimera which gives a decrease in signal.

  13. A Quantitative-Trait Genome-Wide Association Study of Alcoholism Risk in the Community: Findings and

    E-print Network

    Nyholt, Dale R.

    A Quantitative-Trait Genome-Wide Association Study of Alcoholism Risk in the Community: Findings contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high) for phenotypes related to alcohol use and dependence. Methods: Diagnostic interview and blood/buccal samples were

  14. Outdoor continuous culture of Porphyridium cruentum in a tubular photobioreactor: quantitative analysis of the daily cyclic variation of culture parameters

    Microsoft Academic Search

    M. M. Rebolloso Fuentes; J. L. Garc??a Sánchez; J. M. Fernández Sevilla; F. G. Acién Fernández; J. A. Sánchez Pérez; E. Molina Grima

    1999-01-01

    The present work reports on the daily cyclic variation of oxygen generation rates, carbon consumption rates, photosynthetic activities, growth rates and biochemical composition of the biomass in a pilot plant continuous outdoor culture of the microalgae Porphyridium cruentum. A linear relationship between the external irradiance and the average irradiance inside the culture was found. In addition, the oxygen generation and

  15. Comparing Label-Free Quantitative Peptidomics Approaches to Characterize Diurnal Variation of Peptides in the Rat Suprachiasmatic

    E-print Network

    Gillette, Martha U.

    of Peptides in the Rat Suprachiasmatic Nucleus Bruce R. Southey, Ji Eun Lee,, Leonid Zamdborg, Norman Atkins, peptidomic analyses from two times of day were examined to characterize variation in SCN peptides using three peptides, 207 peptides were analyzed by two label-free methods, spectral count and spectral index

  16. Relaxed selection is a precursor to the evolution of phenotypic plasticity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenotypic plasticity represents one of the most important ways that organisms adaptively respond to environmental variation. Alternate phenotypes produced through phenotypic plasiticity generally arise through conditional gene expression, which is predicted to result in relaxed selective constrain...

  17. Phenotypic divergence of the common toad (Bufo bufo) along an altitudinal gradient: evidence for local adaptation.

    PubMed

    Luquet, E; Léna, J-P; Miaud, C; Plénet, S

    2015-01-01

    Variation in the environment can induce different patterns of genetic and phenotypic differentiation among populations. Both neutral processes and selection can influence phenotypic differentiation. Altitudinal phenotypic variation is of particular interest in disentangling the interplay between neutral processes and selection in the dynamics of local adaptation processes but remains little explored. We conducted a common garden experiment to study the phenotypic divergence in larval life-history traits among nine populations of the common toad (Bufo bufo) along an altitudinal gradient in France. We further used correlation among population pairwise estimates of quantitative trait (QST) and neutral genetic divergence (FST from neutral microsatellite markers), as well as altitudinal difference, to estimate the relative role of divergent selection and neutral genetic processes in phenotypic divergence. We provided evidence for a neutral genetic differentiation resulting from both isolation by distance and difference in altitude. We found evidence for phenotypic divergence along the altitudinal gradient (faster development, lower growth rate and smaller metamorphic size). The correlation between pairwise QSTs-FSTs and altitude differences suggested that this phenotypic differentiation was most likely driven by altitude-mediated selection rather than by neutral genetic processes. Moreover, we found different divergence patterns for larval traits, suggesting that different selective agents may act on these traits and/or selection on one trait may constrain the evolution on another through genetic correlation. Our study highlighted the need to design more integrative studies on the common toad to unravel the underlying processes of phenotypic divergence and its selective agents in the context of environmental clines. PMID:25074572

  18. Chimeric proteins for detection and quantitation of DNA mutations, DNA sequence variations, DNA damage and DNA mismatches

    DOEpatents

    McCutchen-Maloney, Sandra L. (Pleasanton, CA)

    2002-01-01

    Chimeric proteins having both DNA mutation binding activity and nuclease activity are synthesized by recombinant technology. The proteins are of the general formula A-L-B and B-L-A where A is a peptide having DNA mutation binding activity, L is a linker and B is a peptide having nuclease activity. The chimeric proteins are useful for detection and identification of DNA sequence variations including DNA mutations (including DNA damage and mismatches) by binding to the DNA mutation and cutting the DNA once the DNA mutation is detected.

  19. A Quantitative Model of Motility Reveals Low-Dimensional Variation in Exploratory Behavior Across Multiple Nematode Species

    NASA Astrophysics Data System (ADS)

    Helms, Stephen; Avery, Leon; Stephens, Greg; Shimizu, Tom

    2014-03-01

    Animal behavior emerges from many layers of biological organization--from molecular signaling pathways and neuronal networks to mechanical outputs of muscles. In principle, the large number of interconnected variables at each of these layers could imply dynamics that are complex and hard to control or even tinker with. Yet, for organisms to survive in a competitive, ever-changing environment, behavior must readily adapt. We applied quantitative modeling to identify important aspects of behavior in chromadorean nematodes ranging from the lab strain C. elegans N2 to wild strains and distant species. We revealed subtle yet important features such as speed control and heavy-tailed directional changes. We found that the parameters describing this behavioral model varied among individuals and across species in a correlated way that is consistent with a trade-off between exploratory and exploitative behavior.

  20. Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across two abiotic environmental gradients in Poecilia mexicana.

    PubMed

    Tobler, Michael; Dewitt, Thomas J; Schlupp, Ingo; García de León, Francisco J; Herrmann, Roger; Feulner, Philine G D; Tiedemann, Ralph; Plath, Martin

    2008-10-01

    Divergent natural selection drives evolutionary diversification. It creates phenotypic diversity by favoring developmental plasticity within populations or genetic differentiation and local adaptation among populations. We investigated phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along two abiotic environmental gradients. These fish typically inhabit nonsulfidic surface rivers, but also colonized sulfidic and cave habitats. We assessed phenotypic variation among a factorial combination of habitat types using geometric and traditional morphometrics, and genetic divergence using quantitative and molecular genetic analyses. Fish in caves (sulfidic or not) exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface or cave) exhibited larger heads and longer gill filaments. Common-garden rearing suggested that these morphological differences are partly heritable. Population genetic analyses using microsatellites as well as cytochrome b gene sequences indicate high population differentiation over small spatial scale and very low rates of gene flow, especially among different habitat types. This suggests that divergent environmental conditions constitute barriers to gene flow. Strong molecular divergence over short distances as well as phenotypic and quantitative genetic divergence across habitats in directions classic to fish ecomorphology suggest that divergent selection is structuring phenotypic variation in this system. PMID:18637957

  1. Phenotypic plasticity and genotype by environment interaction for olfactory behavior in Drosophila melanogaster.

    PubMed

    Sambandan, Deepa; Carbone, Mary Anna; Anholt, Robert R H; Mackay, Trudy F C

    2008-06-01

    Genotype by environment interactions (GEI) play a major part in shaping the genetic architecture of quantitative traits and are confounding factors in genetic studies, for example, in attempts to associate genetic variation with disease susceptibility. It is generally not known what proportion of phenotypic variation is due to GEI and how many and which genes contribute to GEI. Behaviors are complex traits that mediate interactions with the environment and, thus, are ideally suited for studies of GEI. Olfactory behavior in Drosophila melanogaster presents an opportunity to systematically dissect GEI, since large numbers of genetically identical individuals can be reared under defined environmental conditions and the olfactory system of Drosophila and its behavioral response to odorants have been well characterized. We assessed variation in olfactory behavior in a population of 41 wild-derived inbred lines and asked to what extent different larval-rearing environments would influence adult olfactory behavior and whether GEI is a minor or major contributing source of phenotypic variation. We found that approximately 50% of phenotypic variation in adult olfactory behavior is attributable to GEI. In contrast, transcriptional analysis revealed that only 20 genes show GEI at the level of gene expression [false discovery rate (FDR) < 0.05], some of which are associated with physiological responses to environmental chemicals. Quantitative complementation tests with piggyBac-tagged mutants for 2 of these genes (CG9664 and Transferrin 1) demonstrate that genes that show transcriptional GEI are candidate genes for olfactory behavior and that GEI at the level of gene expression is correlated with GEI at the level of phenotype. PMID:18505870

  2. On the capability of Swarm for surface mass variation monitoring: Quantitative assessment based on orbit information from CHAMP, GRACE and GOCE

    NASA Astrophysics Data System (ADS)

    Baur, Oliver; Weigelt, Matthias; Zehentner, Norbert; Mayer-Gürr, Torsten; Jäggi, Adrian

    2014-05-01

    In the last decade, temporal variations of the gravity field from GRACE observations have become one of the most ubiquitous and valuable sources of information for geophysical and environmental studies. In the context of global climate change, mass balance of the Arctic and Antarctic ice sheets gained particular attention. Because GRACE has outlived its predicted lifetime by several years already, it is very likely that a gap between GRACE and its successor GRACE follow-on (supposed to be launched in 2017, at the earliest) occurs. The Swarm mission - launched on November 22, 2013 - is the most promising candidate to bridge this potential gap, i.e., to directly acquire large-scale mass variation information on the Earth's surface in case of a gap between the present GRACE and the upcoming GRACE follow-on projects. Although the magnetometry mission Swarm has not been designed for gravity field purposes, its three satellites have the characteristics for such an endeavor: (i) low, near-circular and near-polar orbits, (ii) precise positioning with high-quality GNSS receivers, (iii) on-board accelerometers to measure the influence of non-gravitational forces. Hence, from an orbit analysis point of view the Swarm satellites are comparable to the CHAMP, GRACE and GOCE spacecraft. Indeed and as data analysis from CHAMP has been shown, the detection of annual signals and trends from orbit analysis is possible for long-wavelength features of the gravity field, although the accuracy associated with the inter-satellite GRACE measurements cannot be reached. We assess the capability of the (non-dedicated) mission Swarm for mass variation detection in a real-case environment (opposed to simulation studies). For this purpose, we "approximate" the Swarm scenario by the GRACE+CHAMP and GRACE+GOCE constellations. In a first step, kinematic orbits of the individual satellites are derived from GNSS observations. From these orbits, we compute monthly combined GRACE+CHAMP and GRACE+GOCE time-variable gravity fields; sophisticated techniques based on Kalman filtering are applied to reduce noise in the time series. Finally, we infer mass variation in selected areas from to gravity signal. These results are compared to the findings obtained from mass variation detection exploiting CSR-RL05 gravity fields; due to their superior quality (which is due to the fact that they are derived from inter-satellite GRACE measurements), the CSR-RL05 solutions serve as benchmark. Our quantitative assessment shows the potential and limitations of what can be expected from Swarm with regard to surface mass variation monitoring.

  3. A quantitative trait locus on Bos taurus autosome 17 explains a large proportion of the genetic variation in de novo synthesized milk fatty acids.

    PubMed

    Duchemin, S I; Visker, M H P W; Van Arendonk, J A M; Bovenhuis, H

    2014-11-01

    A genomic region associated with milk fatty acid (FA) composition has been detected on Bos taurus autosome (BTA)17 based on 50,000 (50K) single nucleotide polymorphism (SNP) genotypes. The aim of our study was to fine-map BTA17 with imputed 777,000 (777 K) SNP genotypes to identify candidate genes associated with milk FA composition. Phenotypes consisted of gas chromatography measurements of 14 FA based on winter and summer milk samples. Phenotypes and genotypes were available on 1,640 animals in winter milk, and on 1,581 animals in summer milk samples. Single-SNP analyses showed that several SNP in a region located between 29.0 and 34.0 Mbp were in strong association with C6:0, C8:0, and C10:0. This region was further characterized based on haplotypes. In summer milk samples, for example, these haplotypes explained almost 10% of the genetic variance in C6:0, 9% in C8:0, 3.5% in C10:0, 1.8% in C12:0, and 0.9% in C14:0. Two groups of haplotypes with distinct predicted effects could be defined, suggesting the presence of one causal variant. Predicted haplotype effects tended to increase from C6:0 to C14:0; however, the proportion of genetic variance explained by the haplotypes tended to decrease from C6:0 to C14:0. This is an indication that the quantitative trait locus (QTL) region is involved either in the elongation process or in early termination of de novo synthesized FA. Although many genes are present in this QTL region, most of these genes on BTA17 have not been characterized yet. The strongest association was found close to the progesterone receptor membrane component 2 (PGRMC2) gene, which has not yet been associated with milk FA composition. Therefore, no clear candidate gene associated with milk FA composition could be identified for this QTL. PMID:25242430

  4. Capillary zone electrophoresis and capillary electrophoresis-mass spectrometry for analyzing qualitative and quantitative variations in therapeutic albumin.

    PubMed

    Marie, Anne-Lise; Przybylski, Cédric; Gonnet, Florence; Daniel, Régis; Urbain, Rémi; Chevreux, Guillaume; Jorieux, Sylvie; Taverna, Myriam

    2013-10-24

    The present study describes a reproducible and quantitative capillary zone electrophoresis (CZE) method, which leads to the separation of nine forms (native, oxidized and glycated) of human serum albumin (HSA). In an attempt to identify the different species separated by this CZE method, the capillary electrophoresis was coupled to mass spectrometry using a sheath liquid interface, an optimized capillary coating and a suitable CE running buffer. CE-MS analyses confirmed the heterogeneity of albumin preparation and revealed new truncated and modified forms such as Advanced Glycation End products (AGEs). Assignment of the CZE peaks was carried out using specific antibodies, carboxypeptidase A or sample reduction before or during the CE separation. Thus, five HSA forms were unambiguously identified. Using this CZE method several albumin batches produced by slightly different fractionation ways could be discriminated. Furthermore, analyses of HSA preparations marketed by five pharmaceutical industries revealed that two therapeutic albumins, including that marketed by LFB, contained the highest proportion of native form and lower levels of oxidized forms. PMID:24120174

  5. Quantitative genetics of pigmentation development in 2 populations of the common garter snake, Thamnophis sirtalis.

    PubMed

    Westphal, Michael F; Morgan, Theodore J

    2010-01-01

    The evolutionary importance of ontogenetic change has been noted since Darwin. However, most analyses of phenotypic evolution focus on single landmark ages. Here, we present an inheritance study that quantifies genetic variation in pigmentation across early-age (i.e., birth to 180 days) development in 2 populations of the common garter snake, Thamnophis sirtalis. The populations are phenotypically distinct and geographically isolated (Manitoba, CA and Northern California, USA). There were highly significant differences between populations for the developmental trajectory of mean pigmentation, with the Manitoba population exhibiting a mean pigmentation level that increased across ontogeny, whereas the California population exhibited mean pigmentation that was invariant across ontogeny. Subsequent quantitative genetic analyses revealed heritable variation at all ages in Manitoba but low levels of phenotypic and genetic variation in California at all ages. A quantitative genetic decomposition of the longitudinal genetic variance-covariance matrix for the age-specific pigmentation phenotypes in the Manitoba population revealed 2 primary orthogonal axes that explained most ( approximately 100%) of the pigmentation variation across ontogeny. The primary axis, explaining 93% of the genetic variation, is an axis of genetic variation whose principal value loadings change from positive to negative across development, suggesting that the most rapid evolutionary response to selection on pigmentation variation will occur in the direction characterized by a tradeoff in early-age versus late-age pigmentation phenotypes. Pigmentation is known to be ecologically important and subject to rapid evolution under selection. Our study shows that significant differences exist between these 2 populations for their capacity to respond to selection on pigmentation which is not only influenced by the population of origin but also by the developmental process. We suggest that developmental timing may be a potential explanatory mechanism for the difference between the populations. PMID:20453034

  6. Evolution of phenotypic plasticity in colonizing species.

    PubMed

    Lande, Russell

    2015-05-01

    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life. PMID:25558898

  7. Vanaso is a candidate quantitative trait gene for Drosophila olfactory behavior.

    PubMed Central

    Fanara, Juan José; Robinson, Kellie O; Rollmann, Stephanie M; Anholt, Robert R H; Mackay, Trudy F C

    2002-01-01

    Most animals depend on olfaction for survival and procreation. Odor-guided behavior is a quantitative trait, with phenotypic variation due to multiple segregating quantitative trait loci (QTL). Despite its profound biological importance, the genetic basis of naturally occurring variation in olfactory behavior remains unexplored. Here, we mapped a single Drosophila QTL affecting variation in avoidance response to benzaldehyde, using a population of recombinant inbred lines. Deficiency complementation mapping resolved this region into one female- and one male-specific QTL. Subsequent quantitative complementation tests to all available mutations of positional candidate genes showed that the female-specific QTL failed to complement a P-element insertional mutation, l(3)04276. The P-element insertion was in the intron of a novel gene, Vanaso, which contains a putative guanylate binding protein domain, is highly polymorphic, and is expressed in the third antennal segment, the major olfactory organ of Drosophila. No expression was detected in the fly brain, suggesting that Vanaso plays a role in peripheral chemosensory processes rather than in central integration of olfactory information. QTL mapping followed by quantitative complementation tests to deficiencies and mutations is an effective strategy for gene discovery that allows characterization of effects of recessive lethal genes on adult phenotypes and here enabled identification of a candidate gene that contributes to sex-specific quantitative variation in olfactory behavior. PMID:12454076

  8. Quantitative assessment of single-cell whole genome amplification methods for detecting copy number variation using hippocampal neurons.

    PubMed

    Ning, Luwen; Li, Zhoufang; Wang, Guan; Hu, Wen; Hou, Qingming; Tong, Yin; Zhang, Meng; Chen, Yao; Qin, Li; Chen, Xiaoping; Man, Heng-Ye; Liu, Pinghua; He, Jiankui

    2015-01-01

    Single-cell genomic analysis has grown rapidly in recent years and finds widespread applications in various fields of biology, including cancer biology, development, immunology, pre-implantation genetic diagnosis, and neurobiology. To date, the amplification bias, amplification uniformity and reproducibility of the three major single cell whole genome amplification methods (GenomePlex WGA4, MDA and MALBAC) have not been systematically investigated using mammalian cells. In this study, we amplified genomic DNA from individual hippocampal neurons using three single-cell DNA amplification methods, and sequenced them at shallow depth. We then systematically evaluated the GC-bias, reproducibility, and copy number variations among individual neurons. Our results showed that single-cell genome sequencing results obtained from the MALBAC and WGA4 methods are highly reproducible and have a high success rate. The MALBAC displays significant biases towards high GC content. We then attempted to correct the GC bias issue by developing a bioinformatics pipeline, which allows us to call CNVs in single cell sequencing data, and chromosome level and sub-chromosomal level CNVs among individual neurons can be detected. We also proposed a metric to determine the CNV detection limits. Overall, MALBAC and WGA4 have better performance than MDA in detecting CNVs. PMID:26091148

  9. Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype

    PubMed Central

    Etemadi, Arash; Islami, Farhad; Phillips, David H.; Godschalk, Roger; Golozar, Asieh; Kamangar, Farin; Malekshah, Akbar Fazel-Tabar; Pourshams, Akram; Elahi, Seerat; Ghojaghi, Farhad; Strickland, Paul T; Taylor, Philip R; Boffetta, Paolo; Abnet, Christian C; Dawsey, Sanford M; Malekzadeh, Reza; van Schooten, Frederik J.

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even in never-smokers. We tried to find a model to explain the relationship between variation in PAH-related DNA adduct levels among people with similar exposures, multiple genetic polymorphisms in genes related to metabolic and repair pathways, and nucleotide excision repair (NER) capacity. In 111 randomly-selected female never-smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in 8 DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by 32P-postlabelling. Multivariable regression models were compared by Akaike’s information criterion (AIC). Aromatic DNA adduct levels ranged between 1.7 and 18.6 per 108 nucleotides (mean: 5.8±3.1). DNA adduct level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non risk-allele genotype, and was higher in the MPO homozygote risk-allele genotype. The sum of risk alleles in these genes significantly correlated with the log-adduct level (r=0.4, p<0.001). Compared with the environmental model, adding phase I SNPs and NER capacity provided the best fit, and could explain 17% more of the variation in adduct levels. NER capacity was affected by polymorphisms in the MTHFR and ERCC1 genes. Female non-smokers in this population had PAH-related DNA adduct levels 3-4 times higher than smokers and occupationally-exposed groups in previous studies, with large inter-individual variation which could best be explained by a combination of phase I genes and NER capacity. PMID:23175176

  10. On the mechanism of seasonal and solar cycle NmF2 variations: A quantitative estimate of the main parameters contribution using incoherent scatter radar observations

    NASA Astrophysics Data System (ADS)

    Mikhailov, A. V.; Perrone, L.

    2011-03-01

    Seasonal (winter/summer) and solar cycle NmF2 variations as well as summer saturation effect in NmF2 have been analyzed using Millstone Hill incoherent scatter radar (ISR) daytime observations. A self-consistent approach to the Ne(h) modeling has been applied to extract from ISR observations a consistent set of main aeronomic parameters and to estimate their quantitative contribution to the observed NmF2 variations. The retrieved aeronomic parameters are independent of uncertainties in thermosphere and solar EUV empirical models, and this is a distinguishing feature of the present consideration. Different temperatures in winter and in summer in the course of solar cycle overlapped on the O+ + N2 reaction rate coefficient temperature dependence result in different NmF2 dependences on solar activity: a steep practically linear increase with a tendency to turn up in January (contrary to international reference ionosphere prediction) and a slow increase with a tendency to saturate at high solar activity in July despite increasing solar EUV irradiation. In winter the EUV flux and thermospheric parameters provide approximately equal contributions to the NmF2 increase, while in summer the contribution of thermospheric parameters is small. Both in winter and in summer the variations of atomic oxygen [O] are small at the F2 layer peak, and its contribution is small compared to linear loss coefficient, ?. It is shown that the summer saturation effect in NmF2 under high solar activity is not just reduced to O/N2 or EUV flux solar cycle variations but is determined by ? via the ?1 temperature dependence. A new mechanism (qualitative) to explain the December anomaly in NmF2 is proposed. It is based on the idea that the areas of atomic oxygen production and its loss are spatially separated and that time is required to transfer [O] from one area to the other where [O] associates in a three-body collision. Therefore, under a 7% increase in the O2 dissociation rate due to the Sun-Earth distance decrease in December-January compared to June-July, an accumulation of atomic oxygen should take place in the thermosphere in the vicinity of the December solstice resulting in a 21% NmF2 increase, which is close to the observed global December effect.

  11. Allelic variants of the amylose extender mutation of maize demonstrate phenotypic variation in starch structure resulting from modified protein-protein interactions.

    PubMed

    Liu, Fushan; Ahmed, Zaheer; Lee, Elizabeth A; Donner, Elizabeth; Liu, Qiang; Ahmed, Regina; Morell, Matthew K; Emes, Michael J; Tetlow, Ian J

    2012-02-01

    Amylose extender (ae(-)) starches characteristically have modified starch granule morphology resulting from amylopectin with reduced branch frequency and longer glucan chains in clusters, caused by the loss of activity of the major starch branching enzyme (SBE), which in maize endosperm is SBEIIb. A recent study with ae(-) maize lacking the SBEIIb protein (termed ae1.1 herein) showed that novel protein-protein interactions between enzymes of starch biosynthesis in the amyloplast could explain the starch phenotype of the ae1.1 mutant. The present study examined an allelic variant of the ae(-) mutation, ae1.2, which expresses a catalytically inactive form of SBEIIb. The catalytically inactive SBEIIb in ae1.2 lacks a 28 amino acid peptide (Val272-Pro299) and is unable to bind to amylopectin. Analysis of starch from ae1.2 revealed altered granule morphology and physicochemical characteristics distinct from those of the ae1.1 mutant as well as the wild-type, including altered apparent amylose content and gelatinization properties. Starch from ae1.2 had fewer intermediate length glucan chains (degree of polymerization 16-20) than ae1.1. Biochemical analysis of ae1.2 showed that there were differences in the organization and assembly of protein complexes of starch biosynthetic enzymes in comparison with ae1.1 (and wild-type) amyloplasts, which were also reflected in the composition of starch granule-bound proteins. The formation of stromal protein complexes in the wild-type and ae1.2 was strongly enhanced by ATP, and broken by phosphatase treatment, indicating a role for protein phosphorylation in their assembly. Labelling experiments with [?-(32)P]ATP showed that the inactive form of SBEIIb in ae1.2 was phosphorylated, both in the monomeric form and in association with starch synthase isoforms. Although the inactive SBEIIb was unable to bind starch directly, it was strongly associated with the starch granule, reinforcing the conclusion that its presence in the granules is a result of physical association with other enzymes of starch synthesis. In addition, an Mn(2+)-based affinity ligand, specific for phosphoproteins, was used to show that the granule-bound forms of SBEIIb in the wild-type and ae1.2 were phosphorylated, as was the granule-bound form of SBEI found in ae1.2 starch. The data strongly support the hypothesis that the complement of heteromeric complexes of proteins involved in amylopectin synthesis contributes to the fine structure and architecture of the starch granule. PMID:22121198

  12. Phenotypic plasticity of gas exchange pattern and water loss in Scarabaeus spretus (Coleoptera: Scarabaeidae): deconstructing the basis for metabolic rate variation.

    PubMed

    Terblanche, John S; Clusella-Trullas, Susana; Chown, Steven L

    2010-09-01

    Investigation of gas exchange patterns and modulation of metabolism provide insight into metabolic control systems and evolution in diverse terrestrial environments. Variation in metabolic rate in response to environmental conditions has been explained largely in the context of two contrasting hypotheses, namely metabolic depression in response to stressful or resource-(e.g. water) limited conditions, or elevation of metabolism at low temperatures to sustain life in extreme conditions. To deconstruct the basis for metabolic rate changes in response to temperature variation, here we undertake a full factorial study investigating the longer- and short-term effects of temperature exposure on gas exchange patterns. We examined responses of traits of gas exchange [standard metabolic rate (SMR); discontinuous gas exchange (DGE) cycle frequency; cuticular, respiratory and total water loss rate (WLR)] to elucidate the magnitude and form of plastic responses in the dung beetle, Scarabaeus spretus. Results showed that short- and longer-term temperature variation generally have significant effects on SMR and WLR. Overall, acclimation to increased temperature led to a decline in SMR (from 0.071+/-0.004 ml CO(2) h(-1) in 15 degrees C-acclimated beetles to 0.039+/-0.004 ml CO(2) h(-1) in 25 degrees C-acclimated beetles measured at 20 degrees C) modulated by reduced DGE frequency (15 degrees C acclimation: 0.554+/-0.027 mHz, 20 degrees C acclimation: 0.257+/-0.030 mHz, 25 degrees C acclimation: 0.208+/-0.027 mHz recorded at 20 degrees C), reduced cuticular WLRs (from 1.058+/-0.537 mg h(-1) in 15 degrees C-acclimated beetles to 0.900+/-0.400 mg h(-1) in 25 degrees C-acclimated beetles measured at 20 degrees C) and reduced total WLR (from 4.2+/-0.5 mg h(-1) in 15 degrees C-acclimated beetles to 3.1+/-0.5 mg h(-1) in 25 degrees C-acclimated beetles measured at 25 degrees C). Respiratory WLR was reduced from 2.25+/-0.40 mg h(-1) in 15 degrees C-acclimated beetles to 1.60+/-0.40 mg h(-1) in 25 degrees C-acclimated beetles measured at 25 degrees C, suggesting conservation of water during DGE bursts. Overall, this suggests water conservation is a priority for S. spretus exposed to longer-term temperature variation, rather than elevation of SMR in response to low temperature acclimation, as might be expected from a beetle living in a relatively warm, low rainfall summer region. These results are significant for understanding the evolution of gas exchange patterns and trade-offs between metabolic rate and water balance in insects and other terrestrial arthropods. PMID:20709922

  13. Quantitative trait loci affecting starvation resistance in Drosophila melanogaster.

    PubMed Central

    Harbison, Susan T; Yamamoto, Akihiko H; Fanara, Juan J; Norga, Koenraad K; Mackay, Trudy F C

    2004-01-01

    The ability to withstand periods of scarce food resources is an important fitness trait. Starvation resistance is a quantitative trait controlled by multiple interacting genes and exhibits considerable genetic variation in natural populations. This genetic variation could be maintained in the face of strong selection due to a trade-off in resource allocation between reproductive activity and individual survival. Knowledge of the genes affecting starvation tolerance and the subset of genes that affect variation in starvation resistance in natural populations would enable us to evaluate this hypothesis from a quantitative genetic perspective. We screened 933 co-isogenic P-element insertion lines to identify candidate genes affecting starvation tolerance. A total of 383 P-element insertions induced highly significant and often sex-specific mutational variance in starvation resistance. We also used deficiency complementation mapping followed by complementation to mutations to identify 12 genes contributing to variation in starvation resistance between two wild-type strains. The genes we identified are involved in oogenesis, metabolism, and feeding behaviors, indicating a possible link to reproduction and survival. However, we also found genes with cell fate specification and cell proliferation phenotypes, which implies that resource allocation during development and at the cellular level may also influence the phenotypic response to starvation. PMID:15126400

  14. Evolution of molecular phenotypes under stabilizing selection

    NASA Astrophysics Data System (ADS)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes.

  15. Phenotypic and Evolutionary Consequences of Social Behaviours: Interactions among Individuals Affect Direct Genetic Effects

    PubMed Central

    Trubenová, Barbora; Hager, Reinmar

    2012-01-01

    Traditional quantitative genetics assumes that an individual's phenotype is determined by both genetic and environmental factors. For many animals, part of the environment is social and provided by parents and other interacting partners. When expression of genes in social partners affects trait expression in a focal individual, indirect genetic effects occur. In this study, we explore the effects of indirect genetic effects on the magnitude and range of phenotypic values in a focal individual in a multi-member model analyzing three possible classes of interactions between individuals. We show that social interactions may not only cause indirect genetic effects but can also modify direct genetic effects. Furthermore, we demonstrate that both direct and indirect genetic effects substantially alter the range of phenotypic values, particularly when a focal trait can influence its own expression via interactions with traits in other individuals. We derive a function predicting the relative importance of direct versus indirect genetic effects. Our model reveals that both direct and indirect genetic effects can depend to a large extent on both group size and interaction strength, altering group mean phenotype and variance. This may lead to scenarios where between group variation is much higher than within group variation despite similar underlying genetic properties, potentially affecting the level of selection. Our analysis highlights key properties of indirect genetic effects with important consequences for trait evolution, the level of selection and potentially speciation. PMID:23226195

  16. A collective mechanism for phase variation in biofilms

    PubMed Central

    Chia, Nicholas; Woese, Carl R.; Goldenfeld, Nigel

    2008-01-01

    Understanding how microbes gather into biofilm communities and maintain diversity remains one of the central questions of microbiology, requiring an understanding of microbes as communal rather then individual organisms. Phase variation plays an integral role in the formation of diverse phenotypes within biofilms. We propose a collective mechanism for phase variation based on gene transfer agents, and apply the theory to predict the population structure and growth dynamics of a biofilm. Our results describe quantitatively recent experiments, with the only adjustable parameter being the rate of intercellular horizontal gene transfer. Our approach derives from a more general picture for the emergence of cooperation between microbes. PMID:18799735

  17. Untargeted Metabolic Quantitative Trait Loci Analyses Reveal a Relationship between Primary Metabolism and Potato Tuber Quality1[W][OA

    PubMed Central

    Carreno-Quintero, Natalia; Acharjee, Animesh; Maliepaard, Chris; Bachem, Christian W.B.; Mumm, Roland; Bouwmeester, Harro; Visser, Richard G.F.; Keurentjes, Joost J.B.

    2012-01-01

    Recent advances in -omics technologies such as transcriptomics, metabolomics, and proteomics along with genotypic profiling have permitted dissection of the genetics of complex traits represented by molecular phenotypes in nonmodel species. To identify the genetic factors underlying variation in primary metabolism in potato (Solanum tuberosum), we have profiled primary metabolite content in a diploid potato mapping population, derived from crosses between S. tuberosum and wild relatives, using gas chromatography-time of flight-mass spectrometry. In total, 139 polar metabolites were detected, of which we identified metabolite quantitative trait loci for approximately 72% of the detected compounds. In order to obtain an insight into the relationships between metabolic traits and classical phenotypic traits, we also analyzed statistical associations between them. The combined analysis of genetic information through quantitative trait locus coincidence and the application of statistical learning methods provide information on putative indicators associated with the alterations in metabolic networks that affect complex phenotypic traits. PMID:22223596

  18. Quantitative PCR Reveals Strong Spatial and Temporal Variation of the Wasting Disease Pathogen, Labyrinthula zosterae in Northern European Eelgrass (Zostera marina) Beds

    PubMed Central

    Bockelmann, Anna-Christina; Tams, Verena; Ploog, Jana; Schubert, Philipp R.; Reusch, Thorsten B. H.

    2013-01-01

    Seagrass beds are the foundation species of functionally important coastal ecosystems worldwide. The world’s largest losses of the widespread seagrass Zostera marina (eelgrass) have been reported as a consequence of wasting disease, an infection with the endophytic protist Labyrinthula zosterae. During one of the most extended epidemics in the marine realm, ?90% of East and Western Atlantic eelgrass beds died-off between 1932 and 1934. Today, small outbreaks continue to be reported, but the current extent of L. zosterae in European meadows is completely unknown. In this study we quantify the abundance and prevalence of the wasting disease pathogen among 19 Z. marina populations in northern European coastal waters, using quantitative PCR (QPCR) with primers targeting a species specific portion of the internally transcribed spacer (ITS1) of L. zosterae. Spatially, we found marked variation among sites with abundances varying between 0 and 126 cells mg?1 Z. marina dry weight (mean: 5.7 L. zosterae cells mg?1 Z. marina dry weight ±1.9 SE) and prevalences ranged from 0–88.9%. Temporarily, abundances varied between 0 and 271 cells mg?1 Z. marina dry weight (mean: 8.5±2.6 SE), while prevalences ranged from zero in winter and early spring to 96% in summer. Field concentrations accessed via bulk DNA extraction and subsequent QPCR correlated well with prevalence data estimated via isolation and cultivation from live plant tissue. L. zosterae was not only detectable in black lesions, a sign of Labyrinthula-induced necrosis, but also occurred in green, apparently healthy tissue. We conclude that L. zosterae infection is common (84% infected populations) in (northern) European eelgrass populations with highest abundances during the summer months. In the light of global climate change and increasing rate of marine diseases our data provide a baseline for further studies on the causes of pathogenic outbreaks of L. zosterae. PMID:23658711

  19. Male fertility versus sterility, cytotype, and DNA quantitative variation in seed production in diploid and tetraploid sea lavenders (Limonium sp., Plumbaginaceae) reveal diversity in reproduction modes.

    PubMed

    Róis, Ana Sofia; Teixeira, Generosa; Sharbel, Timothy F; Fuchs, Jörg; Martins, Sérgio; Espírito-Santo, Dalila; Caperta, Ana D

    2012-12-01

    The genus Limonium Miller, a complex taxonomic group, comprises annuals and perennials that can produce sexual and/or asexual seeds (apomixis). In this study, we used diverse cytogenetic and cytometric approaches to analyze male sporogenesis and gametogenesis for characterizing male reproductive output on seed production in Limonium ovalifolium and Limonium multiflorum. We showed here that the first species is mostly composed of diploid cytotypes with 2n = 16 chromosomes and the latter species by tetraploid cytotypes with 2n = 32, 34, 35, 36 chromosomes and had a genome roughly twice as big as the former one. In both species, euploid and aneuploid cytotypes with large metacentric chromosomes having decondensed interstitial sites were found within and among populations, possibly involved in chromosomal reconstructions. L. ovalifolium diploids showed regular meiosis resulting in normal tetrads, while diverse chromosome pairing and segregation irregularities leading to the formation of abnormal meiotic products are found in balanced and non-balanced L. multiflorum tetraploids. Before anther dehiscence, the characteristic unicellular, bicellular, or tricellular pollen grains showing the typical Limonium micro- or macro-reticulate exine ornamentation patterns were observed in L. ovalifolium using scanning electron microscopy. Most of these grains were viable and able to produce pollen tubes in vitro. In both balanced and unbalanced L. multiflorum tetraploids, microspores only developed until the "ring-vacuolate stage" with a collapsed morphology without the typical exine patterns, pointing to a sporophytic defect. These microspores were unviable and therefore never germinated in vitro. L. ovalifolium individuals presented larger pollen grains than those of L. multiflorum, indicating that pollen size and ploidy levels are not correlated in the Limonium system. Cytohistological studies in mature seeds from both species revealed that an embryo and a residual endosperm were present in each seed. Flow cytometric seed screens using such mature seeds showed quantitative variations in seeds ploidy level. It is concluded that male function seems to play an important role in the reproduction modes of Limonium diploids and tetraploids. PMID:23086613

  20. Quantitative PCR reveals strong spatial and temporal variation of the wasting disease pathogen, Labyrinthula zosterae in northern European eelgrass (Zostera marina) beds.

    PubMed

    Bockelmann, Anna-Christina; Tams, Verena; Ploog, Jana; Schubert, Philipp R; Reusch, Thorsten B H

    2013-01-01

    Seagrass beds are the foundation species of functionally important coastal ecosystems worldwide. The world's largest losses of the widespread seagrass Zostera marina (eelgrass) have been reported as a consequence of wasting disease, an infection with the endophytic protist Labyrinthula zosterae. During one of the most extended epidemics in the marine realm, ?90% of East and Western Atlantic eelgrass beds died-off between 1932 and 1934. Today, small outbreaks continue to be reported, but the current extent of L. zosterae in European meadows is completely unknown. In this study we quantify the abundance and prevalence of the wasting disease pathogen among 19 Z. marina populations in northern European coastal waters, using quantitative PCR (QPCR) with primers targeting a species specific portion of the internally transcribed spacer (ITS1) of L. zosterae. Spatially, we found marked variation among sites with abundances varying between 0 and 126 cells mg(-1) Z. marina dry weight (mean: 5.7 L. zosterae cells mg(-1) Z. marina dry weight ±1.9 SE) and prevalences ranged from 0-88.9%. Temporarily, abundances varied between 0 and 271 cells mg(-1) Z. marina dry weight (mean: 8.5±2.6 SE), while prevalences ranged from zero in winter and early spring to 96% in summer. Field concentrations accessed via bulk DNA extraction and subsequent QPCR correlated well with prevalence data estimated via isolation and cultivation from live plant tissue. L. zosterae was not only detectable in black lesions, a sign of Labyrinthula-induced necrosis, but also occurred in green, apparently healthy tissue. We conclude that L. zosterae infection is common (84% infected populations) in (northern) European eelgrass populations with highest abundances during the summer months. In the light of global climate change and increasing rate of marine diseases our data provide a baseline for further studies on the causes of pathogenic outbreaks of L. zosterae. PMID:23658711

  1. Hairy?s Inheritance: Investigating Variation, Selection, and Evolution with Wisconsin Fast Plants

    NSDL National Science Digital Library

    Lauffer, Daniel W.

    In this investigation, learners will gather their own evidence to explain how environmental pressures (selection for hairiness) and inheritance can effect phenotypic variation over time. As learners observe two or more generations of Wisconsin Fast Plants, learners observe carefully and track quantitatively the average number of hairs on the first true leaf margin of Rapid-cycling Brassica rapa (Fast Plants). As the generations of plants grow, students will make observations that will serve as evidence to support or refute their explanations about the observed patterns in the inheritance of the hairy trait.-This pdf file contains considerable background information about Brassicas and the relationship among phenotype, genotype, and environment.

  2. Propagation of genetic variation in gene regulatory networks

    NASA Astrophysics Data System (ADS)

    Plahte, Erik; Gjuvsland, Arne B.; Omholt, Stig W.

    2013-08-01

    A future quantitative genetics theory should link genetic variation to phenotypic variation in a causally cohesive way based on how genes actually work and interact. We provide a theoretical framework for predicting and understanding the manifestation of genetic variation in haploid and diploid regulatory networks with arbitrary feedback structures and intra-locus and inter-locus functional dependencies. Using results from network and graph theory, we define propagation functions describing how genetic variation in a locus is propagated through the network, and show how their derivatives are related to the network’s feedback structure. Similarly, feedback functions describe the effect of genotypic variation of a locus on itself, either directly or mediated by the network. A simple sign rule relates the sign of the derivative of the feedback function of any locus to the feedback loops involving that particular locus. We show that the sign of the phenotypically manifested interaction between alleles at a diploid locus is equal to the sign of the dominant feedback loop involving that particular locus, in accordance with recent results for a single locus system. Our results provide tools by which one can use observable equilibrium concentrations of gene products to disclose structural properties of the network architecture. Our work is a step towards a theory capable of explaining the pleiotropy and epistasis features of genetic variation in complex regulatory networks as functions of regulatory anatomy and functional location of the genetic variation.

  3. Mapping quantitative trait loci controlling seed dormancy and heading date in rice, Oryza sativa L., using backcross inbred lines

    Microsoft Academic Search

    S. Y. Lin; T. Sasaki; M. Yano

    1998-01-01

    To detect quantitative trait loci (QTLs) controlling seed dormancy, 98 BC1F5 lines (backcross inbred lines) derived from a backcross of Nipponbare (japonica)\\/Kasalath (indica)\\/\\/Nipponbare were analyzed genetically. We used 245 RFLP markers to construct a framework linkage map. Five putative QTLs\\u000a affecting seed dormancy were detected on chromosomes 3, 5, 7 (two regions) and 8, respectively. Phenotypic variations explained\\u000a by each

  4. Integrating Quantitative Knowledge into a Qualitative Gene Regulatory Network

    PubMed Central

    Bourdon, Jérémie; Eveillard, Damien; Siegel, Anne

    2011-01-01

    Despite recent improvements in molecular techniques, biological knowledge remains incomplete. Any theorizing about living systems is therefore necessarily based on the use of heterogeneous and partial information. Much current research has focused successfully on the qualitative behaviors of macromolecular networks. Nonetheless, it is not capable of taking into account available quantitative information such as time-series protein concentration variations. The present work proposes a probabilistic modeling framework that integrates both kinds of information. Average case analysis methods are used in combination with Markov chains to link qualitative information about transcriptional regulations to quantitative information about protein concentrations. The approach is illustrated by modeling the carbon starvation response in Escherichia coli. It accurately predicts the quantitative time-series evolution of several protein concentrations using only knowledge of discrete gene interactions and a small number of quantitative observations on a single protein concentration. From this, the modeling technique also derives a ranking of interactions with respect to their importance during the experiment considered. Such a classification is confirmed by the literature. Therefore, our method is principally novel in that it allows (i) a hybrid model that integrates both qualitative discrete model and quantities to be built, even using a small amount of quantitative information, (ii) new quantitative predictions to be derived, (iii) the robustness and relevance of interactions with respect to phenotypic criteria to be precisely quantified, and (iv) the key features of the model to be extracted that can be used as a guidance to design future experiments. PMID:21935350

  5. Statistical models for trisomic phenotypes

    SciTech Connect

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  6. Genome-wide nested association mapping of quantitative resistance to northern leaf blight in maize

    PubMed Central

    Poland, Jesse A.; Bradbury, Peter J.; Buckler, Edward S.; Nelson, Rebecca J.

    2011-01-01

    Quantitative resistance to plant pathogens, controlled by multiple loci of small effect, is important for food production, food security, and food safety but is poorly understood. To gain insights into the genetic architecture of quantitative resistance in maize, we evaluated a 5,000-inbred-line nested association mapping population for resistance to northern leaf blight, a maize disease of global economic importance. Twenty-nine quantitative trait loci were identified, and most had multiple alleles. The large variation in resistance phenotypes could be attributed to the accumulation of numerous loci of small additive effects. Genome-wide nested association mapping, using 1.6 million SNPs, identified multiple candidate genes related to plant defense, including receptor-like kinase genes similar to those involved in basal defense. These results are consistent with the hypothesis that quantitative disease resistance in plants is conditioned by a range of mechanisms and could have considerable mechanistic overlap with basal resistance. PMID:21482771

  7. Dominance genetic variation contributes little to the missing heritability for human complex traits.

    PubMed

    Zhu, Zhihong; Bakshi, Andrew; Vinkhuyzen, Anna A E; Hemani, Gibran; Lee, Sang Hong; Nolte, Ilja M; van Vliet-Ostaptchouk, Jana V; Snieder, Harold; Esko, Tonu; Milani, Lili; Mägi, Reedik; Metspalu, Andres; Hill, William G; Weir, Bruce S; Goddard, Michael E; Visscher, Peter M; Yang, Jian

    2015-03-01

    For human complex traits, non-additive genetic variation has been invoked to explain "missing heritability," but its discovery is often neglected in genome-wide association studies. Here we propose a method of using SNP data to partition and estimate the proportion of phenotypic variance attributed to additive and dominance genetic variation at all SNPs (hSNP(2) and ?SNP(2)) in unrelated individuals based on an orthogonal model where the estimate of hSNP(2) is independent of that of ?SNP(2). With this method, we analyzed 79 quantitative traits in 6,715 unrelated European Americans. The estimate of ?SNP(2) averaged across all the 79 quantitative traits was 0.03, approximately a fifth of that for additive variation (average hSNP(2) = 0.15). There were a few traits that showed substantial estimates of ?SNP(2), none of which were replicated in a larger sample of 11,965 individuals. We further performed genome-wide association analyses of the 79 quantitative traits and detected SNPs with genome-wide significant dominance effects only at the ABO locus for factor VIII and von Willebrand factor. All these results suggest that dominance variation at common SNPs explains only a small fraction of phenotypic variation for human complex traits and contributes little to the missing narrow-sense heritability problem. PMID:25683123

  8. First insights into the genotype–phenotype map of phenotypic stability in rye

    PubMed Central

    Wang, Yu; Mette, Michael Florian; Miedaner, Thomas; Wilde, Peer; Reif, Jochen C.; Zhao, Yusheng

    2015-01-01

    Improving phenotypic stability of crops is pivotal for coping with the detrimental impacts of climate change. The goal of this study was to gain first insights into the genetic architecture of phenotypic stability in cereals. To this end, we determined grain yield, thousand kernel weight, test weight, falling number, and both protein and soluble pentosan content for two large bi-parental rye populations connected through one common parent and grown in multi-environmental field trials involving more than 15 000 yield plots. Based on these extensive phenotypic data, we calculated parameters for static and dynamic phenotypic stability of the different traits and applied linkage mapping using whole-genome molecular marker profiles. While we observed an absence of large-effect quantitative trait loci (QTLs) underlying yield stability, large and stable QTLs were found for phenotypic stability of test weight, soluble pentosan content, and falling number. Applying genome-wide selection, which in contrast to marker-assisted selection also takes into account loci with small-effect sizes, considerably increased the accuracy of prediction of phenotypic stability for all traits by exploiting both genetic relatedness and linkage between single-nucleotide polymorphisms and QTLs. We conclude that breeding for crop phenotypic stability can be improved in related populations using genomic selection approaches established upon extensive phenotypic data. PMID:25873667

  9. First insights into the genotype-phenotype map of phenotypic stability in rye.

    PubMed

    Wang, Yu; Mette, Michael Florian; Miedaner, Thomas; Wilde, Peer; Reif, Jochen C; Zhao, Yusheng

    2015-06-01

    Improving phenotypic stability of crops is pivotal for coping with the detrimental impacts of climate change. The goal of this study was to gain first insights into the genetic architecture of phenotypic stability in cereals. To this end, we determined grain yield, thousand kernel weight, test weight, falling number, and both protein and soluble pentosan content for two large bi-parental rye populations connected through one common parent and grown in multi-environmental field trials involving more than 15 000 yield plots. Based on these extensive phenotypic data, we calculated parameters for static and dynamic phenotypic stability of the different traits and applied linkage mapping using whole-genome molecular marker profiles. While we observed an absence of large-effect quantitative trait loci (QTLs) underlying yield stability, large and stable QTLs were found for phenotypic stability of test weight, soluble pentosan content, and falling number. Applying genome-wide selection, which in contrast to marker-assisted selection also takes into account loci with small-effect sizes, considerably increased the accuracy of prediction of phenotypic stability for all traits by exploiting both genetic relatedness and linkage between single-nucleotide polymorphisms and QTLs. We conclude that breeding for crop phenotypic stability can be improved in related populations using genomic selection approaches established upon extensive phenotypic data. PMID:25873667

  10. Classification of cassava genotypes based on qualitative and quantitative data.

    PubMed

    Oliveira, E J; Oliveira Filho, O S; Santos, V S

    2015-01-01

    We evaluated the genetic variation of cassava accessions based on qualitative (binomial and multicategorical) and quantitative traits (continuous). We characterized 95 accessions obtained from the Cassava Germplasm Bank of Embrapa Mandioca e Fruticultura; we evaluated these accessions for 13 continuous, 10 binary, and 25 multicategorical traits. First, we analyzed the accessions based only on quantitative traits; next, we conducted joint analysis (qualitative and quantitative traits) based on the Ward-MLM method, which performs clustering in two stages. According to the pseudo-F, pseudo-t2, and maximum likelihood criteria, we identified five and four groups based on quantitative trait and joint analysis, respectively. The smaller number of groups identified based on joint analysis may be related to the nature of the data. On the other hand, quantitative data are more subject to environmental effects in the phenotype expression; this results in the absence of genetic differences, thereby contributing to greater differentiation among accessions. For most of the accessions, the maximum probability of classification was >0.90, independent of the trait analyzed, indicating a good fit of the clustering method. Differences in clustering according to the type of data implied that analysis of quantitative and qualitative traits in cassava germplasm might explore different genomic regions. On the other hand, when joint analysis was used, the means and ranges of genetic distances were high, indicating that the Ward-MLM method is very useful for clustering genotypes when there are several phenotypic traits, such as in the case of genetic resources and breeding programs. PMID:25730029

  11. A Review of Imaging Techniques for Plant Phenotyping

    PubMed Central

    Li, Lei; Zhang, Qin; Huang, Danfeng

    2014-01-01

    Given the rapid development of plant genomic technologies, a lack of access to plant phenotyping capabilities limits our ability to dissect the genetics of quantitative traits. Effective, high-throughput phenotyping platforms have recently been developed to solve this problem. In high-throughput phenotyping platforms, a variety of imaging methodologies are being used to collect data for quantitative studies of complex traits related to the growth, yield and adaptation to biotic or abiotic stress (disease, insects, drought and salinity). These imaging techniques include visible imaging (machine vision), imaging spectroscopy (multispectral and hyperspectral remote sensing), thermal infrared imaging, fluorescence imaging, 3D imaging and tomographic imaging (MRT, PET and CT). This paper presents a brief review on these imaging techniques and their applications in plant phenotyping. The features used to apply these imaging techniques to plant phenotyping are described and discussed in this review. PMID:25347588

  12. A review of imaging techniques for plant phenotyping.

    PubMed

    Li, Lei; Zhang, Qin; Huang, Danfeng

    2014-01-01

    Given the rapid development of plant genomic technologies, a lack of access to plant phenotyping capabilities limits our ability to dissect the genetics of quantitative traits. Effective, high-throughput phenotyping platforms have recently been developed to solve this problem. In high-throughput phenotyping platforms, a variety of imaging methodologies are being used to collect data for quantitative studies of complex traits related to the growth, yield and adaptation to biotic or abiotic stress (disease, insects, drought and salinity). These imaging techniques include visible imaging (machine vision), imaging spectroscopy (multispectral and hyperspectral remote sensing), thermal infrared imaging, fluorescence imaging, 3D imaging and tomographic imaging (MRT, PET and CT). This paper presents a brief review on these imaging techniques and their applications in plant phenotyping. The features used to apply these imaging techniques to plant phenotyping are described and discussed in this review. PMID:25347588

  13. [Research progress on the phenotype informative SNP in forensic science].

    PubMed

    Liu, Yu-Xuan; Hu, Qing-Qing; Ma, Hong-Du; Huang, Dai-Xin

    2014-10-01

    Single nucleotide polymorphism (SNP) refers to the single base sequence variation in specific location of the human genome. Phenotype informative SNP has gradually become one of the research hot spots in forensic science. In this paper, the forensic research situation and application prospect of phenotype informative SNP in the characteristics of hair, eye and skin color, height, and facial feature are reviewed. PMID:25735077

  14. Factors That Contribute to Assay Variation in Quantitative Analysis of Sex Steroid Hormones Using Liquid and Gas Chromatography-Mass Spectrometry

    ERIC Educational Resources Information Center

    Xu, Xia; Veenstra, Timothy D.

    2012-01-01

    The list of physiological events in which sex steroids play a role continues to increase. To decipher the roles that sex steroids play in any condition requires high quality cohorts of samples and assays that provide highly accurate quantitative measures. Liquid and gas chromatography coupled with mass spectrometry (LC-MS and GC-MS) have…

  15. Wine Expertise Predicts Taste Phenotype

    PubMed Central

    Hayes, John E; Pickering, Gary J

    2011-01-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance – with appropriate caveats about populations tested, outcomes measured and psychophysical methods used – an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli. PMID:22888174

  16. Phenotypic and genomic plasticity of alternative male reproductive tactics in sailfin mollies

    PubMed Central

    Fraser, Bonnie A.; Janowitz, Ilana; Thairu, Margaret; Travis, Joseph; Hughes, Kimberly A.

    2014-01-01

    A major goal of modern evolutionary biology is to understand the causes and consequences of phenotypic plasticity, the ability of a single genotype to produce multiple phenotypes in response to variable environments. While ecological and quantitative genetic studies have evaluated models of the evolution of adaptive plasticity, some long-standing questions about plasticity require more mechanistic approaches. Here, we address two of those questions: does plasticity facilitate adaptive evolution? And do physiological costs place limits on plasticity? We examine these questions by comparing genetically and plastically regulated behavioural variation in sailfin mollies (Poecilia latipinna), which exhibit striking variation in plasticity for male mating behaviour. In this species, some genotypes respond plastically to a change in the social environment by switching between primarily courting and primarily sneaking behaviour. In contrast, other genotypes have fixed mating strategies (either courting or sneaking) and do not display plasticity. We found that genetic and plastic variation in behaviour were accompanied by partially, but not completely overlapping changes in brain gene expression, in partial support of models that predict that plasticity can facilitate adaptive evolution. We also found that behavioural plasticity was accompanied by broader and more robust changes in brain gene expression, suggesting a substantial physiological cost to plasticity. We also observed that sneaking behaviour, but not courting, was associated with upregulation of genes involved in learning and memory, suggesting that sneaking is more cognitively demanding than courtship. PMID:24573842

  17. A New Method to Infer Causal Phenotype Networks Using QTL and Phenotypic Information

    PubMed Central

    Wang, Huange; van Eeuwijk, Fred A.

    2014-01-01

    In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at quantitative trait loci (QTLs) to learn about causal relationships among phenotypic traits. A requirement for using these approaches is that at least one unique QTL has been identified for each trait studied. However, in practice, especially for molecular phenotypes such as metabolites, this prerequisite is often not met due to limited sample sizes, high noise levels and small QTL effects. Here, we present a novel heuristic search algorithm called the QTL+phenotype supervised orientation (QPSO) algorithm to infer causal directions for edges in undirected phenotype networks. The two main advantages of this algorithm are: first, it does not require QTLs for each and every trait; second, it takes into account associated phenotypic interactions in addition to detected QTLs when orienting undirected edges between traits. We evaluate and compare the performance of QPSO with another state-of-the-art approach, the QTL-directed dependency graph (QDG) algorithm. Simulation results show that our method has broader applicability and leads to more accurate overall orientations. We also illustrate our method with a real-life example involving 24 metabolites and a few major QTLs measured on an association panel of 93 tomato cultivars. Matlab source code implementing the proposed algorithm is freely available upon request. PMID:25144184

  18. Enabling Population and Quantitative Genomics

    Microsoft Academic Search

    GREG GIBSON; TRUDY F. C. MACKAY

    2002-01-01

    Summary Dissection of quantitative traits to the nucleotide level requires phenotypic and genotypic analysis of traits on a genome scale. Here we discuss the set of community-wide genetic and molecular resources, including panels of specific types of inbred lines and high density resequencing and SNP detection, that will facilitate such studies. 1. Background

  19. Quantitative genomics of female reproduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous quantitative trait loci (QTL) for reproductive traits in domestic livestock have been described in the literature. In this chapter, the components needed for detection of reproductive trait QTL are described, including collection of phenotypes, genotypes, and the appropriate statistical ana...

  20. Short communication: Genome-wide scan for bovine milk-fat composition. II. Quantitative trait loci for long-chain fatty acids

    Microsoft Academic Search

    A. Schennink; W. M. Stoop; M. H. P. W. Visker; J. J. van der Poel; H. Bovenhuis; Arendonk van J. A. M

    2009-01-01

    We present the results of a genome-wide scan to identify quantitative trait loci (QTL) that contribute to genetic variation in long-chain milk fatty acids. Milk-fat composition phenotypes were available on 1,905 Dutch Holstein-Friesian cows. A total of 849 cows and their 7 sires were genotyped for 1,341 single nucleotide polymorphisms across all Bos taurus autosomes (BTA). We detected significant QTL

  1. Sex differences in grey seal diet reflect seasonal variation in foraging behaviour and reproductive expenditure: evidence from quantitative fatty acid signature analysis

    Microsoft Academic Search

    CARRIE A. BECK; SARA J. IVERSON; W. DON BOWEN; WADE BLANCHARD

    2007-01-01

    Summary 1. Intraspecific variation in diet can be an important component of a species niche breadth. We tested the hypothesis that sex differences in seasonal foraging behaviour and energy storage of sexually size dimorphic grey seals Halichoerus grypus (Fabrisius 1971) are reflected in differences in the diet and niche breadth. Diet composition was estimated for 496 adult (226 males, 270

  2. Flavonoid sequestration by the common blue butterfly Polyommatus icarus: quantitative intraspecific variation in relation to larval hostplant, sex and body size

    Microsoft Academic Search

    Frank Burghardt; Peter Proksch; Konrad Fiedler

    2001-01-01

    Common blue butterflies (Polyommatus icarus) sequester flavonoids from their larval food and store these pigments as part of their adult wing colouration. Insects were reared on 10 different diets to assess effects of host plants on variation in flavonoid sequestration in this moderately polyphagous butterfly. Rearing experiments revealed an unexpectedly large gradient in flavonoid richness, ranging from individuals with high

  3. Integrating Genetic and Environmental Forces that Shape the Evolution of Geographic Variation in a Marine Snail

    Microsoft Academic Search

    Geoffrey C. Trussell; Ron J. Etter

    Temporal and spatial patterns of phenotypic variation have traditionally been thought to reflect genetic differentiation produced by natural selection. Recently, however, there has been growing interest in how natural selection may shape the genetics of phenotypic plasticity to produce patterns of geographic variation and phenotypic evolution. Because the covariance between genetic and environmental influences can modulate the expression of phenotypic

  4. The Drosophila phenotype ontology

    PubMed Central

    2013-01-01

    Background Phenotype ontologies are queryable classifications of phenotypes. They provide a widely-used means for annotating phenotypes in a form that is human-readable, programatically accessible and that can be used to group annotations in biologically meaningful ways. Accurate manual annotation requires clear textual definitions for terms. Accurate grouping and fruitful programatic usage require high-quality formal definitions that can be used to automate classification. The Drosophila?phenotype ontology (DPO) has been used to annotate over 159,000 phenotypes in FlyBase to date, but until recently lacked textual or formal definitions. Results We have composed textual definitions for all DPO terms and formal definitions for 77% of them. Formal definitions reference terms from a range of widely-used ontologies including the Phenotype and Trait Ontology (PATO), the Gene Ontology (GO) and the Cell Ontology (CL). We also describe a generally applicable system, devised for the DPO, for recording and reasoning about the timing of death in populations. As a result of the new formalisations, 85% of classifications in the DPO are now inferred rather than asserted, with much of this classification leveraging the structure of the GO. This work has significantly improved the accuracy and completeness of classification and made further development of the DPO more sustainable. Conclusions The DPO provides a set of well-defined terms for annotating Drosophila?phenotypes and for grouping and querying the resulting annotation sets in biologically meaningful ways. Such queries have already resulted in successful function predictions from phenotype annotation. Moreover, such formalisations make extended queries possible, including cross-species queries via the external ontologies used in formal definitions. The DPO is openly available under an open source license in both OBO and OWL formats. There is good potential for it to be used more broadly by the Drosophila?community, which may ultimately result in its extension to cover a broader range of phenotypes. PMID:24138933

  5. Imaging and Analysis Platform for Automatic Phenotyping and Trait Ranking of Plant Root Systems1[W][OA

    PubMed Central

    Iyer-Pascuzzi, Anjali S.; Symonova, Olga; Mileyko, Yuriy; Hao, Yueling; Belcher, Heather; Harer, John; Weitz, Joshua S.; Benfey, Philip N.

    2010-01-01

    The ability to nondestructively image and automatically phenotype complex root systems, like those of rice (Oryza sativa), is fundamental to identifying genes underlying root system architecture (RSA). Although root systems are central to plant fitness, identifying genes responsible for RSA remains an underexplored opportunity for crop improvement. Here we describe a nondestructive imaging and analysis system for automated phenotyping and trait ranking of RSA. Using this system, we image rice roots from 12 genotypes. We automatically estimate RSA traits previously identified as important to plant function. In addition, we expand the suite of features examined for RSA to include traits that more comprehensively describe monocot RSA but that are difficult to measure with traditional methods. Using 16 automatically acquired phenotypic traits for 2,297 images from 118 individuals, we observe (1) wide variation in phenotypes among the genotypes surveyed; and (2) greater intergenotype variance of RSA features than variance within a genotype. RSA trait values are integrated into a computational pipeline that utilizes supervised learning methods to determine which traits best separate two genotypes, and then ranks the traits according to their contribution to each pairwise comparison. This trait-ranking step identifies candidate traits for subsequent quantitative trait loci analysis and demonstrates that depth and average radius are key contributors to differences in rice RSA within our set of genotypes. Our results suggest a strong genetic component underlying rice RSA. This work enables the automatic phenotyping of RSA of individuals within mapping populations, providing an integrative framework for quantitative trait loci analysis of RSA. PMID:20107024

  6. Developmental trajectories as autism phenotypes.

    PubMed

    Lord, Catherine; Bishop, Somer; Anderson, Deborah

    2015-06-01

    Numerous studies of Autism Spectrum Disorder have attempted to link behavioral phenotypes to genetic findings. Reliance on cross-sectional behavioral data in samples that span wide age ranges may have limited this endeavor because ASD behaviors are not static within individuals across development. This study uses quantitative methods to describe specific aspects of changes in autism-related and more general behaviors in order to yield trajectories that could be used in place of single time-point data as behavioral phenotypes in neurobiological studies of both Autism Spectrum Disorders and overlapping conditions. Building on previous analyses, we examined trajectories of parent-reported social-communication deficits, social adaptive functioning, and two types of repetitive behaviors, repetitive sensory motor (RSM) behaviors and insistence on sameness (IS) behaviors, in a relatively large sample of participants referred for possible autism at age 2 years and followed into young adulthood (n?=?85). A strength of this sample was the diverse range of outcomes, including young adults with intellectual disability and persistent autism related difficulties, those with IQs in the borderline or average range who continued to experience functional impairment related to Autism Spectrum Disorders, and a small group of young adults (n?=?8) with IQs in the average range who were judged to be functioning socially and adaptively at age-appropriate levels at age 19 years, despite a previous childhood diagnosis of autism. PMID:25959391

  7. Three monthly coral Sr/Ca records from the Chagos Archipelago covering the period of 1950-1995 A.D.: reproducibility and implications for quantitative reconstructions of sea surface temperature variations

    NASA Astrophysics Data System (ADS)

    Pfeiffer, Miriam; Dullo, Wolf-Christian; Zinke, Jens; Garbe-Schönberg, Dieter

    2009-02-01

    In order to assess the fidelity of coral Sr/Ca for quantitative reconstructions of sea surface temperature variations, we have generated three monthly Sr/Ca time series from Porites corals from the lagoon of Peros Banhos (71°E, 5°S, Chagos Archipelago). We find that all three coral Sr/Ca time series are well correlated with instrumental records of sea surface temperature (SST) and air temperature. However, the intrinsic variance of the single-core Sr/Ca time series differs from core to core, limiting their use for quantitative estimates of past temperature variations. Averaging the single-core data improves the correlation with instrumental temperature ( r > 0.7) and allows accurate estimates of interannual temperature variations (~0.35°C or better). All Sr/Ca time series indicate a shift towards warmer temperatures in the mid-1970s, which coincides with the most recent regime shift in the Pacific Ocean. However, the magnitude of the warming inferred from coral Sr/Ca differs from core to core and ranges from 0.26 to 0.75°C. The composite Sr/Ca record from Peros Banhos clearly captures the major climatic signals in the Indo-Pacific Ocean, i.e. the El Niño-southern oscillation and the Pacific decadal oscillation. Moreover, composite Sr/Ca is highly correlated with tropical mean temperatures ( r = 0.7), suggesting that coral Sr/Ca time series from the tropical Indian Ocean will contribute to multi-proxy reconstructions of tropical mean temperatures.

  8. The Evolutionary Genetics of the Genes Underlying Phenotypic Associations for Loblolly Pine (Pinus taeda, Pinaceae)

    PubMed Central

    Eckert, Andrew J.; Wegrzyn, Jill L.; Liechty, John D.; Lee, Jennifer M.; Cumbie, W. Patrick; Davis, John M.; Goldfarb, Barry; Loopstra, Carol A.; Palle, Sreenath R.; Quesada, Tania; Langley, Charles H.; Neale, David B.

    2013-01-01

    A primary goal of evolutionary genetics is to discover and explain the genetic basis of fitness-related traits and how this genetic basis evolves within natural populations. Unprecedented technological advances have fueled the discovery of genetic variants associated with ecologically relevant phenotypes in many different life forms, as well as the ability to scan genomes for deviations from selectively neutral models of evolution. Theoretically, the degree of overlap between lists of genomic regions identified using each approach is related to the genetic architecture of fitness-related traits and the strength and type of natural selection molding variation at these traits within natural populations. Here we address for the first time in a plant the degree of overlap between these lists, using patterns of nucleotide diversity and divergence for >7000 unique amplicons described from the extensive expressed sequence tag libraries generated for loblolly pine (Pinus taeda L.) in combination with the >1000 published genetic associations. We show that loci associated with phenotypic traits are distinct with regard to neutral expectations. Phenotypes measured at the whole plant level (e.g., disease resistance) exhibit an approximately twofold increase in the proportion of adaptive nonsynonymous substitutions over the genome-wide average. As expected for polygenic traits, these signals were apparent only when loci were considered at the level of functional sets. The ramifications of this result are discussed in light of the continued efforts to dissect the genetic basis of quantitative traits. PMID:24121773

  9. Quantitative Assessment of Intra-Patient Variation in CD4+ T Cell Counts in Stable, Virologically-Suppressed, HIV-Infected Subjects

    PubMed Central

    Gordon, Claire L.; Cheng, Allen C.; Cameron, Paul U.; Bailey, Michael; Crowe, Suzanne M.; Mills, John

    2015-01-01

    Objectives Counts of absolute CD4+ T lymphocytes (CD4+ T cells) are known to be highly variable in untreated HIV-infected individuals, but there are no data in virologically-suppressed individuals. We investigated CD4+ T cell variability in stable, virologically-suppressed, HIV-1 infected adults on combination antiretroviral therapy (cART). Methods From a large hospital database we selected patients with stable virological suppression on cART for >3 years with >10 CD4+ T cell measurements performed over a further >2 years; and a control group of 95 patients not on cART. Results We identified 161 HIV-infected patients on cART without active HCV or HBV infection, with stable virological suppression for a median of 6.4 years. Over the study period 88 patients had reached a plateau in their absolute CD4+ T cell counts, while 65 patients had increasing and 8 patients had decreasing absolute CD4+ T cell counts. In patients with plateaued CD4+ T cell counts, variability in absolute CD4+ T cell counts was greater than in percent CD4+ T cells (median coefficient of variation (CV) 16.6% [IQR 13.8-20.1%] and CV 9.6% [IQR 7.4-13.0%], respectively). Patients with increasing CD4+ T cell counts had greater variability in absolute CD4+ T cell counts than those with plateaued CD4 T cell counts (CV 19.5% [IQR 16.1-23.8%], p<0.001) while there was no difference in percent CD4+ T cell variability between the two groups. As previously reported, untreated patients had CVs significantly higher than patients on cART (CVs of 21.1% [IQR 17.2-32.0%], p<0.001 and 15.2% (IQR 10.7-20.0%), p<0.001, respectively). Age or sex did not affect the degree of CD4+ variation. Conclusions Adults with stable, virologically-suppressed HIV infection continue to have significant variations in individual absolute CD4+ T cell and percent CD4+ T cell counts; this variation can be of clinical relevance especially around CD4+ thresholds. However, the variation seen in individuals on cART is substantially less than in untreated subjects. PMID:26110761

  10. Integrative Genomics: Quantifying Significance of Phenotype-Genotype Relationships from Multiple Sources of High-Throughput Data

    PubMed Central

    Gamazon, Eric R.; Huang, R. Stephanie; Dolan, M. Eileen; Cox, Nancy J.; Im, Hae Kyung

    2013-01-01

    Given recent advances in the generation of high-throughput data such as whole-genome genetic variation and transcriptome expression, it is critical to come up with novel methods to integrate these heterogeneous datasets and to assess the significance of identified phenotype-genotype relationships. Recent studies show that genome-wide association findings are likely to fall in loci with gene regulatory effects such as expression quantitative trait loci (eQTLs), demonstrating the utility of such integrative approaches. When genotype and gene expression data are available on the same individuals, we and others developed methods wherein top phenotype-associated genetic variants are prioritized if they are associated, as eQTLs, with gene expression traits that are themselves associated with the phenotype. Yet there has been no method to determine an overall p-value for the findings that arise specifically from the integrative nature of the approach. We propose a computationally feasible permutation method that accounts for the assimilative nature of the method and the correlation structure among gene expression traits and among genotypes. We apply the method to data from a study of cellular sensitivity to etoposide, one of the most widely used chemotherapeutic drugs. To our knowledge, this study is the first statistically sound quantification of the overall significance of the genotype-phenotype relationships resulting from applying an integrative approach. This method can be easily extended to cases in which gene expression data are replaced by other molecular phenotypes of interest, e.g., microRNA or proteomic data. This study has important implications for studies seeking to expand on genetic association studies by the use of omics data. Finally, we provide an R code to compute the empirical false discovery rate when p-values for the observed and simulated phenotypes are available. PMID:23755062

  11. High-Resolution Inflorescence Phenotyping Using a Novel Image-Analysis Pipeline, PANorama1[W][OPEN

    PubMed Central

    Crowell, Samuel; Falcão, Alexandre X.; Shah, Ankur; Wilson, Zachary; Greenberg, Anthony J.; McCouch, Susan R.

    2014-01-01

    Variation in inflorescence development is an important target of selection for numerous crop species, including many members of the Poaceae (grasses). In Asian rice (Oryza sativa), inflorescence (panicle) architecture is correlated with yield and grain-quality traits. However, many rice breeders continue to use composite phenotypes in selection pipelines, because measuring complex, branched panicles requires a significant investment of resources. We developed an open-source phenotyping platform, PANorama, which measures multiple architectural and branching phenotypes from images simultaneously. PANorama automatically extracts skeletons from images, allows users to subdivide axes into individual internodes, and thresholds away structures, such as awns, that normally interfere with accurate panicle phenotyping. PANorama represents an improvement in both efficiency and accuracy over existing panicle imaging platforms, and flexible implementation makes PANorama capable of measuring a range of organs from other plant species. Using high-resolution phenotypes, a mapping population of recombinant inbred lines, and a dense single-nucleotide polymorphism data set, we identify, to our knowledge, the largest number of quantitative trait loci (QTLs) for panicle traits ever reported in a single study. Several areas of the genome show pleiotropic clusters of panicle QTLs, including a region near the rice Green Revolution gene SEMIDWARF1. We also confirm that multiple panicle phenotypes are distinctly different among a small collection of diverse rice varieties. Taken together, these results suggest that clusters of small-effect QTLs may be responsible for varietal or subpopulation-specific panicle traits, representing a significant opportunity for rice breeders selecting for yield performance across different genetic backgrounds. PMID:24696519

  12. Cross-cultural variation in blood pressure: a quantitative analysis of the relationships of blood pressure to cultural characteristics, salt consumption and body weight.

    PubMed

    Waldron, I; Nowotarski, M; Freimer, M; Henry, J P; Post, N; Witten, C

    1982-01-01

    This study has analyzed the relationships of cross-cultural variation in blood pressure to cultural characteristics, salt consumption and body weight. The data used were blood pressures for adults in 84 groups, ratings of cultural characteristics (based on anthropological data and made by raters who had no knowledge of the blood pressure data) and, where available, salt consumption and body mass index (weight/height2). Blood pressures were higher and the slopes of blood pressure with age were greater in groups which had greater involvement in a money economy, more economic competition, more contact with people of different culture or beliefs, and more unfulfilled aspirations for a return to traditional beliefs and values. Blood pressures were also higher in groups for which the predominant family type was a nuclear or father-absent family, as opposed to an extended family. For Negroes, groups who were descended from slaves had higher blood pressures than other groups. The correlations between blood pressures and involvement in a money economy were substantial and significant even after controlling for level of salt consumption and, for men, also after controlling for body mass index. For men there were also significant partial correlations between blood pressure and salt consumption, controlling for type of economy. For women there were significant partial correlations between blood pressure and body mass index, controlling for type of economy. In conclusion, cross-cultural variation in blood pressure appears to be due to multiple factors. One contributory factor appears to be psychosocial stress due to cultural disruption, including the disruption of cooperative relationships and traditional cultural patterns which frequently occurs during economic modernization. In addition, both the protective effects of very low salt consumption in some groups and differences in body weight appear to contribute to cross-cultural variation in blood pressure. PMID:7079796

  13. Heritable Variation in Garter Snake Color Patterns in Postglacial Populations

    PubMed Central

    Westphal, Michael F.; Massie, Jodi L.; Bronkema, Joanna M.; Smith, Brian E.; Morgan, Theodore J.

    2011-01-01

    Global climate change is expected to trigger northward shifts in the ranges of natural populations of plants and animals, with subsequent effects on intraspecific genetic diversity. Investigating how genetic diversity is patterned among populations that arose following the last Ice Age is a promising method for understanding the potential future effects of climate change. Theoretical and empirical work has suggested that overall genetic diversity can decrease in colonial populations following rapid expansion into postglacial landscapes, with potential negative effects on the ability of populations to adapt to new environmental regimes. The crucial measure of this genetic variation and a population's overall adaptability is the heritable variation in phenotypic traits, as it is this variation that mediates the rate and direction of a population's multigenerational response to selection. Using two large full-sib quantitative genetic studies (NManitoba?=?144; NSouth Dakota?=?653) and a smaller phenotypic analysis from Kansas (NKansas?=?44), we compared mean levels of pigmentation, genetic variation and heritability in three pigmentation traits among populations of the common garter snake, Thamnophis sirtalis, along a north-south gradient, including a postglacial northern population and a putative southern refuge population. Counter to our expectations, we found that genetic variance and heritability for the three pigmentation traits were the same or higher in the postglacial population than in the southern population. PMID:21935386

  14. Heritable variation in garter snake color patterns in postglacial populations.

    PubMed

    Westphal, Michael F; Massie, Jodi L; Bronkema, Joanna M; Smith, Brian E; Morgan, Theodore J

    2011-01-01

    Global climate change is expected to trigger northward shifts in the ranges of natural populations of plants and animals, with subsequent effects on intraspecific genetic diversity. Investigating how genetic diversity is patterned among populations that arose following the last Ice Age is a promising method for understanding the potential future effects of climate change. Theoretical and empirical work has suggested that overall genetic diversity can decrease in colonial populations following rapid expansion into postglacial landscapes, with potential negative effects on the ability of populations to adapt to new environmental regimes. The crucial measure of this genetic variation and a population's overall adaptability is the heritable variation in phenotypic traits, as it is this variation that mediates the rate and direction of a population's multigenerational response to selection. Using two large full-sib quantitative genetic studies (N(Manitoba)?=?144; N(South Dakota)?=?653) and a smaller phenotypic analysis from Kansas (N(Kansas)?=?44), we compared mean levels of pigmentation, genetic variation and heritability in three pigmentation traits among populations of the common garter snake, Thamnophis sirtalis, along a north-south gradient, including a postglacial northern population and a putative southern refuge population. Counter to our expectations, we found that genetic variance and heritability for the three pigmentation traits were the same or higher in the postglacial population than in the southern population. PMID:21935386

  15. A Quantitative Analysis of Growth and Size Regulation in Manduca sexta: The Physiological Basis of Variation in Size and Age at Metamorphosis

    PubMed Central

    Grunert, Laura W.; Clarke, Jameson W.; Ahuja, Chaarushi; Eswaran, Harish; Nijhout, H. Frederik

    2015-01-01

    Body size and development time are important life history traits because they are often highly correlated with fitness. Although the developmental mechanisms that control growth have been well studied, the mechanisms that control how a species-characteristic body size is achieved remain poorly understood. In insects adult body size is determined by the number of larval molts, the size increment at each molt, and the mechanism that determines during which instar larval growth will stop. Adult insects do not grow, so the size at which a larva stops growing determines adult body size. Here we develop a quantitative understanding of the kinetics of growth throughout larval life of Manduca sexta, under different conditions of nutrition and temperature, and for genetic strains with different adult body sizes. We show that the generally accepted view that the size increment at each molt is constant (Dyar’s Rule) is systematically violated: there is actually a progressive increase in the size increment from instar to instar that is independent of temperature. In addition, the mass-specific growth rate declines throughout the growth phase in a temperature-dependent manner. We show that growth within an instar follows a truncated Gompertz trajectory. The critical weight, which determines when in an instar a molt will occur, and the threshold size, which determines which instar is the last, are different in genetic strains with different adult body sizes. Under nutrient and temperature stress Manduca has a variable number of larval instars and we show that this is due to the fact that more molts at smaller increments are taken before threshold size is reached. We test whether the new insight into the kinetics of growth and size determination are sufficient to explain body size and development time through a mathematical model that incorporates our quantitative findings. PMID:26011714

  16. Quantitative Effect of a CNV on a Morphological Trait in Chickens

    PubMed Central

    Moro, Céline; Cornette, Raphaël; Vieaud, Agathe; Bruneau, Nicolas; Gourichon, David; Bed’hom, Bertrand; Tixier-Boichard, Michèle

    2015-01-01

    Copy Number Variation has been associated with morphological traits, developmental defects or disease susceptibility. The autosomal dominant Pea-comb mutation in chickens is due to the massive amplification of a CNV in intron 1 of SOX5 and provides a unique opportunity to assess the effect of variation in the number of repeats on quantitative traits such as comb size and comb mass in Pea-comb chickens. The quantitative variation of comb size was estimated by 2D morphometry and the number of repeats (RQ) was estimated by qPCR, in a total of 178 chickens from 3 experimental lines, two of them showing segregation for the Pea-comb mutation. This study included only Pea-comb chickens. Analysis of variance showed highly significant effects of line and sex on comb measurements. Adult body weight (BW) and RQ were handled as covariates. BW significantly influenced comb mass but not comb size. RQ values significantly influenced comb size, and the linear regression coefficient was highest for heterozygous carriers: the higher the number of repeats, the smaller the comb size. A similar trend was observed for comb mass. The CNV contributed to 3.4% of the phenotypic variance of comb size in heterozygous carriers of the CNV, an order of magnitude frequently encountered for QTLs. Surprisingly, there was no such relationship between RQ values and comb size in the homozygous line. It may be concluded that heterozygosity for a CNV in a non-coding region may contribute to phenotypic plasticity. PMID:25768125

  17. Phenotypic plasticity and diversity in insects

    PubMed Central

    Moczek, Armin P.

    2010-01-01

    Phenotypic plasticity in general and polyphenic development in particular are thought to play important roles in organismal diversification and evolutionary innovation. Focusing on the evolutionary developmental biology of insects, and specifically that of horned beetles, I explore the avenues by which phenotypic plasticity and polyphenic development have mediated the origins of novelty and diversity. Specifically, I argue that phenotypic plasticity generates novel targets for evolutionary processes to act on, as well as brings about trade-offs during development and evolution, thereby diversifying evolutionary trajectories available to natural populations. Lastly, I examine the notion that in those cases in which phenotypic plasticity is underlain by modularity in gene expression, it results in a fundamental trade-off between degree of plasticity and mutation accumulation. On one hand, this trade-off limits the extent of plasticity that can be accommodated by modularity of gene expression. On the other hand, it causes genes whose expression is specific to rare environments to accumulate greater variation within species, providing the opportunity for faster divergence and diversification between species, compared with genes expressed across environments. Phenotypic plasticity therefore contributes to organismal diversification on a variety of levels of biological organization, thereby facilitating the evolution of novel traits, new species and complex life cycles. PMID:20083635

  18. Phenotypic approaches to drought in cassava: review

    PubMed Central

    Okogbenin, Emmanuel; Setter, Tim L.; Ferguson, Morag; Mutegi, Rose; Ceballos, Hernan; Olasanmi, Bunmi; Fregene, Martin

    2012-01-01

    Cassava is an important crop in Africa, Asia, Latin America, and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12–18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance breeding. PMID:23717282

  19. Male and female secondary sexual traits show different patterns of quantitative genetic and environmental variation in the horned beetle Onthophagus sagittarius.

    PubMed

    Watson, N L; Simmons, L W

    2010-11-01

    The expression of secondary sexual traits in females has often been attributed to a correlated response to selection on male traits. In rare cases, females have secondary sexual traits that are not homologous structures to secondary sexual traits in males and are thus less likely to have evolved in females because of correlated selection. In this study, we used the dung beetle Onthophagus sagittarius, a species with sex-specific horns, to examine the environmental and quantitative genetic control of horn expression in males and females. Offspring subjected to different brood mass manipulations (dung addition/removal) were found to differ significantly in body size. Brood mass manipulation also had a significant effect on the length of male horns; however, female horn length was found to be relatively impervious to the treatment, showing stronger patterns of additive genetic variance than males. We found no correlations between horn expression in males and females. We therefore conclude that the horns of O. sagittarius females are unlikely to result from genetic correlations between males and females. Rather, our data suggest that they may be under independent genetic control. PMID:20831732

  20. Identification of copy number variations in Qinchuan cattle using BovineHD Genotyping Beadchip array.

    PubMed

    Zhang, Quanwei; Ma, Youji; Wang, Xueying; Zhang, Yong; Zhao, Xingxu

    2015-02-01

    In recent years, copy number variations (CNVs), which associate with complex traits such as disease and quantitative phenotypes, are increasingly recognized as an important and abundant source of genetic variation and phenotypic diversity. CNVs have been studied in several breeds of cattle with the goal of improving selection methods for commercial use; however, little is known about the extent to which CNVs contribute to genetic variation in Qinchuan cattle. The BovineHD Genotyping BeadChip array was used for analyzing the whole genomic CNVs of Qinchuan cattle breed; we discovered 367 unique CNV events from 6 Qinchuan cattle. Accounting for overlapping regions, a total of 365 autosomal copy number variation regions (CNVRs) (131 losses and 234 gains) were identified with an average number of 60.8 CNV events per individual, which covered 13.13 Mb of the cattle genomic sequence corresponding to 0.4 % of the whole cattle genome. The average and median sizes of CNVRs were 35.07 and 18.56 kb, respectively. The CNVRs map of Qinchuan cattle was first constructed based on the BovineHD Genotyping Beadchip array. Functional analysis indicated that most genes in CNVRs that were significantly enriched are involved in environmental stress. Comparison of CNVRs in ten published studies and the 365 CNVRs identified in our study overlapped 0.7-42.7 %. These findings are the first report of CNVs mapping in Qinchuan cattle and contribute to the greater understanding of CNV genetics in commercial cattle phenotypes. PMID:25248638

  1. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Perú and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism.

    PubMed

    Núñez, Vitelbina; Cid, Pedro; Sanz, Libia; De La Torre, Pilar; Angulo, Yamileth; Lomonte, Bruno; Gutiérrez, José María; Calvete, Juan J

    2009-11-01

    The venom proteomes of Bothrops atrox from Colombia, Brazil, Ecuador, and Perú were characterized using venomic and antivenomic strategies. Our results evidence the existence of two geographically differentiated venom phenotypes. The venom from Colombia comprises at least 26 different proteins belonging to 9 different groups of toxins. PI-metalloproteinases and K49-PLA(2) molecules represent the most abundant toxins. On the other hand, the venoms from Brazilian, Ecuadorian, and Peruvian B. atrox contain predominantly PIII-metalloproteinases. These toxin profiles correlate with the venom phenotypes of adult and juvenile B. asper from Costa Rica, respectively, suggesting that paedomorphism represented a selective trend during the trans-Amazonian southward expansion of B. atrox through the Andean Corridor. The high degree of crossreactivity of a Costa Rican polyvalent (Bothrops asper, Lachesis stenophrys, Crotalus simus) antivenom against B. atrox venoms further evidenced the close evolutionary kinship between B. asper and B. atrox. This antivenom was more efficient immunodepleting proteins from the venoms of B. atrox from Brazil, Ecuador, and Perú than from Colombia. Such behaviour may be rationalized taking into account the lower content of poorly immunogenic toxins, such as PLA(2) molecules and PI-SVMPs in the paedomorphic venoms. The immunological profile of the Costa Rican antivenom strongly suggests the possibility of using this antivenom for the management of snakebites by B. atrox in Colombia and the Amazon regions of Ecuador, Perú and Brazil. PMID:19665598

  2. The genomic and phenotypic diversity of Schizosaccharomyces pombe.

    PubMed

    Jeffares, Daniel C; Rallis, Charalampos; Rieux, Adrien; Speed, Doug; P?evorovský, Martin; Mourier, Tobias; Marsellach, Francesc X; Iqbal, Zamin; Lau, Winston; Cheng, Tammy M K; Pracana, Rodrigo; Mülleder, Michael; Lawson, Jonathan L D; Chessel, Anatole; Bala, Sendu; Hellenthal, Garrett; O'Fallon, Brendan; Keane, Thomas; Simpson, Jared T; Bischof, Leanne; Tomiczek, Bartlomiej; Bitton, Danny A; Sideri, Theodora; Codlin, Sandra; Hellberg, Josephine E E U; van Trigt, Laurent; Jeffery, Linda; Li, Juan-Juan; Atkinson, Sophie; Thodberg, Malte; Febrer, Melanie; McLay, Kirsten; Drou, Nizar; Brown, William; Hayles, Jacqueline; Carazo Salas, Rafael E; Ralser, Markus; Maniatis, Nikolas; Balding, David J; Balloux, Francois; Durbin, Richard; Bähler, Jürg

    2015-03-01

    Natural variation within species reveals aspects of genome evolution and function. The fission yeast Schizosaccharomyces pombe is an important model for eukaryotic biology, but researchers typically use one standard laboratory strain. To extend the usefulness of this model, we surveyed the genomic and phenotypic variation in 161 natural isolates. We sequenced the genomes of all strains, finding moderate genetic diversity (? = 3 × 10(-3) substitutions/site) and weak global population structure. We estimate that dispersal of S. pombe began during human antiquity (?340 BCE), and ancestors of these strains reached the Americas at ?1623 CE. We quantified 74 traits, finding substantial heritable phenotypic diversity. We conducted 223 genome-wide association studies, with 89 traits showing at least one association. The most significant variant for each trait explained 22% of the phenotypic variance on average, with indels having larger effects than SNPs. This analysis represents a rich resource to examine genotype-phenotype relationships in a tractable model. PMID:25665008

  3. Quantitative analysis

    PubMed Central

    Nevin, John A.

    1984-01-01

    Quantitative analysis permits the isolation of invariant relations in the study of behavior. The parameters of these relations can serve as higher-order dependent variables in more extensive analyses. These points are illustrated by reference to quantitative descriptions of performance maintained by concurrent schedules, multiple schedules, and signal-detection procedures. Such quantitative descriptions of empirical data may be derived from mathematical theories, which in turn can lead to novel empirical analyses so long as their terms refer to behavioral and environmental events. Thus, quantitative analysis is an integral aspect of the experimental analysis of behavior. PMID:16812400

  4. Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits

    E-print Network

    Zaitlen, Noah

    Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, ...

  5. Lessons from Model Organisms: Phenotypic Robustness and Missing Heritability in Complex Disease

    PubMed Central

    Queitsch, Christine; Carlson, Keisha D.; Girirajan, Santhosh

    2012-01-01

    Genetically tractable model organisms from phages to mice have taught us invaluable lessons about fundamental biological processes and disease-causing mutations. Owing to technological and computational advances, human biology and the causes of human diseases have become accessible as never before. Progress in identifying genetic determinants for human diseases has been most remarkable for Mendelian traits. In contrast, identifying genetic determinants for complex diseases such as diabetes, cancer, and cardiovascular and neurological diseases has remained challenging, despite the fact that these diseases cluster in families. Hundreds of variants associated with complex diseases have been found in genome-wide association studies (GWAS), yet most of these variants explain only a modest amount of the observed heritability, a phenomenon known as “missing heritability.” The missing heritability has been attributed to many factors, mainly inadequacies in genotyping and phenotyping. We argue that lessons learned about complex traits in model organisms offer an alternative explanation for missing heritability in humans. In diverse model organisms, phenotypic robustness differs among individuals, and those with decreased robustness show increased penetrance of mutations and express previously cryptic genetic variation. We propose that phenotypic robustness also differs among humans and that individuals with lower robustness will be more responsive to genetic and environmental perturbations and hence susceptible to disease. Phenotypic robustness is a quantitative trait that can be accurately measured in model organisms, but not as yet in humans. We propose feasible approaches to measure robustness in large human populations, proof-of-principle experiments for robustness markers in model organisms, and a new GWAS design that takes differences in robustness into account. PMID:23166511

  6. Phenotype Ontologies and Cross-Species Analysis for Translational Research

    PubMed Central

    Robinson, Peter N.; Webber, Caleb

    2014-01-01

    The use of model organisms as tools for the investigation of human genetic variation has significantly and rapidly advanced our understanding of the aetiologies underlying hereditary traits. However, while equivalences in the DNA sequence of two species may be readily inferred through evolutionary models, the identification of equivalence in the phenotypic consequences resulting from comparable genetic variation is far from straightforward, limiting the value of the modelling paradigm. In this review, we provide an overview of the emerging statistical and computational approaches to objectively identify phenotypic equivalence between human and model organisms with examples from the vertebrate models, mouse and zebrafish. Firstly, we discuss enrichment approaches, which deem the most frequent phenotype among the orthologues of a set of genes associated with a common human phenotype as the orthologous phenotype, or phenolog, in the model species. Secondly, we introduce and discuss computational reasoning approaches to identify phenotypic equivalences made possible through the development of intra- and interspecies ontologies. Finally, we consider the particular challenges involved in modelling neuropsychiatric disorders, which illustrate many of the remaining difficulties in developing comprehensive and unequivocal interspecies phenotype mappings. PMID:24699242

  7. Quantitative assessment of atmospheric emissions of toxic heavy metals from anthropogenic sources in China: historical trend, spatial variation distribution, uncertainties and control policies

    NASA Astrophysics Data System (ADS)

    Tian, H. Z.; Zhu, C. Y.; Gao, J. J.; Cheng, K.; Hao, J. M.; Wang, K.; Hua, S. B.; Wang, Y.; Zhou, J. R.

    2015-04-01

    Anthropogenic atmospheric emissions of typical toxic heavy metals have received worldwide concerns due to their adverse effects on human health and the ecosystem. By determining the best available representation of time-varying emission factors with S-shape curves, we established the multiyear comprehensive atmospheric emission inventories of 12 typical toxic heavy metals (Hg, As, Se, Pb, Cd, Cr, Ni, Sb, Mn, Co, Cu and Zn) from primary anthropogenic activities in China for the period of 1949-2012 for the first time. Further, we allocated the annual emissions of these heavy metals in 2010 at a high spatial resolution of 0.5° × 0.5° grid with ArcGIS methodology and surrogate indexes, such as regional population and gross domestic product (GDP). Our results show that the historical emissions of Hg, As, Se, Cd, Cr, Ni, Sb, Mn, Co, Cu and Zn during the period of 1949-2012, have been increased by about 22-128 times at an annual average growth rate of 5.1-8.0%, amounting to about 79 570 t in 2012. Nonferrous metal smelting, coal combustion of industrial boilers, brake and tyre wear, and ferrous metals smelting represent the dominant sources for Hg / Cd, As / Se / Pb / Cr / Ni / Mn / Co, Sb / Cu, and Zn, respectively. In terms of spatial variation, the majority of emissions were concentrated in relatively developed regions, especially for the northern, eastern and southern coastal regions. In addition, because of the flourishing nonferrous metals smelting industry, several southwestern and central-southern provinces play a prominent role in some specific toxic heavy metals emissions, like Hg in Guizhou and As in Yunnan. Finally, integrated countermeasures are proposed to minimize the final toxic heavy metals discharge on accounting of the current and future demand of energy-saving and pollution reduction in China.

  8. ORIGINAL ARTICLE Linking transcriptomic and genomic variation to growth

    E-print Network

    Bernatchez, Louis

    ; transcriptomics; cis regulation; epistasis; salmonids INTRODUCTION Hybridization can be an important source- wide patterns of gene expression among populations exhibiting phenotypic variation. In fishes

  9. Protein change in plant evolution: tracing one thread connecting molecular and phenotypic diversity

    PubMed Central

    Bartlett, Madelaine E.; Whipple, Clinton J.

    2013-01-01

    Proteins change over the course of evolutionary time. New protein-coding genes and gene families emerge and diversify, ultimately affecting an organism’s phenotype and interactions with its environment. Here we survey the range of structural protein change observed in plants and review the role these changes have had in the evolution of plant form and function. Verified examples tying evolutionary change in protein structure to phenotypic change remain scarce. We will review the existing examples, as well as draw from investigations into domestication, and quantitative trait locus (QTL) cloning studies searching for the molecular underpinnings of natural variation. The evolutionary significance of many cloned QTL has not been assessed, but all the examples identified so far have begun to reveal the extent of protein structural diversity tolerated in natural systems. This molecular (and phenotypic) diversity could come to represent part of natural selection’s source material in the adaptive evolution of novel traits. Protein structure and function can change in many distinct ways, but the changes we identified in studies of natural diversity and protein evolution were predicted to fall primarily into one of six categories: altered active and binding sites; altered protein–protein interactions; altered domain content; altered activity as an activator or repressor; altered protein stability; and hypomorphic and hypermorphic alleles. There was also variability in the evolutionary scale at which particular changes were observed. Some changes were detected at both micro- and macroevolutionary timescales, while others were observed primarily at deep or shallow phylogenetic levels. This variation might be used to determine the trajectory of future investigations in structural molecular evolution. PMID:24124420

  10. Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit

    PubMed Central

    Klee, Eric W.; Shin, Andrea; Carlson, Paula; Li, Ying; Grover, Madhusudan; Zinsmeister, Alan R.

    2013-01-01

    The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D (n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes (ASBT, FXR, OST?/?, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6). Exome findings were compared with those of 50 similar ethnicity controls. We assessed univariate associations of each SNV with quantitative traits and a principal components analysis and associations between SNVs in KLB and FGFR4 and symptom phenotype in 405 IBS, 228 controls and colonic transit in 70 IBS-D, 71 IBS-constipation. Mining the complete exome did not reveal significant associations with IBS-D over controls. There were 54 SNVs in 10 of 11 bile acid-regulating genes, with no SNVs in FGF19; 15 nonsynonymous SNVs were identified in similar proportions of IBS-D and controls. Variations in KLB (rs1015450, downstream) and FGFR4 [rs434434 (intronic), rs1966265, and rs351855 (nonsynonymous)] were associated with colonic transit (rs1966265; P = 0.043), fecal bile acids (rs1015450; P = 0.064), and principal components analysis groups (all 3 FGFR4 SNVs; P < 0.05). In the 633-person cohort, FGFR4 rs434434 was associated with symptom phenotype (P = 0.027) and rs1966265 with 24-h colonic transit (P = 0.066). Thus exome sequencing identified additional variants in KLB and FGFR4 associated with bile acids or colonic transit in IBS-D. PMID:24200957

  11. Precision phenotyping of imidazolinone-induced chlorosis in sunflower.

    PubMed

    Ochogavía, Ana Claudia; Gil, Mercedes; Picardi, Liliana; Nestares, Graciela

    2014-12-01

    Chlorosis level is a useful parameter to assess imidazolinone resistance in sunflower (Helianthus annuus L.). The aim of this study was to quantify chlorosis through two different methods in sunflower plantlets treated with imazapyr. The genotypes used in this study were two inbred lines reported to be different in their resistance to imidazolinones. Chlorosis was evaluated by spectrophotometrical quantification of photosynthetic leaf pigments and by a bioinformatics-based color analysis. A protocol for pigment extraction was presented which improved pigment stability. Chlorophyll amount decreased significantly when both genotypes were treated with 10 ?M of imazapyr. Leaf color was characterized using Tomato Analyzer(®) color test software. A significant positive correlation between color reduction and chlorophyll concentration was found. It suggests that leaf color measurement could be an accurate method to estimate chlorosis and infer chlorophyll levels in sunflower plants. These results highlight a strong relationship between imidazolinone-induced chlorosis and variations in leaf color and in chlorophyll concentration. Both methods are quantitative, rapid, simple, and reproducible. Thus, they could be useful tools for phenotyping and screening large number of plants when breeding for imidazolinone resistance in this species. PMID:25914598

  12. Rat Genome Database: a unique resource for rat, human, and mouse quantitative trait locus data

    PubMed Central

    Laulederkind, Stanley J. F.; Hayman, G. Thomas; Smith, Jennifer R.; Wang, Shur-Jen; Lowry, Timothy F.; Petri, Victoria; Pons, Jeff De; Tutaj, Marek; Liu, Weisong; Jayaraman, Pushkala; Munzenmaier, Diane H.; Worthey, Elizabeth A.; Dwinell, Melinda R.; Shimoyama, Mary; Jacob, Howard J.

    2013-01-01

    The rat has been widely used as a disease model in a laboratory setting, resulting in an abundance of genetic and phenotype data from a wide variety of studies. These data can be found at the Rat Genome Database (RGD, http://rgd.mcw.edu/), which provides a platform for researchers interested in linking genomic variations to phenotypes. Quantitative trait loci (QTLs) form one of the earliest and core datasets, allowing researchers to identify loci harboring genes associated with disease. These QTLs are not only important for those using the rat to identify genes and regions associated with disease, but also for cross-organism analyses of syntenic regions on the mouse and the human genomes to identify potential regions for study in these organisms. Currently, RGD has data on >1,900 rat QTLs that include details about the methods and animals used to determine the respective QTL along with the genomic positions and markers that define the region. RGD also curates human QTLs (>1,900) and houses >4,000 mouse QTLs (imported from Mouse Genome Informatics). Multiple ontologies are used to standardize traits, phenotypes, diseases, and experimental methods to facilitate queries, analyses, and cross-organism comparisons. QTLs are visualized in tools such as GBrowse and GViewer, with additional tools for analysis of gene sets within QTL regions. The QTL data at RGD provide valuable information for the study of mapped phenotypes and identification of candidate genes for disease associations. PMID:23881287

  13. Broad network-based predictability of Saccharomyces cerevisiae gene loss-of-function phenotypes

    Microsoft Academic Search

    Kriston L McGary; Insuk Lee; Edward M Marcotte

    2007-01-01

    We demonstrate that loss-of-function yeast phenotypes are predictable by guilt-by-association in functional gene networks. Testing 1,102 loss-of-function phenotypes from genome-wide assays of yeast reveals predictability of diverse phenotypes, spanning cellular morphology, growth, metabolism, and quantitative cell shape features. We apply the method to extend a genome-wide screen by predicting, then verifying, genes whose disruption elongates yeast cells, and to predict

  14. Complex epilepsy phenotype extraction from narrative clinical discharge summaries

    PubMed Central

    Cui, Licong; Sahoo, Satya S.; Lhatoo, Samden D.; Garg, Gaurav; Rai, Prashant; Bozorgi, Alireza; Zhang, Guo-Qiang

    2015-01-01

    Epilepsy is a common serious neurological disorder with a complex set of possible phenotypes ranging from pathologic abnormalities to variations in electroencephalogram. This paper presents a system called Phenotype Exaction in Epilepsy (PEEP) for extracting complex epilepsy phenotypes and their correlated anatomical locations from clinical discharge summaries, a primary data source for this purpose. PEEP generates candidate phenotype and anatomical location pairs by embedding a named entity recognition method, based on the Epilepsy and Seizure Ontology, into the National Library of Medicine's MetaMap program. Such candidate pairs are further processed using a correlation algorithm. The derived phenotypes and correlated locations have been used for cohort identification with an integrated ontology-driven visual query interface. To evaluate the performance of PEEP, 400 de-identified discharge summaries were used for development and an additional 262 were used as test data. PEEP achieved a micro-averaged precision of 0.924, recall of 0.931, and F1-measure of 0.927 for extracting epilepsy phenotypes. The performance on the extraction of correlated phenotypes and anatomical locations shows a micro-averaged F1-measure of 0.856 (Precision: 0.852, Recall: 0.859). The evaluation demonstrates that PEEP is an effective approach to extracting complex epilepsy phenotypes for cohort identification. PMID:24973735

  15. Complex epilepsy phenotype extraction from narrative clinical discharge summaries.

    PubMed

    Cui, Licong; Sahoo, Satya S; Lhatoo, Samden D; Garg, Gaurav; Rai, Prashant; Bozorgi, Alireza; Zhang, Guo-Qiang

    2014-10-01

    Epilepsy is a common serious neurological disorder with a complex set of possible phenotypes ranging from pathologic abnormalities to variations in electroencephalogram. This paper presents a system called Phenotype Exaction in Epilepsy (PEEP) for extracting complex epilepsy phenotypes and their correlated anatomical locations from clinical discharge summaries, a primary data source for this purpose. PEEP generates candidate phenotype and anatomical location pairs by embedding a named entity recognition method, based on the Epilepsy and Seizure Ontology, into the National Library of Medicine's MetaMap program. Such candidate pairs are further processed using a correlation algorithm. The derived phenotypes and correlated locations have been used for cohort identification with an integrated ontology-driven visual query interface. To evaluate the performance of PEEP, 400 de-identified discharge summaries were used for development and an additional 262 were used as test data. PEEP achieved a micro-averaged precision of 0.924, recall of 0.931, and F1-measure of 0.927 for extracting epilepsy phenotypes. The performance on the extraction of correlated phenotypes and anatomical locations shows a micro-averaged F1-measure of 0.856 (Precision: 0.852, Recall: 0.859). The evaluation demonstrates that PEEP is an effective approach to extracting complex epilepsy phenotypes for cohort identification. PMID:24973735

  16. Estimation of Genetic Effects and Genotype-Phenotype Maps

    PubMed Central

    Le Rouzic, Arnaud; Álvarez-Castro, José M.

    2008-01-01

    Determining the genetic architecture of complex traits is a necessary step to understand phenotypic changes in natural, experimental and domestic populations. However, this is still a major challenge for modern genetics, since the estimation of genetic effects tends to be complicated by genetic interactions, which lead to changes in the effect of allelic substitutions depending on the genetic background. Recent progress in statistical tools aiming to describe and quantify genetic effects meaningfully improves the efficiency and the availability of genotype-to-phenotype mapping methods. In this contribution, we facilitate the practical use of the recently published ‘NOIA’ quantitative framework by providing an implementation of linear and multilinear regressions, change of reference operation and genotype-to-phenotype mapping in a package (‘noia’) for the software R, and we discuss theoretical and practical benefits evolutionary and quantitative geneticists may find in using proper modeling strategies to quantify the effects of genes. PMID:19204820

  17. Systematic Screening of Drosophila Deficiency Mutations for Embryonic Phenotypes and Orphan Receptor Ligands

    Microsoft Academic Search

    Ashley P. Wright; A. Nicole Fox; Karl G. Johnson; Kai Zinn; Brian D. McCabe

    2010-01-01

    This paper defines a collection of Drosophila deletion mutations (deficiencies) that can be systematically screened for embryonic phenotypes, orphan receptor ligands, and genes affecting protein localization. It reports the results of deficiency screens we have conducted that have revealed new axon guidance phenotypes in the central nervous system and neuromuscular system and permitted a quantitative assessment of the number of

  18. Generating Phenotypic Diversity in a Fungal Biocatalyst to Investigate Alcohol Stress Tolerance Encountered during Microbial Cellulosic Biofuel Production

    PubMed Central

    Hennessy, Rosanna C.; Doohan, Fiona; Mullins, Ewen

    2013-01-01

    Consolidated bioprocessing (CBP) of lignocellulosic biomass offers an alternative route to renewable energy. The crop pathogen Fusarium oxysporum is a promising fungal biocatalyst because of its broad host range and innate ability to co-saccharify and ferment lignocellulose to bioethanol. A major challenge for cellulolytic CBP-enabling microbes is alcohol inhibition. This research tested the hypothesis that Agrobacterium tumefaciens - mediated transformation (ATMT) could be exploited as a tool to generate phenotypic diversity in F. oxysporum to investigate alcohol stress tolerance encountered during CBP. A random mutagenesis library of gene disruption transformants (n=1,563) was constructed and screened for alcohol tolerance in order to isolate alcohol sensitive or tolerant phenotypes. Following three rounds of screening, exposure of select transformants to 6% ethanol and 0.75% n-butanol resulted respectively in increased (?11.74%) and decreased (?43.01%) growth compared to the wild –type (WT). Principal component analysis (PCA) quantified the level of phenotypic diversity across the population of genetically transformed individuals and isolated candidate strains for analysis. Characterisation of one strain, Tr. 259, ascertained a reduced growth phenotype under alcohol stress relative to WT and indicated the disruption of a coding region homologous to a putative sugar transporter (FOXG_09625). Quantitative PCR (RT-PCR) showed FOXG_09625 was differentially expressed in Tr. 259 compared to WT during alcohol-induced stress (P<0.05). Phylogenetic analysis of putative sugar transporters suggests diverse functional roles in F. oxysporum and other filamentous fungi compared to yeast for which sugar transporters form part of a relatively conserved family. This study has confirmed the potential of ATMT coupled with a phenotypic screening program to select for genetic variation induced in response to alcohol stress. This research represents a first step in the investigation of alcohol tolerance in F. oxysporum and has resulted in the identification of several novel strains, which will be of benefit to future biofuel research. PMID:24147009

  19. Generating phenotypic diversity in a fungal biocatalyst to investigate alcohol stress tolerance encountered during microbial cellulosic biofuel production.

    PubMed

    Hennessy, Rosanna C; Doohan, Fiona; Mullins, Ewen

    2013-01-01

    Consolidated bioprocessing (CBP) of lignocellulosic biomass offers an alternative route to renewable energy. The crop pathogen Fusarium oxysporum is a promising fungal biocatalyst because of its broad host range and innate ability to co-saccharify and ferment lignocellulose to bioethanol. A major challenge for cellulolytic CBP-enabling microbes is alcohol inhibition. This research tested the hypothesis that Agrobacterium tumefaciens--mediated transformation (ATMT) could be exploited as a tool to generate phenotypic diversity in F. oxysporum to investigate alcohol stress tolerance encountered during CBP. A random mutagenesis library of gene disruption transformants (n=1,563) was constructed and screened for alcohol tolerance in order to isolate alcohol sensitive or tolerant phenotypes. Following three rounds of screening, exposure of select transformants to 6% ethanol and 0.75% n-butanol resulted respectively in increased (? 11.74%) and decreased (? 43.01%) growth compared to the wild -type (WT). Principal component analysis (PCA) quantified the level of phenotypic diversity across the population of genetically transformed individuals and isolated candidate strains for analysis. Characterisation of one strain, Tr. 259, ascertained a reduced growth phenotype under alcohol stress relative to WT and indicated the disruption of a coding region homologous to a putative sugar transporter (FOXG_09625). Quantitative PCR (RT-PCR) showed FOXG_09625 was differentially expressed in Tr. 259 compared to WT during alcohol-induced stress (P<0.05). Phylogenetic analysis of putative sugar transporters suggests diverse functional roles in F. oxysporum and other filamentous fungi compared to yeast for which sugar transporters form part of a relatively conserved family. This study has confirmed the potential of ATMT coupled with a phenotypic screening program to select for genetic variation induced in response to alcohol stress. This research represents a first step in the investigation of alcohol tolerance in F. oxysporum and has resulted in the identification of several novel strains, which will be of benefit to future biofuel research. PMID:24147009

  20. Genome Size Scaling through Phenotype Space

    PubMed Central

    Knight, Charles A.; Beaulieu, Jeremy M.

    2008-01-01

    Background and Aims Early observations that genome size was positively correlated with cell size formed the basis of hypothesized consequences of genome size variation at higher phenotypic scales. This scaling was supported by several studies showing a positive relationship between genome size and seed mass, and various metrics of growth and leaf morphology. However, many of these studies were undertaken with limited species sets, and often performed within a single genus. Here we seek to generalize the relationship between genome size and the phenotype by examining eight phenotypic traits using large cross-species comparisons involving diverse assemblages of angiosperm and gymnosperm species. These analyses are presented in order of increasing scale (roughly equating to the number of cells required to produce a particular phenotypic trait), following the order of: cell size (guard cell and epidermal), stomatal density, seed mass, leaf mass per unit area (LMA), wood density, photosynthetic rate and finally maximum plant height. Scope The results show that genome size is a strong predictor of phenotypic traits at the cellular level (guard cell length and epidermal cell area had significant positive relationships with genome size). Stomatal density decreased with increasing genome size, but this did not lead to decreased photosynthetic rate. At higher phenotypic scales, the predictive power of genome size generally diminishes (genome size had weak predictive power for both LMA and seed mass), except in the interesting case of maximum plant height (tree species tend to have small genomes). There was no relationship with wood density. The general observation that species with larger genome size have larger seed mass was supported; however, species with small genome size can also have large seed masses. All of these analyses involved robust comparative methods that incorporate the phylogenetic relationships of species. Conclusions Genome size correlations are quite strong at the cellular level but decrease in predictive power with increasing phenotypic scale. Our hope is that these results may lead to new mechanistic hypotheses about why genome size scaling exists at the cellular level, and why nucleotypic consequences diminish at higher phenotypic scales. PMID:18222911

  1. Familial Aggregation of Dyslexia Phenotypes

    Microsoft Academic Search

    Wendy H. Raskind; Li Hsu; Virginia W. Berninger; Jennifer B. Thomson; Ellen M. Wijsman

    2000-01-01

    There is evidence for genetic contributions to reading disability, but the phenotypic heterogeneity associated with the clinical diagnosis may make identification of the underlying genetic basis difficult. In order to elucidate distinct phenotypic features that may be contributing to the genotypic heterogeneity, we assessed the familial aggregation patterns of Verbal IQ and 24 phenotypic measures associated with dyslexia in 102

  2. Mapping quantitative trait loci with dominant and missing markers in various crosses from two inbred lines

    Microsoft Academic Search

    Changjian Jiang; Zhao-Bang Zeng

    1997-01-01

    Dominant phenotype of a genetic marker provides incomplete information about the marker genotype of an individual. A consequence of using this incomplete information for mapping quantitative trait loci (QTL) is that the inference of the genotype of a putative QTL flanked by a marker with dominant phenotype will depend on the genotype or phenotype of the next marker. This dependence

  3. Hormones and phenotypic plasticity in an ecological context: linking physiological mechanisms to evolutionary processes.

    PubMed

    Lema, Sean C

    2014-11-01

    Hormones are chemical signaling molecules that regulate patterns of cellular physiology and gene expression underlying phenotypic traits. Hormone-signaling pathways respond to an organism's external environment to mediate developmental stage-specific malleability in phenotypes, so that environmental variation experienced at different stages of development has distinct effects on an organism's phenotype. Studies of hormone-signaling are therefore playing a central role in efforts to understand how plastic phenotypic responses to environmental variation are generated during development. But, how do adaptive, hormonally mediated phenotypes evolve if the individual signaling components (hormones, conversion enzymes, membrane transporters, and receptors) that comprise any hormone-signaling pathway show expressional flexibility in response to environmental variation? What relevance do these components hold as molecular targets for selection to couple or decouple correlated hormonally mediated traits? This article explores how studying the endocrine underpinnings of phenotypic plasticity in an ecologically relevant context can provide insights into these, and other, crucial questions into the role of phenotypic plasticity in evolution, including how plasticity itself evolves. These issues are discussed in the light of investigations into how thyroid hormones mediate morphological plasticity in Death Valley's clade of pupfishes (Cyprinodon spp.). Findings from this work with pupfish illustrate that the study of hormone-signaling from an ecological perspective can reveal how phenotypic plasticity contributes to the generation of phenotypic novelty, as well as how physiological mechanisms developmentally link an organism's phenotype to its environmental experiences. PMID:24752548

  4. The allergic asthma phenotype.

    PubMed

    Schatz, Michael; Rosenwasser, Lanny

    2014-01-01

    Allergic asthma is the most common asthma phenotype. It usually is defined by the presence of sensitization to environmental allergens, although a clinical correlation between exposure and symptoms further supports the diagnosis. The average age of onset of allergic asthma is younger than that of nonallergic asthma. Although the spectrum of allergic asthma may vary from mild to severe, studies have reported that allergic versus nonallergic asthma is less severe. There is an increased prevalence of allergic rhinoconjunctivitis and atopic dermatitis in patients with allergic asthma. Total IgE levels usually are higher in allergic versus nonallergic asthma, but levels substantially overlap between the 2 groups. Increased Th2 cytokines have been demonstrated in secretions and peripheral blood of patients with allergic asthma. Atopy has been reported to be inversely associated with persistent airflow obstruction and airway remodeling. Clusters with a high prevalence of early onset atopic asthma have been frequently reported in statistical phenotyping studies, but the various clusters of patients with atopy were quite heterogeneous in terms of symptom severity, pulmonary function, and tendency for exacerbations. Implications for future research regarding the allergic asthma phenotype are described. PMID:25439351

  5. On Quantitizing

    PubMed Central

    Sandelowski, Margarete; Voils, Corrine I.; Knafl, George

    2009-01-01

    Quantitizing, commonly understood to refer to the numerical translation, transformation, or conversion of qualitative data, has become a staple of mixed methods research. Typically glossed are the foundational assumptions, judgments, and compromises involved in converting disparate data sets into each other and whether such conversions advance inquiry. Among these assumptions are that qualitative and quantitative data constitute two kinds of data, that quantitizing constitutes a unidirectional process essentially different from qualitizing, and that counting is an unambiguous process. Among the judgments are deciding what and how to count. Among the compromises are balancing numerical precision with narrative complexity. The standpoints of “conditional complementarity,” “critical remediation,” and “analytic alternation” clarify the added value of converting qualitative data into quantitative form. PMID:19865603

  6. Limited plasticity in the phenotypic variance-covariance matrix for male advertisement calls in the black field cricket, Teleogryllus commodus

    PubMed Central

    Pitchers, W. R.; Brooks, R.; Jennions, M. D.; Tregenza, T.; Dworkin, I.; Hunt, J.

    2013-01-01

    Phenotypic integration and plasticity are central to our understanding of how complex phenotypic traits evolve. Evolutionary change in complex quantitative traits can be predicted using the multivariate breeders’ equation, but such predictions are only accurate if the matrices involved are stable over evolutionary time. Recent work, however, suggests that these matrices are temporally plastic, spatially variable and themselves evolvable. The data available on phenotypic variance-covariance matrix (P) stability is sparse, and largely focused on morphological traits. Here we compared P for the structure of the complex sexual advertisement call of six divergent allopatric populations of the Australian black field cricket, Teleogryllus commodus. We measured a subset of calls from wild-caught crickets from each of the populations and then a second subset after rearing crickets under common-garden conditions for three generations. In a second experiment, crickets from each population were reared in the laboratory on high- and low-nutrient diets and their calls recorded. In both experiments, we estimated P for call traits and used multiple methods to compare them statistically (Flury hierarchy, geometric subspace comparisons and random skewers). Despite considerable variation in means and variances of individual call traits, the structure of P was largely conserved among populations, across generations and between our rearing diets. Our finding that P remains largely stable, among populations and between environmental conditions, suggests that selection has preserved the structure of call traits in order that they can function as an integrated unit. PMID:23530814

  7. Genetic and genomic approaches to assess adaptive genetic variation in plants: forest trees as a model.

    PubMed

    Gailing, Oliver; Vornam, Barbara; Leinemann, Ludger; Finkeldey, Reiner

    2009-12-01

    With the increasing availability of sequence information at putatively important genes or regulatory regions, the characterization of adaptive genetic diversity and their association with phenotypic trait variation becomes feasible for many non-model organisms such as forest trees. Especially in predominantly outcrossing forest tree populations with large effective size, a high genetic variation in relevant genes is maintained, that is the raw material for the adaptation to changing and variable environments, and likewise for plant breeding. Oaks (Quercus spp.) are excellent model species to study the adaptation of forest trees to changing environments. They show a wide geographic distribution in Europe as dominant tree species in many forests and grow under a wide range of climatic and edaphic conditions. With the availability of a growing amount of functional and expressional candidate genes, we are now able to test the functional importance of single nucleotide polymorphisms (SNPs) by associating nucleotide variation in these genes with phenotypic variation in adaptive traits in segregating or natural populations. Here, we report on quantitative trait locus (QTL), candidate gene and association mapping approaches that are applicable to characterize gene markers and SNPs associated with variation in adaptive traits, such as bud burst, drought resistance and other traits showing selective responses to environmental change and stress. Because genome-wide association mapping studies are not feasible because of the enormous amount of SNP markers required in outcrossing trees with high recombination rates, the success of such an approach depends largely on the reasonable selection of candidate genes. PMID:19627554

  8. METHODOLOGY Open Access High throughput quantitative phenotyping of

    E-print Network

    Paris-Sud XI, Université de

    chlorophyll fluorescence image analysis Céline Rousseau1,2,3 , Etienne Belin4 , Edouard Bove1,2,3 , David Rousseau4,5 , Frédéric Fabre6 , Romain Berruyer1,2,3 , Jacky Guillaumès1,2,3 , Charles Manceau7 , Marie

  9. 3D Laser Triangulation for Plant Phenotyping in Challenging Environments.

    PubMed

    Kjaer, Katrine Heinsvig; Ottosen, Carl-Otto

    2015-01-01

    To increase the understanding of how the plant phenotype is formed by genotype and environmental interactions, simple and robust high-throughput plant phenotyping methods should be developed and considered. This would not only broaden the application range of phenotyping in the plant research community, but also increase the ability for researchers to study plants in their natural environments. By studying plants in their natural environment in high temporal resolution, more knowledge on how multiple stresses interact in defining the plant phenotype could lead to a better understanding of the interaction between plant responses and epigenetic regulation. In the present paper, we evaluate a commercial 3D NIR-laser scanner (PlantEye, Phenospex B.V., Herleen, The Netherlands) to track daily changes in plant growth with high precision in challenging environments. Firstly, we demonstrate that the NIR laser beam of the scanner does not affect plant photosynthetic performance. Secondly, we demonstrate that it is possible to estimate phenotypic variation amongst the growth pattern of ten genotypes of Brassica napus L. (rapeseed), using a simple linear correlation between scanned parameters and destructive growth measurements. Our results demonstrate the high potential of 3D laser triangulation for simple measurements of phenotypic variation in challenging environments and in a high temporal resolution. PMID:26066990

  10. Molecular and phenotypic characterization of atypical Williams-Beuren syndrome.

    PubMed

    Euteneuer, J; Carvalho, C M B; Kulkarni, S; Vineyard, M; Grady, R Mark; Lupski, J R; Shinawi, M

    2014-11-01

    Williams-Beuren syndrome (WBS) is a multisystemic genomic disorder typically caused by a recurrent ˜1.5-1.8?Mb deletion on 7q11.23. Atypical deletions can provide important insight into the genotype-phenotype correlations. Here, we report the phenotypic and molecular characterization of a girl with a de novo 81.8?kb deletion in the WBS critical region, which involves the ELN and LIMK1 genes only. The patient presented at 2?months of age with extensive vascular abnormalities, mild facial dysmorphism and delays in her fine motor skills. We discuss potential molecular mechanisms and the role of ELN and LIMK1 in the different phenotypic features. We compare the findings in our patient with previously reported overlapping deletions. The phenotypic variability among these patients suggests that other factors are important in the phenotype and possibly include: position effects related to copy number variation size, variations in the non-deleted alleles, genetic modifiers elsewhere in the genome, or reduced penetrance for specific phenotypes. PMID:24246242

  11. Sources of floral scent variation

    PubMed Central

    Raguso, Robert A; Ashman, Tia-Lynn

    2009-01-01

    Studies of floral scent generally assume that genetic adaptation due to pollinator-mediated natural selection explains a significant amount of phenotypic variance, ignoring the potential for phenotypic plasticity in this trait. In this paper, we assess this latter possibility, looking first at previous studies of floral scent variation in relation to abiotic environmental factors. We then present data from our own research that suggests among-population floral scent variation is determined, in part, by environmental conditions and thus displays phenotypic plasticity. Such an outcome has strong ramifications for the study of floral scent variation; we conclude by presenting some fundamental questions that should lead to greater insight into our understanding of the evolution of this trait, which is important to plant-animal interactions. PMID:19649189

  12. Kernel methods for phenotyping complex plant architecture.

    PubMed

    Kawamura, Koji; Hibrand-Saint Oyant, Laurence; Foucher, Fabrice; Thouroude, Tatiana; Loustau, Sébastien

    2014-02-01

    The Quantitative Trait Loci (QTL) mapping of plant architecture is a critical step for understanding the genetic determinism of plant architecture. Previous studies adopted simple measurements, such as plant-height, stem-diameter and branching-intensity for QTL mapping of plant architecture. Many of these quantitative traits were generally correlated to each other, which give rise to statistical problem in the detection of QTL. We aim to test the applicability of kernel methods to phenotyping inflorescence architecture and its QTL mapping. We first test Kernel Principal Component Analysis (KPCA) and Support Vector Machines (SVM) over an artificial dataset of simulated inflorescences with different types of flower distribution, which is coded as a sequence of flower-number per node along a shoot. The ability of discriminating the different inflorescence types by SVM and KPCA is illustrated. We then apply the KPCA representation to the real dataset of rose inflorescence shoots (n=1460) obtained from a 98 F1 hybrid mapping population. We find kernel principal components with high heritability (>0.7), and the QTL analysis identifies a new QTL, which was not detected by a trait-by-trait analysis of simple architectural measurements. The main tools developed in this paper could be use to tackle the general problem of QTL mapping of complex (sequences, 3D structure, graphs) phenotypic traits. PMID:24211258

  13. Modifier genes play a significant role in the phenotypic expression of PKD11

    Microsoft Academic Search

    Pamela R. Fain; Kimberly K. McFann; Matthew R. G. Taylor; MARYELLYN TISON; Ann M. Johnson; BERENICE REED; Robert W. Schrier

    2005-01-01

    Modifier genes play a significant role in the phenotypic expression of PKD1.BackgroundPolycystic kidney disease type 1 (PKD1) is characterized by extreme variation in the severity and progression of renal and extrarenal phenotypes. There are significant familial phenotype differences; but it is not clear if this is due to differences in PKD1 mutations, differences in genetic background, or both.MethodsA total of

  14. Effects of egg size on Double-crested Cormorant ( Phalacrocorax auritus) egg composition and hatchling phenotype

    Microsoft Academic Search

    Edward M. Dzialowski; Wendy L. Reed; Paul R. Sotherland

    2009-01-01

    Maternal investment of yolk and albumen in avian eggs varies with egg mass and contributes to variation in hatchling mass. Here we use the natural variation in mass and composition of Double-crested Cormorant (Phalacrocorax auritus) eggs to examine consequences of variation in yolk and albumen mass on hatchling phenotype. The Double-crested Cormorant, a large bird with altricial young, lays eggs

  15. Quantitative trait loci for adult-plant resistance to Mycosphaerella graminicola in two winter wheat populations.

    PubMed

    Risser, P; Ebmeyer, E; Korzun, V; Hartl, L; Miedaner, T

    2011-10-01

    Septoria tritici blotch (STB) is one of the most important leaf spot diseases in wheat worldwide. The goal of this study was to detect chromosomal regions for adult-plant resistance in large winter wheat populations to STB. Inoculation by two isolates with virulence to Stb6 and Stb15, both present in the parents, was performed and STB severity was visually scored plotwise as percent coverage of flag leaves with pycnidia-bearing lesions. 'Florett'/'Biscay' and 'Tuareg'/'Biscay', each comprising a cross of a resistant and a susceptible cultivar, with population sizes of 316 and 269 F(7:8) recombinant inbred lines, respectively, were phenotyped across four and five environments and mapped with amplified fragment length polymorphism, diversity array technology, and simple sequence repeat markers covering polymorphic regions of ?1,340 centimorgans. Phenotypic data revealed significant (P < 0.01) genotypic differentiation for STB, heading date, and plant height. Entry-mean heritabilities (h(2)) for STB were 0.73 for 'Florett'/'Biscay' and 0.38 for 'Tuareg'/'Biscay'. All correlations between STB and heading date as well as between STB and plant height were low (r = -0.13 to -0.20). In quantitative trait loci (QTL) analysis, nine and six QTL were found for STB ratings explaining, together, 55 and 51% of phenotypic variation in 'Florett'/'Biscay' and 'Tuareg'/'Biscay', respectively. Genotype-environment and QTL-environment interactions had a large impact. Two major QTL were detected consistently across environments on chromosomes 3B and 6D from 'Florett' and chromosomes 4B and 6B from 'Tuareg', each explaining 12 to 17% of normalized adjusted phenotypic variance. These results indicate that adult-plant resistance to STB in both mapping populations was of a quantitative nature. PMID:21635143

  16. Population-based resequencing of experimentally evolved populations reveals the genetic basis of body size variation in Drosophila melanogaster.

    PubMed

    Turner, Thomas L; Stewart, Andrew D; Fields, Andrew T; Rice, William R; Tarone, Aaron M

    2011-03-01

    Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size. PMID:21437274

  17. Phylogenetic distribution of phenotypic traits in Bacillus thuringiensis determined by multilocus sequence analysis.

    PubMed

    Blackburn, Michael B; Martin, Phyllis A W; Kuhar, Daniel; Farrar, Robert R; Gundersen-Rindal, Dawn E

    2013-01-01

    Diverse isolates from a world-wide collection of Bacillus thuringiensis were classified based on phenotypic profiles resulting from six biochemical tests; production of amylase (T), lecithinase (L), urease (U), acid from sucrose (S) and salicin (A), and the hydrolysis of esculin (E). Eighty two isolates representing the 15 most common phenotypic profiles were subjected to phylogenetic analysis by multilocus sequence typing; these were found to be distributed among 19 sequence types, 8 of which were novel. Approximately 70% of the isolates belonged to sequence types corresponding to the classical B. thuringiensis varieties kurstaki (20 isolates), finitimus (15 isolates), morrisoni (11 isolates) and israelensis (11 isolates). Generally, there was little apparent correlation between phenotypic traits and phylogenetic position, and phenotypic variation was often substantial within a sequence type. Isolates of the sequence type corresponding to kurstaki displayed the greatest apparent phenotypic variation with 6 of the 15 phenotypic profiles represented. Despite the phenotypic variation often observed within a given sequence type, certain phenotypes appeared highly correlated with particular sequence types. Isolates with the phenotypic profiles TLUAE and LSAE were found to be exclusively associated with sequence types associated with varieties kurstaki and finitimus, respectively, and 7 of 8 TS isolates were found to be associated with the morrisoni sequence type. Our results suggest that the B. thuringiensis varieties israelensis and kurstaki represent the most abundant varieties of Bt in soil. PMID:23762464

  18. Phylogenetic Distribution of Phenotypic Traits in Bacillus thuringiensis Determined by Multilocus Sequence Analysis

    PubMed Central

    Blackburn, Michael B.; Martin, Phyllis A. W.; Kuhar, Daniel; Farrar, Robert R.; Gundersen-Rindal, Dawn E.

    2013-01-01

    Diverse isolates from a world-wide collection of Bacillus thuringiensis were classified based on phenotypic profiles resulting from six biochemical tests; production of amylase (T), lecithinase (L), urease (U), acid from sucrose (S) and salicin (A), and the hydrolysis of esculin (E). Eighty two isolates representing the 15 most common phenotypic profiles were subjected to phylogenetic analysis by multilocus sequence typing; these were found to be distributed among 19 sequence types, 8 of which were novel. Approximately 70% of the isolates belonged to sequence types corresponding to the classical B. thuringiensis varieties kurstaki (20 isolates), finitimus (15 isolates), morrisoni (11 isolates) and israelensis (11 isolates). Generally, there was little apparent correlation between phenotypic traits and phylogenetic position, and phenotypic variation was often substantial within a sequence type. Isolates of the sequence type corresponding to kurstaki displayed the greatest apparent phenotypic variation with 6 of the 15 phenotypic profiles represented. Despite the phenotypic variation often observed within a given sequence type, certain phenotypes appeared highly correlated with particular sequence types. Isolates with the phenotypic profiles TLUAE and LSAE were found to be exclusively associated with sequence types associated with varieties kurstaki and finitimus, respectively, and 7 of 8 TS isolates were found to be associated with the morrisoni sequence type. Our results suggest that the B. thuringiensis varieties israelensis and kurstaki represent the most abundant varieties of Bt in soil. PMID:23762464

  19. From Phenotype to Genotype

    PubMed Central

    2014-01-01

    The progress in phenotype descriptions, measurements, and analyses has been remarkable in the last 50 years. Biomarkers (proteins, carbohydrates, lipids, hormones, various RNAs and cDNAs, microarrays) have been discovered and correlated with diseases and disorders, as well as physiological responses to disease, injury, stress, within blood, urine, and saliva. Three-dimensional digital imaging advanced how we “see” and utilize phenotypes toward diagnosis, treatment, and prognosis. In each example, scientific discovery led to inform clinical health care. In tandem, genetics evolved from Mendelian inheritance (single gene mutations) to include Complex Human Diseases (multiple gene-gene and gene-environment interactions). In addition, epigenetics blossomed with new insights about gene modifiers (e.g., histone and non-histone chromosomal protein methylation, acetylation, sulfation, phosphorylation). We are now at the beginning of a new era using human and microbial whole-genome sequencing to make significant healthcare decisions as to risk, stratification of patients, diagnosis, treatments, and outcomes. Are we as clinicians, scientists, and educators prepared to expand our scope of practice, knowledge base, integration into primary health care (medicine, pharmacy, nursing, and allied health science professions), and clinical approaches to craniofacial-oral-dental health care? The time is now. PMID:24799423

  20. The evolutionary ecology of individual phenotypic plasticity in wild populations

    Microsoft Academic Search

    D. H. NUSSEY; A. J. WILSON; J. E. BROMMER

    2007-01-01

    The ability of individual organisms to alter morphological and life-history traits in response to the conditions they experience is an example of phenotypic plasticity which is fundamental to any population's ability to deal with short- term environmental change. We currently know little about the prevalence, and evolutionary and ecological causes and consequences of variation in life history plasticity in the

  1. Selection for phenotypic plasticity in Rana sylvatica tadpoles

    Microsoft Academic Search

    JOSH VAN BUSKIRK; Rick A. Relyea

    1998-01-01

    The hypothesis that phenotypic plasticity is an adaptation to environmental variation rests on the two assumptions that plasticity improves the performance of individuals that possess it, and that it evolved in response to selection imposed in heterogeneous environments. The first assumption has been upheld by studies showing the beneficial nature of plasticity. The second assumption is diYcult to test since

  2. A Simple Screen to Identify Promoters Conferring High Levels of Phenotypic Noise

    Microsoft Academic Search

    Nikki E. Freed; Olin K. Silander; Bärbel Stecher; Alex Böhm; Wolf-Dietrich Hardt; Martin Ackermann

    2008-01-01

    Genetically identical populations of unicellular organisms often show marked variation in some phenotypic traits. To investigate the molecular causes and possible biological functions of this phenotypic noise, it would be useful to have a method to identify genes whose expression varies stochastically on a certain time scale. Here, we developed such a method and used it for identifying genes with

  3. Phenomics: the systematic study of phenotypes on a genome-wide scale

    Microsoft Academic Search

    R. M. Bilder; F. W. Sabb; T. D. Cannon; E. D. London; J. D. Jentsch; D. Stott Parker; R. A. Poldrack; C. EVANSa; N. B. FREIMERa

    2009-01-01

    Phenomics is an emerging transdiscipline dedicated to the systematic study of phenotypes on a genome-wide scale. New methods for high-throughput genotyping have changed the priority for biomedical research to phenotyping, but the human phenome is vast and its dimensionality remains unknown. Phenomics research strategies capable of linking genetic variation to public health concerns need to prioritize development of mechanistic frameworks

  4. EHR Big Data Deep Phenotyping

    PubMed Central

    Lenert, L.; Lopez-Campos, G.

    2014-01-01

    Summary Objectives Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support the definition of deep phenotypes in medical records. Methods As the vast stores of genomic information increase with next generation sequencing, the importance of deep phenotyping increases. The growth of genomic data and adoption of Electronic Health Records (EHR) in medicine provides a unique opportunity to integrate phenotype and genotype data into medical records. The method by which collections of clinical findings and other health related data are leveraged to form meaningful phenotypes is an active area of research. Longitudinal data stored in EHRs provide a wealth of information that can be used to construct phenotypes of patients. We focus on a practical problem around data integration for deep phenotype identification within EHR data. The use of big data approaches are described that enable scalable markup of EHR events that can be used for semantic and temporal similarity analysis to support the identification of phenotype and genotype relationships. Conclusions Stead and colleagues’ 2005 concept of using light standards to increase the productivity of software systems by riding on the wave of hardware/processing power is described as a harbinger for designing future healthcare systems. The big data solution, using flexible markup, provides a route to improved utilization of processing power for organizing patient records in genotype and phenotype research. PMID:25123744

  5. Pseudomonas Aeruginosa Resistance Phenotypes and Phenotypic Highlighting Methods

    PubMed Central

    B?L??OIU, MARIA; B?L??OIU, A.T.; M?NESCU, RODICA; AVRAMESCU, CARMEN; IONETE, OANA

    2014-01-01

    Pseudomonas aeruginosa genus bacteria are well known for their increased drug resistance (phenotypic ang genotypic resistance). The most important resistance mechanisms are: enzyme production, reduction of pore expression, reduction of the external membrane proteins expression, efflux systems, topoisomerase mutations. These mechanisms often accumulate and lead to multidrug ressitance strains emergence. The most frequent acquired resistance mechanisms are betalactamase-type enzyme production (ESBLs, AmpC, carbapenemases), which determine variable phenotypes of betalactamines resistance, phenotypes which are associated with aminoglycosides and quinolones resistance. The nonenzymatic drug resistance mechanisms are caused by efflux systems, pore reduction and penicillin-binding proteins (PBP) modification, which are often associated to other resistance mechanisms. Phenotypic methods used for testing these mechanisms are based on highlighting these phenotypes using Kirby Bauer antibiogram, clinical breakpoints, and “cut off” values recommended by EUCAST 2013 standard, version 3.1. PMID:25729587

  6. Pseudomonas aeruginosa resistance phenotypes and phenotypic highlighting methods.

    PubMed

    B?l??oiu, Maria; B?l??oiu, A T; M?nescu, Rodica; Avramescu, Carmen; Ionete, Oana

    2014-01-01

    Pseudomonas aeruginosa genus bacteria are well known for their increased drug resistance (phenotypic ang genotypic resistance). The most important resistance mechanisms are: enzyme production, reduction of pore expression, reduction of the external membrane proteins expression, efflux systems, topoisomerase mutations. These mechanisms often accumulate and lead to multidrug ressitance strains emergence. The most frequent acquired resistance mechanisms are betalactamase-type enzyme production (ESBLs, AmpC, carbapenemases), which determine variable phenotypes of betalactamines resistance, phenotypes which are associated with aminoglycosides and quinolones resistance. The nonenzymatic drug resistance mechanisms are caused by efflux systems, pore reduction and penicillin-binding proteins (PBP) modification, which are often associated to other resistance mechanisms. Phenotypic methods used for testing these mechanisms are based on highlighting these phenotypes using Kirby Bauer antibiogram, clinical breakpoints, and "cut off" values recommended by EUCAST 2013 standard, version 3.1. PMID:25729587

  7. Genomic selection using beef commercial carcass phenotypes.

    PubMed

    Todd, D L; Roughsedge, T; Woolliams, J A

    2014-03-01

    In this study, an industry terminal breeding goal was used in a deterministic simulation, using selection index methodology, to predict genetic gain in a beef population modelled on the UK pedigree Limousin, when using genomic selection (GS) and incorporating phenotype information from novel commercial carcass traits. The effect of genotype-environment interaction was investigated by including the model variations of the genetic correlation between purebred and commercial cross-bred performance (?X). Three genomic scenarios were considered: (1) genomic breeding values (GBV)+estimated breeding values (EBV) for existing selection traits; (2) GBV for three novel commercial carcass traits+EBV in existing traits; and (3) GBV for novel and existing traits plus EBV for existing traits. Each of the three scenarios was simulated for a range of training population (TP) sizes and with three values of ?X. Scenarios 2 and 3 predicted substantially higher percentage increases over current selection than Scenario 1. A TP of 2000 sires, each with 20 commercial progeny with carcass phenotypes, and assuming a ?X of 0.7, is predicted to increase gain by 40% over current selection in Scenario 3. The percentage increase in gain over current selection increased with decreasing ?X; however, the effect of varying ?X was reduced at high TP sizes for Scenarios 2 and 3. A further non-genomic scenario (4) was considered simulating a conventional population-wide progeny test using EBV only. With 20 commercial cross-bred progenies per sire, similar gain was predicted to Scenario 3 with TP=5000 and ?X=1.0. The range of increases in genetic gain predicted for terminal traits when using GS are of similar magnitude to those observed after the implementation of BLUP technology in the United Kingdom. It is concluded that implementation of GS in a terminal sire breeding goal, using purebred phenotypes alone, will be sub-optimal compared with the inclusion of novel commercial carcass phenotypes in genomic evaluations. PMID:24345570

  8. Patterns of genetic variation and covariation in ejaculate traits reveal potential evolutionary constraints in guppies

    PubMed Central

    Evans, J P

    2011-01-01

    Ejaculates comprise multiple and potentially interacting traits that determine male fertility and sperm competitiveness. Consequently, selection on these traits is likely to be intense, but the efficacy of selection will depend critically on patterns of genetic variation and covariation underlying their expression. In this study, I provide a prospective quantitative genetic analysis of ejaculate traits in the guppy Poecilia reticulata, a highly promiscuous livebearing fish. I used a standard paternal half-sibling breeding design to characterize patterns of genetic (co)variation in components of sperm length and in vitro sperm performance. All traits exhibited high levels of phenotypic and additive genetic variation, and in several cases, patterns of genetic variation was consistent with Y-linkage. There were also highly significant negative genetic correlations between the various measures of sperm length and sperm performance. In particular, the length of the sperm's midpiece was strongly, negatively and genetically correlated with sperm's swimming velocity—an important determinant of sperm competitiveness in this and other species. Other components of sperm length, including the flagellum and head, were independently and negatively genetically correlated with the proportion of live sperm in the ejaculate (sperm viability). Whether these relationships represent evolutionary trade-offs depends on the precise relationships between these traits and competitive fertilization rates, which have yet to be fully resolved in this (and indeed most) species. Nevertheless, these prospective analyses point to potential constraints on ejaculate evolution and may explain the high level of phenotypic variability in ejaculate traits in this species. PMID:20959863

  9. Connectomic intermediate phenotypes for psychiatric disorders.

    PubMed

    Fornito, Alex; Bullmore, Edward T

    2012-01-01

    Psychiatric disorders are phenotypically heterogeneous entities with a complex genetic basis. To mitigate this complexity, many investigators study so-called intermediate phenotypes (IPs) that putatively provide a more direct index of the physiological effects of candidate genetic risk variants than overt psychiatric syndromes. Magnetic resonance imaging (MRI) is a particularly popular technique for measuring such phenotypes because it allows interrogation of diverse aspects of brain structure and function in vivo. Much of this work however, has focused on relatively simple measures that quantify variations in the physiology or tissue integrity of specific brain regions in isolation, contradicting an emerging consensus that most major psychiatric disorders do not arise from isolated dysfunction in one or a few brain regions, but rather from disturbed interactions within and between distributed neural circuits; i.e., they are disorders of brain connectivity. The recent proliferation of new MRI techniques for comprehensively mapping the entire connectivity architecture of the brain, termed the human connectome, has provided a rich repertoire of tools for understanding how genetic variants implicated in mental disorder impact distinct neural circuits. In this article, we review research using these connectomic techniques to understand how genetic variation influences the connectivity and topology of human brain networks. We highlight recent evidence from twin and imaging genetics studies suggesting that the penetrance of candidate risk variants for mental illness, such as those in SLC6A4, MAOA, ZNF804A, and APOE, may be higher for IPs characterized at the level of distributed neural systems than at the level of spatially localized brain regions. The findings indicate that imaging connectomics provides a powerful framework for understanding how genetic risk for psychiatric disease is expressed through altered structure and function of the human connectome. PMID:22529823

  10. The Broad Autism Phenotype Questionnaire

    ERIC Educational Resources Information Center

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  11. Untangling asthma phenotypes and endotypes.

    PubMed

    Agache, I; Akdis, C; Jutel, M; Virchow, J C

    2012-07-01

    Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice. PMID:22594878

  12. Childhood asthma-predictive phenotype.

    PubMed

    Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

    2014-01-01

    Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. PMID:25439355

  13. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    SciTech Connect

    Wang, Daniel [Iowa State University; Phan, Ngoc [Iowa State University; Isely, Christopher [Iowa State University; Bruene, Lucas [Iowa State University; Bratlie, Kaitlin M [Ames Laboratory

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (?600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  14. Body size phenotypes are heritable and mediate fecundity but not fitness in the lepidopteran frugivore, Cydia pomonella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The inheritance and functional roles of quantitative traits are central concerns of evolutionary ecology. We report two sets of experiments that investigated the heritability and reproductive consequences of body size phenotypes in a globally distributed lepidopteran frugivore, Cydia pomonella (L.)....

  15. Biolog Phenotype Microarrays for phenotypic characterization of microbial cells.

    PubMed

    Mackie, Amanda M; Hassan, Karl A; Paulsen, Ian T; Tetu, Sasha G

    2014-01-01

    Biolog Phenotype MicroArrays for microorganisms provide a high-throughput method for the global analysis of microbial growth phenotypes. Using a colorimetric reaction that is indicative of respiration, these microplate assays measure the response of an individual strain or microbial community to a large and diverse range of nutrients and chemicals. Phenotype MicroArrays have been used to study gene function and to improve genome annotation in single microorganisms and for physiological profiling of bacterial communities. The microplate system can be used to obtain a comprehensive overview of metabolic capability, or it can be tailored, through the use of subsets of plates, to address specific research needs. PMID:24515365

  16. Scaling and shear transformations capture beak shape variation in Darwin’s finches

    PubMed Central

    Campàs, O.; Mallarino, R.; Herrel, A.; Abzhanov, A.; Brenner, M. P.

    2010-01-01

    Evolution by natural selection has resulted in a remarkable diversity of organism morphologies that has long fascinated scientists and served to establish the first relations among species. Despite the essential role of morphology as a phenotype of species, there is not yet a formal, mathematical scheme to quantify morphological phenotype and relate it to both the genotype and the underlying developmental genetics. Herein we demonstrate that the morphological diversity in the beaks of Darwin’s Finches is quantitatively accounted for by the mathematical group of affine transformations. Specifically, we show that all beak shapes of Ground Finches (genus Geospiza) are related by scaling transformations (a subgroup of the affine group), and the same relationship holds true for all the beak shapes of Tree, Cocos, and Warbler Finches (three distinct genera). This analysis shows that the beak shapes within each of these groups differ only by their scales, such as length and depth, which are genetically controlled by Bmp4 and Calmodulin. By measuring Bmp4 expression in the beak primordia of the species in the genus Geospiza, we provide a quantitative map between beak morphology and the expression levels of Bmp4. The complete morphological variation within the beaks of Darwin’s finches can be explained by extending the scaling transformations to the entire affine group, by including shear transformations. Altogether our results suggest that the mathematical theory of groups can help decode morphological variation, and points to a potentially hierarchical structure of morphological diversity and the underlying developmental processes. PMID:20160106

  17. Scaling and shear transformations capture beak shape variation in Darwin's finches.

    PubMed

    Campàs, O; Mallarino, R; Herrel, A; Abzhanov, A; Brenner, M P

    2010-02-23

    Evolution by natural selection has resulted in a remarkable diversity of organism morphologies that has long fascinated scientists and served to establish the first relations among species. Despite the essential role of morphology as a phenotype of species, there is not yet a formal, mathematical scheme to quantify morphological phenotype and relate it to both the genotype and the underlying developmental genetics. Herein we demonstrate that the morphological diversity in the beaks of Darwin's Finches is quantitatively accounted for by the mathematical group of affine transformations. Specifically, we show that all beak shapes of Ground Finches (genus Geospiza) are related by scaling transformations (a subgroup of the affine group), and the same relationship holds true for all the beak shapes of Tree, Cocos, and Warbler Finches (three distinct genera). This analysis shows that the beak shapes within each of these groups differ only by their scales, such as length and depth, which are genetically controlled by Bmp4 and Calmodulin. By measuring Bmp4 expression in the beak primordia of the species in the genus Geospiza, we provide a quantitative map between beak morphology and the expression levels of Bmp4. The complete morphological variation within the beaks of Darwin's finches can be explained by extending the scaling transformations to the entire affine group, by including shear transformations. Altogether our results suggest that the mathematical theory of groups can help decode morphological variation, and points to a potentially hierarchical structure of morphological diversity and the underlying developmental processes. PMID:20160106

  18. QUANTITATIVE TRAIT LOCUS ANALYSIS AND METABOLIC PATHWAYS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The development of molecular markers for crop plants has enabled research on the genetic basis of quantitative traits. However, despite more than a decade of these studies, called quantitative trait locus (QTL) analyses, the molecular basis for variation in most agronomic traits is still largely unk...

  19. Shared spatial effects on quantitative genetic parameters: accounting for spatial autocorrelation and home range overlap reduces estimates of heritability in wild red deer.

    PubMed

    Stopher, Katie V; Walling, Craig A; Morris, Alison; Guinness, Fiona E; Clutton-Brock, Tim H; Pemberton, Josephine M; Nussey, Daniel H

    2012-08-01

    Social structure, limited dispersal, and spatial heterogeneity in resources are ubiquitous in wild vertebrate populations. As a result, relatives share environments as well as genes, and environmental and genetic sources of similarity between individuals are potentially confounded. Quantitative genetic studies in the wild therefore typically account for easily captured shared environmental effects (e.g., parent, nest, or region). Fine-scale spatial effects are likely to be just as important in wild vertebrates, but have been largely ignored. We used data from wild red deer to build "animal models" to estimate additive genetic variance and heritability in four female traits (spring and rut home range size, offspring birth weight, and lifetime breeding success). We then, separately, incorporated spatial autocorrelation and a matrix of home range overlap into these models to estimate the effect of location or shared habitat on phenotypic variation. These terms explained a substantial amount of variation in all traits and their inclusion resulted in reductions in heritability estimates, up to an order of magnitude up for home range size. Our results highlight the potential of multiple covariance matrices to dissect environmental, social, and genetic contributions to phenotypic variation, and the importance of considering fine-scale spatial processes in quantitative genetic studies. PMID:22834741

  20. SHARED SPATIAL EFFECTS ON QUANTITATIVE GENETIC PARAMETERS: ACCOUNTING FOR SPATIAL AUTOCORRELATION AND HOME RANGE OVERLAP REDUCES ESTIMATES OF HERITABILITY IN WILD RED DEER

    PubMed Central

    Stopher, Katie V; Walling, Craig A; Morris, Alison; Guinness, Fiona E; Clutton-Brock, Tim H; Pemberton, Josephine M; Nussey, Daniel H

    2012-01-01

    Social structure, limited dispersal, and spatial heterogeneity in resources are ubiquitous in wild vertebrate populations. As a result, relatives share environments as well as genes, and environmental and genetic sources of similarity between individuals are potentially confounded. Quantitative genetic studies in the wild therefore typically account for easily captured shared environmental effects (e.g., parent, nest, or region). Fine-scale spatial effects are likely to be just as important in wild vertebrates, but have been largely ignored. We used data from wild red deer to build “animal models” to estimate additive genetic variance and heritability in four female traits (spring and rut home range size, offspring birth weight, and lifetime breeding success). We then, separately, incorporated spatial autocorrelation and a matrix of home range overlap into these models to estimate the effect of location or shared habitat on phenotypic variation. These terms explained a substantial amount of variation in all traits and their inclusion resulted in reductions in heritability estimates, up to an order of magnitude up for home range size. Our results highlight the potential of multiple covariance matrices to dissect environmental, social, and genetic contributions to phenotypic variation, and the importance of considering fine-scale spatial processes in quantitative genetic studies. PMID:22834741

  1. A multivariate regression approach to association analysis of a quantitative trait network

    Microsoft Academic Search

    Seyoung Kim; Kyung-ah Sohn; Eric P. Xing

    2009-01-01

    Motivation: Many complex disease syndromes such as asthma consist of a large number of highly related, rather than independent, clinical phenotypes, raising a new technical challenge in identifying genetic variations associated simultaneously with correlated traits. Although a causal genetic variation may influence a group of highly correlated traits jointly, most of the previous association analyses considered each phenotype separately, or

  2. Plant Phenotype Characterization System

    SciTech Connect

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  3. Macropinosome quantitation assay

    PubMed Central

    Wang, Jack T.H.; Teasdale, Rohan D.; Liebl, David

    2014-01-01

    In contrast to phagocytosis, macropinocytosis is not directly initiated by interactions between cell surface receptors and cargo ligands, but is a result of constitutive membrane ruffling driven by dynamic remodelling of cortical actin cytoskeleton in response to stimulation of growth factor receptors. Wang et al. (2010) [13] developed a reliable assay that allows quantitative assessment of the efficiency and kinetics of macropinosome biogenesis and/or maturation in cells where the function of a targeted protein has been perturbed by pharmacological inhibitors or by knock-down or knock-out approaches. In this manuscript we describe a modified quantitative protocol to measure the rate and volume of fluid phase uptake in adherent cells. This assay:•uses fluorescent dextran, microscopy and semi-automated image analysis;•allows quantitation of macropinosomes within large numbers of individual cells;•can be applied also to non-homogenous cell populations including transiently transfected cell monolayers. We present the background necessary to consider when customising this protocol for application to new cell types or experimental variations.

  4. Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines.

    PubMed

    Huang, Wen; Massouras, Andreas; Inoue, Yutaka; Peiffer, Jason; Ràmia, Miquel; Tarone, Aaron M; Turlapati, Lavanya; Zichner, Thomas; Zhu, Dianhui; Lyman, Richard F; Magwire, Michael M; Blankenburg, Kerstin; Carbone, Mary Anna; Chang, Kyle; Ellis, Lisa L; Fernandez, Sonia; Han, Yi; Highnam, Gareth; Hjelmen, Carl E; Jack, John R; Javaid, Mehwish; Jayaseelan, Joy; Kalra, Divya; Lee, Sandy; Lewis, Lora; Munidasa, Mala; Ongeri, Fiona; Patel, Shohba; Perales, Lora; Perez, Agapito; Pu, LingLing; Rollmann, Stephanie M; Ruth, Robert; Saada, Nehad; Warner, Crystal; Williams, Aneisa; Wu, Yuan-Qing; Yamamoto, Akihiko; Zhang, Yiqing; Zhu, Yiming; Anholt, Robert R H; Korbel, Jan O; Mittelman, David; Muzny, Donna M; Gibbs, Richard A; Barbadilla, Antonio; Johnston, J Spencer; Stone, Eric A; Richards, Stephen; Deplancke, Bart; Mackay, Trudy F C

    2014-07-01

    The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available. PMID:24714809

  5. Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines

    PubMed Central

    Huang, Wen; Massouras, Andreas; Inoue, Yutaka; Peiffer, Jason; Ràmia, Miquel; Tarone, Aaron M.; Turlapati, Lavanya; Zichner, Thomas; Zhu, Dianhui; Lyman, Richard F.; Magwire, Michael M.; Blankenburg, Kerstin; Carbone, Mary Anna; Chang, Kyle; Ellis, Lisa L.; Fernandez, Sonia; Han, Yi; Highnam, Gareth; Hjelmen, Carl E.; Jack, John R.; Javaid, Mehwish; Jayaseelan, Joy; Kalra, Divya; Lee, Sandy; Lewis, Lora; Munidasa, Mala; Ongeri, Fiona; Patel, Shohba; Perales, Lora; Perez, Agapito; Pu, LingLing; Rollmann, Stephanie M.; Ruth, Robert; Saada, Nehad; Warner, Crystal; Williams, Aneisa; Wu, Yuan-Qing; Yamamoto, Akihiko; Zhang, Yiqing; Zhu, Yiming; Anholt, Robert R.H.; Korbel, Jan O.; Mittelman, David; Muzny, Donna M.; Gibbs, Richard A.; Barbadilla, Antonio; Johnston, J. Spencer; Stone, Eric A.; Richards, Stephen; Deplancke, Bart; Mackay, Trudy F.C.

    2014-01-01

    The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available. PMID:24714809

  6. Phenotypic and fitness consequences of maternal nest-site choice across multiple early life stages.

    PubMed

    Mitchell, Timothy S; Warner, Daniel A; Janzen, Fredric J

    2013-02-01

    Identifying the relative contributions of genetic, maternal, and environmental factors to phenotypic variation is critical for evaluating the evolutionary potential of fitness-related traits. We employed a novel two-step cross-fostering experiment to quantify the relative contributions of clutch (i.e., maternal identity) and maternally chosen nest sites to phenotypic variation during three early life stages (incubation, hibernation, dispersal) of the painted turtle (Chrysemys picta). By translocating eggs between nests in the field, we demonstrated that both clutch and nest site contribute to phenotypic variation at hatching. Because hatchling C. picta hibernate inside nests, we performed a second cross-foster to decouple the effects of the incubation nest with that of the hibernation nest. Incubation nest explained little variation in phenotypes at spring emergence, but winter nest site was important. We found no evidence that mothers select nest sites specific to reaction norms of their own offspring, suggesting that females may select nest sites with microhabitats that broadly meet similar requirements across the population. After hibernation, we released hatchlings to assess performance and phenotypic selection during dispersal. Hibernation nest site influenced physiological performance during dispersal, and we detected nonlinear selection on hatchling carapace length. Our experiment demonstrates that nest-site choice has substantial effects on phenotypic variation and fitness across multiple early life stages. PMID:23691653

  7. Common Psychiatric Diseases and Human Genetic Variation

    Microsoft Academic Search

    O. Mukherjee; Q. Saleem; M. Purushottam; A. Anand; S. K. Brahmachari; S. Jain

    2002-01-01

    Objective: A better understanding of human genetic variation is important in assessing disease epidemiology and phenotypic variation, and may be critical in evaluating genetic aspects of common genetic diseases, such as schizophrenia, bipolar disease and Parkinson’s. These diseases are particularly difficult to investigate as there are few peripheral markers, and although a genetic aetiology has long been suspected, robust findings

  8. Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

    PubMed Central

    2010-01-01

    Background Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Results Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Conclusion Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. PMID:20707912

  9. Finding Our Way through Phenotypes

    PubMed Central

    Deans, Andrew R.; Lewis, Suzanna E.; Huala, Eva; Anzaldo, Salvatore S.; Ashburner, Michael; Balhoff, James P.; Blackburn, David C.; Blake, Judith A.; Burleigh, J. Gordon; Chanet, Bruno; Cooper, Laurel D.; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T. Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E.; Dumontier, Michel; Franz, Nico M.; Friedrich, Frank; Gkoutos, George V.; Haendel, Melissa; Harmon, Luke J.; Hayamizu, Terry F.; He, Yongqun; Hines, Heather M.; Ibrahim, Nizar; Jackson, Laura M.; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J.; Le Novère, Nicolas; Lundberg, John G.; Macklin, James; Mast, Austin R.; Midford, Peter E.; Mikó, István; Mungall, Christopher J.; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J.; Richter, Stefan; Robinson, Peter N.; Ruttenberg, Alan; Schulz, Katja S.; Segerdell, Erik; Seltmann, Katja C.; Sharkey, Michael J.; Smith, Aaron D.; Smith, Barry; Specht, Chelsea D.; Squires, R. Burke; Thacker, Robert W.; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D.; Vogt, Lars; Wall, Christine E.; Walls, Ramona L.; Westerfeld, Monte; Wharton, Robert A.; Wirkner, Christian S.; Woolley, James B.; Yoder, Matthew J.; Zorn, Aaron M.; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. PMID:25562316

  10. Phenotypic variability in myotonia congenita.

    PubMed

    Colding-Jørgensen, Eskild

    2005-07-01

    Myotonia congenita is a hereditary chloride channel disorder characterized by delayed relaxation of skeletal muscle (myotonia). It is caused by mutations in the skeletal muscle chloride channel gene CLCN1 on chromosome 7. The phenotypic spectrum of myotonia congenita ranges from mild myotonia disclosed only by clinical examination to severe and disabling myotonia with transient weakness and myopathy. The most severe phenotypes are seen in patients with two mutated alleles. Heterozygotes are often asymptomatic but for some mutations heterozygosity is sufficient to cause pronounced myotonia, although without weakness and myopathy. Thus, the phenotype depends on the mutation type to some extent, but this does not explain the fact that severity varies greatly between heterozygous family members and may even vary with time in the individual patient. In this review, existing knowledge about phenotypic variability is summarized, and the possible contributing factors are discussed. PMID:15786415

  11. Finding our way through phenotypes.

    PubMed

    Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. PMID:25562316

  12. Bridging the Gap between Genotype and Phenotype via Network Approaches

    PubMed Central

    Kim, Yoo-Ah; Przytycka, Teresa M.

    2013-01-01

    In the last few years we have witnessed tremendous progress in detecting associations between genetic variations and complex traits. While genome-wide association studies have been able to discover genomic regions that may influence many common human diseases, these discoveries created an urgent need for methods that extend the knowledge of genotype-phenotype relationships to the level of the molecular mechanisms behind them. To address this emerging need, computational approaches increasingly utilize a pathway-centric perspective. These new methods often utilize known or predicted interactions between genes and/or gene products. In this review, we survey recently developed network based methods that attempt to bridge the genotype-phenotype gap. We note that although these methods help narrow the gap between genotype and phenotype relationships, these approaches alone cannot provide the precise details of underlying mechanisms and current research is still far from closing the gap. PMID:23755063

  13. Eco-evolutionary dynamics: disentangling phenotypic, environmental and population fluctuations

    PubMed Central

    Ezard, Thomas H.G.; Côté, Steeve D.; Pelletier, Fanie

    2009-01-01

    Decomposing variation in population growth into contributions from both ecological and evolutionary processes is of fundamental concern, particularly in a world characterized by rapid responses to anthropogenic threats. Although the impact of ecological change on evolutionary response has long been acknowledged, the converse has predominantly been neglected, especially empirically. By applying a recently published conceptual framework, we assess and contrast the relative importance of phenotypic and environmental variability on annual population growth in five ungulate populations. In four of the five populations, the contribution of phenotypic variability was greater than the contribution of environmental variability, although not significantly so. The similarity in the contributions of environment and phenotype suggests that neither is worthy of neglect. Population growth is a consequence of multiple processes, which strengthens arguments advocating integrated approaches to assess how populations respond to their environments. PMID:19414464

  14. Population genetic variation in gene expression is associated withphenotypic variation in Saccharomyces cerevisiae

    SciTech Connect

    Fay, Justin C.; McCullough, Heather L.; Sniegowski, Paul D.; Eisen, Michael B.

    2004-02-25

    The relationship between genetic variation in gene expression and phenotypic variation observable in nature is not well understood. Identifying how many phenotypes are associated with differences in gene expression and how many gene-expression differences are associated with a phenotype is important to understanding the molecular basis and evolution of complex traits. Results: We compared levels of gene expression among nine natural isolates of Saccharomyces cerevisiae grown either in the presence or absence of copper sulfate. Of the nine strains, two show a reduced growth rate and two others are rust colored in the presence of copper sulfate. We identified 633 genes that show significant differences in expression among strains. Of these genes,20 were correlated with resistance to copper sulfate and 24 were correlated with rust coloration. The function of these genes in combination with their expression pattern suggests the presence of both correlative and causative expression differences. But the majority of differentially expressed genes were not correlated with either phenotype and showed the same expression pattern both in the presence and absence of copper sulfate. To determine whether these expression differences may contribute to phenotypic variation under other environmental conditions, we examined one phenotype, freeze tolerance, predicted by the differential expression of the aquaporin gene AQY2. We found freeze tolerance is associated with the expression of AQY2. Conclusions: Gene expression differences provide substantial insight into the molecular basis of naturally occurring traits and can be used to predict environment dependent phenotypic variation.

  15. Single Cell Quantification of Reporter Gene Expression in Live Adult Caenorhabditis elegans Reveals Reproducible Cell-Specific Expression Patterns and Underlying Biological Variation

    PubMed Central

    Mendenhall, Alexander R.; Tedesco, Patricia M.; Sands, Bryan; Johnson, Thomas E.; Brent, Roger

    2015-01-01

    In multicellular organisms such as Caenorhabditis elegans, differences in complex phenotypes such as lifespan correlate with the level of expression of particular engineered reporter genes. In single celled organisms, quantitative understanding of responses to extracellular signals and of cell-to-cell variation in responses has depended on precise measurement of reporter gene expression. Here, we developed microscope-based methods to quantify reporter gene expression in cells of Caenorhabditis elegans with low measurement error. We then quantified expression in strains that carried different configurations of Phsp-16.2-fluorescent-protein reporters, in whole animals, and in all 20 cells of the intestine tissue, which is responsible for most of the fluorescent signal. Some animals bore more recently developed single copy Phsp-16.2 reporters integrated at defined chromosomal sites, others, “classical” multicopy reporter gene arrays integrated at random sites. At the level of whole animals, variation in gene expression was similar: strains with single copy reporters showed the same amount of animal-to-animal variation as strains with multicopy reporters. At the level of cells, in animals with single copy reporters, the pattern of expression in cells within the tissue was highly stereotyped. In animals with multicopy reporters, the cell-specific expression pattern was also stereotyped, but distinct, and somewhat more variable. Our methods are rapid and gentle enough to allow quantification of expression in the same cells of an animal at different times during adult life. They should allow investigators to use changes in reporter expression in single cells in tissues as quantitative phenotypes, and link those to molecular differences. Moreover, by diminishing measurement error, they should make possible dissection of the causes of the remaining, real, variation in expression. Understanding such variation should help reveal its contribution to differences in complex phenotypic outcomes in multicellular organisms. PMID:25946008

  16. Quantitative Analysen

    NASA Astrophysics Data System (ADS)

    Hübner, Philipp

    Der heilige Gral jeglicher Analytik ist, den wahren Wert bestimmen zu können. Dies bedingt quantitative Messmethoden, welche in der molekularen Analytik nun seit einiger Zeit zur Verfügung stehen. Das generelle Problem bei der Quantifizierung ist, dass wir meistens den wahren Wert weder kennen noch bestimmen können! Aus diesem Grund behelfen wir uns mit Annäherungen an den wahren Wert, indem wir aus Laborvergleichsuntersuchungen den Median oder den (robusten) Mittelwert berechnen oder indem wir einen Erwartungswert (expected value) aufgrund der Herstellung des Probenmaterials berechnen. Bei diesen Versuchen der Annäherung an den wahren Wert findet beabsichtigterweise eine Normierung der Analytik statt, entweder nach dem demokratischen Prinzip, dass die Mehrheit bestimmt oder durch zur Verfügungsstellung von geeignetem zertifiziertem Referenzmaterial. Wir müssen uns folglich bewusst sein, dass durch dieses Vorgehen zwar garantiert wird, dass die Mehrheit der Analysenlaboratorien gleich misst, wir jedoch dabei nicht wissen, ob alle gleich gut oder allenfalls gleich schlecht messen.

  17. Symbiotic gut microbes modulate human metabolic phenotypes

    PubMed Central

    Li, Min; Wang, Baohong; Zhang, Menghui; Rantalainen, Mattias; Wang, Shengyue; Zhou, Haokui; Zhang, Yan; Shen, Jian; Pang, Xiaoyan; Zhang, Meiling; Wei, Hua; Chen, Yu; Lu, Haifeng; Zuo, Jian; Su, Mingming; Qiu, Yunping; Jia, Wei; Xiao, Chaoni; Smith, Leon M.; Yang, Shengli; Holmes, Elaine; Tang, Huiru; Zhao, Guoping; Nicholson, Jeremy K.; Li, Lanjuan; Zhao, Liping

    2008-01-01

    Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe–host interactions and the roles of individual bacterial species are obscure. We now demonstrate a“transgenomic” approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial–host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as “the characterization of key functional members of the microbiome that most influence host metabolism and hence health.” For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host–microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions. PMID:18252821

  18. Joint phenotypes, evolutionary conflict and the fundamental theorem of natural selection

    PubMed Central

    Queller, David C.

    2014-01-01

    Multiple organisms can sometimes affect a common phenotype. For example, the portion of a leaf eaten by an insect is a joint phenotype of the plant and insect and the amount of food obtained by an offspring can be a joint trait with its mother. Here, I describe the evolution of joint phenotypes in quantitative genetic terms. A joint phenotype for multiple species evolves as the sum of additive genetic variances in each species, weighted by the selection on each species. Selective conflict between the interactants occurs when selection takes opposite signs on the joint phenotype. The mean fitness of a population changes not just through its own genetic variance but also through the genetic variance for its fitness that resides in other species, an update of Fisher's fundamental theorem of natural selection. Some similar results, using inclusive fitness, apply to within-species interactions. The models provide a framework for understanding evolutionary conflicts at all levels. PMID:24686940

  19. Variation in selection, phenotypic plasticity, and the ecology of sexual

    E-print Network

    Fox, Charles W.

    competition that imposes selection for large male size. However, males are larger than females in the genus to mate with the large male, but the effect is small and appears to be due to scramble competition among competition islikely offset by scramble competition favoring small males when flying (see the discussion

  20. The relationship between isozyme phenotype and morphological variation in Cucurbita

    E-print Network

    Kirkpatrick, Kurt James

    1984-01-01

    -0. 25 2 0. 75-0. 50 2 0. 75 ? 0. 50 2 0. 50-0. 25 2 &0. 95 2 0. 75-0. 50 Linkage Tests Loci = 6 N = 164 Joint Segregation For PGI X PER PGI X GOT PGI X IDH PGI X PGM PGI X MDH PER X GOT PER X IDH PER X PGN PER X MDH GOT X IDH Chi...-continued Joint Segregation For GOT X PGM GOT X MDH IDH X PGM IDH X MDH Chi-square 2. 1519 5. 9553 60. 2990 1. 6796 df 4 0. 75 ? 0. 50 4 0. 25-0. 10 4 &0, 01 4 0. 90-0. 75 0. 24+. 028 testing of the individual variables in a multivariate...

  1. PHENOTYPIC VARIATION WITHIN THE S STRAIN OF ASPERGILLUS FLAVUS

    E-print Network

    Cotty, Peter J.

    document divergence within the S strain isolates of A. flavus. Introduction Aflatoxin contamination of aflatoxin than L strain isolates and can be important contributors to aflatoxin contamination of cottonseed adaptation to the soil environment (Cotty et al., 1994). S strain isolates also vary in ability to produce

  2. Phenotypic and molecular variation in 44 vintage tomato varieties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important goal of tomato breeding is to create varieties that will provide high quality product for fresh consumption. Traits such as lycopene, total soluble solids (TSS), vitamin C and titratable acidity (TA) are major components of fruit flavor and quality. Although several-thousand genotypes a...

  3. Phenotypic and genetic variation in longevity of Polish Landrace sows.

    PubMed

    Sobczy?ska, M; Blicharski, T

    2015-08-01

    The influence of some production traits on the longevity of Polish Landrace sows was evaluated using survival analysis. Estimates of genetic parameters were obtained from the sire and animal components in linear and survival methodologies. Comparison between survival and linear models was based on heritabilities and ranking of estimated breeding values of sires. The same data set, 13 031 sows, was used for both methodologies, even in the presence of censored observations. The effects of herd*year and year*season of the first farrowing had the largest influence on the risk of culling of sows. Sows born in spring season (March-May) had a 24% (p < 0.001) lower hazard for removal than those born in winter (December-February). The age at first farrowing had a small but significant effect on culling: the hazard regression coefficient for this trait was 0.002 per day. Sows that had more piglets born alive and fewer stillborn in the first litter had a decreased risk of being culled. Within a contemporary group, slower growing gilts had decreased removal risk. The relative risk ratios show a marginal decreased rate of culling for sows with backfat thickness between 9.5 and 11 mm compared to the leaner sows. Loin depth had no effect on sow longevity. Heritability estimates ranged from 0.09 to 0.38 depending on the model and type of analysis. In survival analysis, all heritabilities for longevity were higher when analysed with sire models (0.21 and 0.38) compared to animal models (0.09 and 0.16). The use of animal or sire models in the linear analysis gave similar heritability estimates (0.12 and 0.10). Correlations between breeding values for sires were moderate and high, with absolute values from 0.51 to 0.99, depending on the model fitted and methodology. A stronger correlations within methodologies (0.83-0.99) than within models with different methodologies (0.51-0.63) were obtained. PMID:25882772

  4. Phenotypic variation and genetic heterogeneity in Léri-Weill syndrome

    Microsoft Academic Search

    Simone Schiller; Stephanie Spranger; Birgit Schechinger; Maki Fukami; Sabine Merker; Stenvert LS Drop; Jochen Tröger; Hans Knoblauch; Jürgen Kunze; Jörg Seidel; Gudrun A Rappold

    2000-01-01

    Léri-Weill syndrome (LWS) or dyschondrosteosis represents a short stature syndrome characterised by the mesomelic shortening of the forearms and lower legs and by bilateral Madelung deformity of the wrists. Recently, mutations in the pseudoautosomal homeobox gene SHOX have been shown to be causative for this disorder. This gene has previously been described as the short stature gene implicated in Turner

  5. Comparative Interaction Networks: Bridging Genotype to Phenotype

    PubMed Central

    Beltrao, Pedro; Ryan, Colm

    2012-01-01

    Over the past decade, biomedical research has witnessed an exponential increase in the throughput of the characterization of biological systems. Here we review the recent progress in large-scale methods to determine protein–protein, genetic and chemical–genetic interaction networks. We discuss some of the limitations and advantages of the different methods and give examples of how these networks are being used to study the evolutionary process. Comparative studies have revealed that different types of protein–protein interactions diverge at different rates with high conservation of co-complex membership but rapid divergence of more promiscuous interactions like those that mediate post-translational modifications. These evolutionary trends have consistent genetic consequences with highly conserved epistatic interactions within complex subunits but faster divergence of epistatic interactions across complexes or pathways. Finally, we discuss how these evolutionary observations are being used to interpret cross-species chemical-genetic studies and how they might shape therapeutic strategies. Together, these interaction networks offer us an unprecedented level of detail into how genotypes are translated to phenotypes, and we envision that they will be increasingly useful in the interpretation of genetic and phenotypic variation occurring within populations as well as the rational design of combinatorial therapeutics. PMID:22821457

  6. Emergence of phenotype switching through continuous and discontinuous evolutionary transitions.

    PubMed

    Patra, Pintu; Klumpp, Stefan

    2015-01-01

    Bacterial persistence (phenotypic tolerance to antibiotics) provides a prime example of bet-hedging, where normally growing cells generate slow-growing but antibiotic-tolerant persister cells to survive through periods of exposure to antibiotics. The population dynamics of persistence is explained by a phenotype switching mechanism that allows individual cells to switch between these different cellular states with different environmental sensitivities. Here, we perform a theoretical study based on an exact solution for the case of a periodic variation of the environment to address how phenotype switching emerges and under what conditions switching is or is not beneficial for long-time growth. Specifically we report a bifurcation through which a fitness maximum and minimum emerge above a threshold in the duration of exposure to the antibiotic. Only above this threshold, the optimal phenotype switching rates are adjusted to the time scales of the environment, as emphasized by previous theoretical studies, while below the threshold a non-switching population is fitter than a switching one. The bifurcation can be of different type, depending on how the phenotype switching rates are allowed to vary. If the switching rates for both directions of the switch are coupled, the transition is discontinuous and results in evolutionary hysteresis, which we confirm with a stochastic simulation. If the switching rates vary individually, a continuous transition is obtained and no hysteresis is found. We discuss how both scenarios can be linked to changes in the underlying molecular networks. PMID:26020274

  7. Emergence of phenotype switching through continuous and discontinuous evolutionary transitions

    NASA Astrophysics Data System (ADS)

    Patra, Pintu; Klumpp, Stefan

    2015-07-01

    Bacterial persistence (phenotypic tolerance to antibiotics) provides a prime example of bet-hedging, where normally growing cells generate slow-growing but antibiotic-tolerant persister cells to survive through periods of exposure to antibiotics. The population dynamics of persistence is explained by a phenotype switching mechanism that allows individual cells to switch between these different cellular states with different environmental sensitivities. Here, we perform a theoretical study based on an exact solution for the case of a periodic variation of the environment to address how phenotype switching emerges and under what conditions switching is or is not beneficial for long-time growth. Specifically we report a bifurcation through which a fitness maximum and minimum emerge above a threshold in the duration of exposure to the antibiotic. Only above this threshold, the optimal phenotype switching rates are adjusted to the time scales of the environment, as emphasized by previous theoretical studies, while below the threshold a non-switching population is fitter than a switching one. The bifurcation can be of different type, depending on how the phenotype switching rates are allowed to vary. If the switching rates for both directions of the switch are coupled, the transition is discontinuous and results in evolutionary hysteresis, which we confirm with a stochastic simulation. If the switching rates vary individually, a continuous transition is obtained and no hysteresis is found. We discuss how both scenarios can be linked to changes in the underlying molecular networks.

  8. Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing

    SciTech Connect

    Georges, M.; Nielsen, D.; Mackinnon, M.; Mishra, A.; Okimoto, R.; Sargeant, L.S.; Steele, M.R.; Zhao, X. [Genmark Inc., Salt Lake City, UT (United States); Pasquino, A.T. [Virginia Polytechnic Institute and State Univ., Blacksburg, VA (United States)

    1995-02-01

    We have exploited {open_quotes}progeny testing{close_quotes} to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of >150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score {ge} 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding. 44 refs., 4 figs., 3 tabs.

  9. Natural variation in herbivore-induced volatiles in Arabidopsis thaliana.

    PubMed

    Snoeren, Tjeerd A L; Kappers, Iris F; Broekgaarden, Colette; Mumm, Roland; Dicke, Marcel; Bouwmeester, Harro J

    2010-06-01

    To study whether natural variation in Arabidopsis thaliana could be used to dissect the genetic basis of responses to herbivory in terms of induced volatile emissions, nine accessions were characterized upon herbivory by biting-chewing Pieris rapae caterpillars or after treatment with the phytohormone jasmonic acid (JA). Analysis of 73 compounds in the headspace showed quantitative differences in the emission rates of several individual compounds among the accessions. Moreover, variation in the emission of volatile compounds after JA treatment was reflected in the behaviour of the parasitoid Diadegma semiclausum when they were offered the headspace volatiles of several combinations of accessions in two-choice experiments. Accessions also differ in transcript levels of genes that are associated with the emission of plant volatiles. The genes BSMT1 and Cyp72A13 could be connected to the emission of methyl salicylate and (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT), respectively. Overall, Arabidopsis showed interesting phenotypic variations with respect to the volatile blend emitted in response to herbivory that can be exploited to identify genes and alleles that underlie this important plant trait. PMID:20488836

  10. Natural variation in herbivore-induced volatiles in Arabidopsis thaliana

    PubMed Central

    Snoeren, Tjeerd A. L.; Broekgaarden, Colette; Mumm, Roland; Dicke, Marcel; Bouwmeester, Harro J.

    2010-01-01

    To study whether natural variation in Arabidopsis thaliana could be used to dissect the genetic basis of responses to herbivory in terms of induced volatile emissions, nine accessions were characterized upon herbivory by biting-chewing Pieris rapae caterpillars or after treatment with the phytohormone jasmonic acid (JA). Analysis of 73 compounds in the headspace showed quantitative differences in the emission rates of several individual compounds among the accessions. Moreover, variation in the emission of volatile compounds after JA treatment was reflected in the behaviour of the parasitoid Diadegma semiclausum when they were offered the headspace volatiles of several combinations of accessions in two-choice experiments. Accessions also differ in transcript levels of genes that are associated with the emission of plant volatiles. The genes BSMT1 and Cyp72A13 could be connected to the emission of methyl salicylate and (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT), respectively. Overall, Arabidopsis showed interesting phenotypic variations with respect to the volatile blend emitted in response to herbivory that can be exploited to identify genes and alleles that underlie this important plant trait. PMID:20488836

  11. Robust and Sensitive Analysis of Mouse Knockout Phenotypes

    PubMed Central

    Karp, Natasha A.; Melvin, David; Mott, Richard F.

    2012-01-01

    A significant challenge of in-vivo studies is the identification of phenotypes with a method that is robust and reliable. The challenge arises from practical issues that lead to experimental designs which are not ideal. Breeding issues, particularly in the presence of fertility or fecundity problems, frequently lead to data being collected in multiple batches. This problem is acute in high throughput phenotyping programs. In addition, in a high throughput environment operational issues lead to controls not being measured on the same day as knockouts. We highlight how application of traditional methods, such as a Student’s t-Test or a 2-way ANOVA, in these situations give flawed results and should not be used. We explore the use of mixed models using worked examples from Sanger Mouse Genome Project focusing on Dual-Energy X-Ray Absorptiometry data for the analysis of mouse knockout data and compare to a reference range approach. We show that mixed model analysis is more sensitive and less prone to artefacts allowing the discovery of subtle quantitative phenotypes essential for correlating a gene’s function to human disease. We demonstrate how a mixed model approach has the additional advantage of being able to include covariates, such as body weight, to separate effect of genotype from these covariates. This is a particular issue in knockout studies, where body weight is a common phenotype and will enhance the precision of assigning phenotypes and the subsequent selection of lines for secondary phenotyping. The use of mixed models with in-vivo studies has value not only in improving the quality and sensitivity of the data analysis but also ethically as a method suitable for small batches which reduces the breeding burden of a colony. This will reduce the use of animals, increase throughput, and decrease cost whilst improving the quality and depth of knowledge gained. PMID:23300663

  12. Analysis of copy number variations reveals differences among cattle breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in the modern domesticated cattle using array comparative genomic hybridization (array CGH) and quanti...

  13. Identifying the genes underlying quantitative traits: a rationale for the QTN programme

    PubMed Central

    Lee, Young Wha; Gould, Billie A.; Stinchcombe, John R.

    2014-01-01

    The goal of identifying the genes or even nucleotides underlying quantitative and adaptive traits has been characterized as the ‘QTN programme’ and has recently come under severe criticism. Part of the reason for this criticism is that much of the QTN programme has asserted that finding the genes and nucleotides for adaptive and quantitative traits is a fundamental goal, without explaining why it is such a hallowed goal. Here we outline motivations for the QTN programme that offer general insight, regardless of whether QTNs are of large or small effect, and that aid our understanding of the mechanistic dynamics of adaptive evolution. We focus on five areas: (i) vertical integration of insight across different levels of biological organization, (ii) genetic parallelism and the role of pleiotropy in shaping evolutionary dynamics, (iii) understanding the forces maintaining genetic variation in populations, (iv) distinguishing between adaptation from standing variation and new mutation, and (v) the role of genomic architecture in facilitating adaptation. We argue that rather than abandoning the QTN programme, we should refocus our efforts on topics where molecular data will be the most effective for testing hypotheses about phenotypic evolution. PMID:24790125

  14. High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains

    PubMed Central

    Philip, V M; Duvvuru, S; Gomero, B; Ansah, T A; Blaha, C D; Cook, M N; Hamre, K M; Lariviere, W R; Matthews, D B; Mittleman, G; Goldowitz, D; Chesler, E J

    2010-01-01

    Genetic reference populations, particularly the BXD recombinant inbred (BXD RI) strains derived from C57BL/6J and DBA/2J mice, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and covariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict the occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic coregulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium (TMGC) have obtained phenotype data from over 250 measures related to multiple behavioral assays across several batteries: response to, and withdrawal from cocaine, 3,4-methylenedioxymethamphetamine; “ecstasy” (MDMA), morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity and sleep/wake cycles. All traits have been measured in both sexes in approximately 70 strains of the recently expanded panel of BXD RI strains. Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent (N = 37) BXD RI lines was performed. Primary data are publicly available for heritability, sex difference and genetic analyses using the MouseTrack database, and are also available in GeneNetwork.org for quantitative trait locus (QTL) detection and genetic analysis of gene expression. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits. PMID:19958391

  15. Effect of ploidy on stomatal and other quantitative traits in plantain and banana hybrids

    Microsoft Academic Search

    Hilde Vandenhout; Rodomiro Ortiz; Dirk Vuylsteke; Rony Swennen; K. V. Bai

    1995-01-01

    Summary Ploidy polymorphism occurs in the hybrid offspring derived from interspecific crosses between triploid plantains (Musa spp. AAB group) and diploid bananas (M. acuminata). Therefore,Musa breeders are interested in the determination of ploidy and its effects on phenotypic expression of quantitative traits. The aim of this research was to examine the reliability of stomatal and other phenotypic traits to determine

  16. Phenotypic integration in style dimorphic daffodils (Narcissus, Amaryllidaceae) with different pollinators.

    PubMed

    Pérez-Barrales, Rocío; Simón-Porcar, Violeta I; Santos-Gally, Rocío; Arroyo, Juan

    2014-08-19

    Different pollinators can exert different selective pressures on floral traits, depending on how they fit with flowers, which should be reflected in the patterns of variation and covariation of traits. Surprisingly, empirical evidence in support of this view is scarce. Here, we have studied whether the variation observed in floral phenotypic integration and covariation of traits in Narcissus species is associated with different groups of pollinators. Phenotypic integration was studied in two style dimorphic species, both with dimorphic populations mostly visited by long-tongued pollinators (close fit with flowers), and monomorphic populations visited by short-tongued insects (loose fit). For N. papyraceus, the patterns of variation and correlation among traits involved in different functions (attraction and fit with pollinators, transfer of pollen) were compared within and between population types. The genetic diversity of populations was also studied to control for possible effects on phenotypic variation. In both species, populations with long-tongued pollinators displayed greater phenotypic integration than those with short-tongued pollinators. Also, the correlations among traits involved in the same function were stronger than across functions. Furthermore, traits involved in the transfer of pollen were consistently more correlated and less variable than traits involved in the attraction of insects, and these differences were larger in dimorphic than monomorphic populations. In addition, population genetic parameters did not correlate with phenotypic integration or variation. Altogether, our results support current views of the role of pollinators in the evolution of floral integration. PMID:25002703

  17. Harnessing Natural Sequence Variation to Dissect Posttranscriptional Regulatory Networks in Yeast

    PubMed Central

    Fazlollahi, Mina; Lee, Eunjee; Muroff, Ivor; Lu, Xiang-Jun; Gomez-Alcala, Pilar; Causton, Helen C.; Bussemaker, Harmen J.

    2014-01-01

    Understanding how genomic variation influences phenotypic variation through the molecular networks of the cell is one of the central challenges of biology. Transcriptional regulation has received much attention, but equally important is the posttranscriptional regulation of mRNA stability. Here we applied a systems genetics approach to dissect posttranscriptional regulatory networks in the budding yeast Saccharomyces cerevisiae. Quantitative sequence-to-affinity models were built from high-throughput in vivo RNA binding protein (RBP) binding data for 15 yeast RBPs. Integration of these models with genome-wide mRNA expression data allowed us to estimate protein-level RBP regulatory activity for individual segregants from a genetic cross between two yeast strains. Treating these activities as a quantitative trait, we mapped trans-acting loci (activity quantitative trait loci, or aQTLs) that act via posttranscriptional regulation of transcript stability. We predicted and experimentally confirmed that a coding polymorphism at the IRA2 locus modulates Puf4p activity. Our results also indicate that Puf3p activity is modulated by distinct loci, depending on whether it acts via the 5? or the 3? untranslated region of its target mRNAs. Together, our results validate a general strategy for dissecting the connectivity between posttranscriptional regulators and their upstream signaling pathways. PMID:24938291

  18. Individual variation in endocrine systems: moving beyond the `tyranny of the Golden Mean'

    E-print Network

    Review Individual variation in endocrine systems: moving beyond the `tyranny of the Golden Mean and functional significance of phenotypic variation, plasticity and flexibility in endocrine systems, and argue interest to evolutionary biologists (cf. behavioural endocrinology). Keywords: endocrine systems; inter

  19. QDMR: a quantitative method for identification of differentially methylated regions by entropy.

    PubMed

    Zhang, Yan; Liu, Hongbo; Lv, Jie; Xiao, Xue; Zhu, Jiang; Liu, Xiaojuan; Su, Jianzhong; Li, Xia; Wu, Qiong; Wang, Fang; Cui, Ying

    2011-05-01

    DNA methylation plays critical roles in transcriptional regulation and chromatin remodeling. Differentially methylated regions (DMRs) have important implications for development, aging and diseases. Therefore, genome-wide mapping of DMRs across various temporal and spatial methylomes is important in revealing the impact of epigenetic modifications on heritable phenotypic variation. We present a quantitative approach, quantitative differentially methylated regions (QDMRs), to quantify methylation difference and identify DMRs from genome-wide methylation profiles by adapting Shannon entropy. QDMR was applied to synthetic methylation patterns and methylation profiles detected by methylated DNA immunoprecipitation microarray (MeDIP-chip) in human tissues/cells. This approach can give a reasonable quantitative measure of methylation difference across multiple samples. Then DMR threshold was determined from methylation probability model. Using this threshold, QDMR identified 10,651 tissue DMRs which are related to the genes enriched for cell differentiation, including 4740 DMRs not identified by the method developed by Rakyan et al. QDMR can also measure the sample specificity of each DMR. Finally, the application to methylation profiles detected by reduced representation bisulphite sequencing (RRBS) in mouse showed the platform-free and species-free nature of QDMR. This approach provides an effective tool for the high-throughput identification of potential functional regions involved in epigenetic regulation. PMID:21306990

  20. Label-free absolute quantitation of oligosaccharides using multiple reaction monitoring.

    PubMed

    Hong, Qiuting; Ruhaak, L Renee; Totten, Sarah M; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B

    2014-03-01

    An absolute quantitation method for measuring free human milk oligosaccharides (HMOs) in milk samples was developed using multiple reaction monitoring (MRM). To obtain the best sensitivity, the instrument conditions were optimized to reduce the source and postsource fragmentation prior to the quadrupole transmission. Fragmentation spectra of HMOs using collision-induced dissociation were studied to obtain the best characteristic fragments. At least two MRM transitions were used to quantify and identify each structure in the same run. The fragment ions corresponded to the production of singly charged mono-, di-, and trisaccharide fragments. The sensitivity and accuracy of the quantitation using MRM were determined, with the detection limit in the femtomole level and the calibration range spanning over 5 orders of magnitude. Seven commercial HMO standards were used to create calibration curves and were used to determine a universal response for all HMOs. The universal response factor was used to estimate absolute amounts of other structures and the total oligosaccharide content in milk. The quantitation method was applied to 20 human milk samples to determine the variations in HMO concentrations from women classified as secretors and nonsecretors, a phenotype that can be identified by the concentration of 2'-fucosylation in their milk. PMID:24502421

  1. Experimental alteration of DNA methylation affects the phenotypic plasticity of ecologically relevant traits in Arabidopsis thaliana

    Microsoft Academic Search

    Oliver Bossdorf; Davide Arcuri; Christina L. Richards; Massimo Pigliucci

    2010-01-01

    Heritable phenotypic variation in plants can be caused not only by underlying genetic differences, but also by variation in\\u000a epigenetic modifications such as DNA methylation. However, we still know very little about how relevant such epigenetic variation\\u000a is to the ecology and evolution of natural populations. We conducted a greenhouse experiment in which we treated a set of\\u000a natural genotypes

  2. Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.

    PubMed

    Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

    2015-03-01

    The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (? 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database. PMID:24939588

  3. Clustering phenotype populations by genome-wide RNAi and multiparametric imaging

    PubMed Central

    Fuchs, Florian; Pau, Gregoire; Kranz, Dominique; Sklyar, Oleg; Budjan, Christoph; Steinbrink, Sandra; Horn, Thomas; Pedal, Angelika; Huber, Wolfgang; Boutros, Michael

    2010-01-01

    Genetic screens for phenotypic similarity have made key contributions to associating genes with biological processes. With RNA interference (RNAi), highly parallel phenotyping of loss-of-function effects in cells has become feasible. One of the current challenges however is the computational categorization of visual phenotypes and the prediction of biological function and processes. In this study, we describe a combined computational and experimental approach to discover novel gene functions and explore functional relationships. We performed a genome-wide RNAi screen in human cells and used quantitative descriptors derived from high-throughput imaging to generate multiparametric phenotypic profiles. We show that profiles predicted functions of genes by phenotypic similarity. Specifically, we examined several candidates including the largely uncharacterized gene DONSON, which shared phenotype similarity with known factors of DNA damage response (DDR) and genomic integrity. Experimental evidence supports that DONSON is a novel centrosomal protein required for DDR signalling and genomic integrity. Multiparametric phenotyping by automated imaging and computational annotation is a powerful method for functional discovery and mapping the landscape of phenotypic responses to cellular perturbations. PMID:20531400

  4. Co-Regulated Transcriptional Networks Contribute to Natural Genetic Contribute Variation in Drosophila Sleep

    PubMed Central

    Harbison, Susan T.; Carbone, Mary Anna; Ayroles, Julien F.; Stone, Eric A.; Lyman, Richard F.; Mackay, Trudy F. C.

    2009-01-01

    Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes1. Studies in Drosophila2, 3 have revealed molecular pathways4–7 and neural tissues8–10 regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we characterized sleep in 40 wild-derived Drosophila lines and observed abundant genetic variation in sleep architecture. We associated sleep with genome-wide variation in gene expression11 to identify candidate genes. We independently confirmed that molecular polymorphisms in Catecholamines up are associated with variation in sleep; and that P-element mutations in four candidate genes affect sleep and gene expression. Transcripts associated with sleep grouped into biologically plausible genetically correlated transcriptional modules. We confirmed co-regulated gene expression using P-element mutants. Genes associated with sleep duration are evolutionarily conserved. Quantitative genetic analysis of natural phenotypic variation is an efficient method for revealing candidate genes and pathways. PMID:19234472

  5. Quantification of Facial Skeletal Shape Variation in Fibroblast Growth Factor Receptor-Related Craniosynostosis Syndromes

    PubMed Central

    Heuzé, Yann; Martínez-Abadías, Neus; Stella, Jennifer M.; Arnaud, Eric; Collet, Corinne; Fructuoso, Gemma García; Alamar, Mariana; Lo, Lun-Jou; Boyadjiev, Simeon A.; Di Rocco, Federico; Richtsmeier, Joan T.

    2014-01-01

    Background fibroblast growth factor receptor (FGFR) -related craniosynostosis syndromes are caused by many different mutations within FGFR-1, 2, 3, and certain FGFR mutations are associated with more than one clinical syndrome. These syndromes share coronal craniosynostosis and characteristic facial skeletal features, although Apert syndrome (AS) is characterized by a more dysmorphic facial skeleton relative to Crouzon (CS), Muenke (MS), or Pfeiffer syndromes. Methods Here we perform a detailed three-dimensional evaluation of facial skeletal shape in a retrospective sample of cases clinically and/or genetically diagnosed as AS, CS, MS, and Pfeiffer syndrome to quantify variation in facial dysmorphology, precisely identify specific facial features pertaining to these four syndromes, and further elucidate what knowledge of the causative FGFR mutation brings to our understanding of these syndromes. Results Our results confirm a strong correspondence between genotype and facial phenotype for AS and MS with severity of facial dysmorphology diminishing from Apert FGFR2S252W to Apert FGFR2P253R to MS. We show that AS facial shape variation is increased relative to CS, although CS has been shown to be caused by numerous distinct mutations within FGFRs and reduced dosage in ERF. Conclusion Our quantitative analysis of facial phenotypes demonstrate subtle variation within and among craniosynostosis syndromes that might, with further research, provide information about the impact of the mutation on facial skeletal and nonskeletal development. We suggest that precise studies of the phenotypic consequences of genetic mutations at many levels of analysis should accompany next-generation genetic research and that these approaches should proceed cooperatively. PMID:24578066

  6. Chloroplast genome variation in upland and lowland switchgrass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Switchgrass (Panicum virgatum L.) exists at multiple ploidies and two phenotypically distinct ecotypes. To facilitate interploidal comparisons and to understand the extent of sequence variation within existing breeding pools, two complete switchgrass chloroplast genomes were sequenced from individu...

  7. Original article Phenotyping, functional characterization,

    E-print Network

    Paris-Sud XI, Université de

    to mesenteric lymph node cells. The phenotypical characterization by multi-parameter flow cytometry revealed subsets, unique to mucosal surfaces. These include cd T cells, and CD4À CD8À and CD8aa+ T cells. IEL a high frequency of undifferentiated CD4À CD8À T cells in newborn dogs whereas mature CD4+ and CD8

  8. Autism: The Phenotype in Relatives

    Microsoft Academic Search

    A. Bailey; S. Palferman; L. Heavey; A. Le Couteur

    1998-01-01

    There is broad agreement that genetic influences are central in the development of idiopathic autism. Whether relatives manifest genetically related milder phenotypes, and if so how these relate to autism proper, has proved a more contentious issue. A review of the relevant studies indicates that relatives are sometimes affected by difficulties that appear conceptually related to autistic behaviors. These range

  9. How cells change their phenotype

    Microsoft Academic Search

    Jonathan M. W. Slack; David Tosh

    2002-01-01

    Recent attention has focused on the remarkable ability of adult stem cells to produce differentiated cells from embryologically unrelated tissues. This phenomenon is an example of metaplasia and shows that embryological commitments can be reversed or erased under certain circumstances. In some cases, even fully differentiated cells can change their phenotype (transdifferentiation). This review examines recently discovered cases of metaplasia,

  10. Variation ontology: annotator guide

    PubMed Central

    2014-01-01

    Background Systematic representation of information related to genetic and non-genetic variations is required to allow large scale studies, data mining and data integration, and to make it possible to reveal novel relationships between genotype and phenotype. Although lots of variation data is available it is often difficult to use due to lack of systematics. Results A novel ontology, Variation Ontology (VariO http://variationontology.org), was developed for annotation of effects, consequences and mechanisms of variations. In this article instructions are provided on how VariO annotations are made. The major levels for description are the three molecules, namely DNA, RNA and protein. They are further divided to four major sublevels: variation type, function, structure, and property, and further up to eight sublevels. VariO annotation summarizes existing knowledge about a variation and its effects and formalizes it so that computational analyses are efficient. The annotations should be made on as many levels as possible. VariO annotations are made in reference to normal states, which vary for each data item including e.g. reference sequences, wild type properties, and activities. Conclusions Detailed instructions together with examples are provided to indicate how VariO can be used for annotation of variations and their effects. A dedicated tool has been developed for annotation and will be further developed to cover also evidence for the annotations. VariO is suitable for annotation of data in many types of databases. As several different kinds of databases are in a process of adapting VariO annotations it is important to have guidelines to guarantee consistent annotation. PMID:24533660

  11. CAUSAL GRAPHICAL MODELS IN SYSTEMS GENETICS: A UNIFIED FRAMEWORK FOR JOINT INFERENCE OF CAUSAL NETWORK AND GENETIC ARCHITECTURE FOR CORRELATED PHENOTYPES1

    PubMed Central

    Neto, Elias Chaibub; Keller, Mark P.; Attie, Alan D.; Yandell, Brian S.

    2010-01-01

    Causal inference approaches in systems genetics exploit quantitative trait loci (QTL) genotypes to infer causal relationships among phenotypes. The genetic architecture of each phenotype may be complex, and poorly estimated genetic architectures may compromise the inference of causal relationships among phenotypes. Existing methods assume QTLs are known or inferred without regard to the phenotype network structure. In this paper we develop a QTL-driven phenotype network method (QTLnet) to jointly infer a causal phenotype network and associated genetic architecture for sets of correlated phenotypes. Randomization of alleles during meiosis and the unidirectional influence of genotype on phenotype allow the inference of QTLs causal to phenotypes. Causal relationships among phenotypes can be inferred using these QTL nodes, enabling us to distinguish among phenotype networks that would otherwise be distribution equivalent. We jointly model phenotypes and QTLs using homogeneous conditional Gaussian regression models, and we derive a graphical criterion for distribution equivalence. We validate the QTLnet approach in a simulation study. Finally, we illustrate with simulated data and a real example how QTLnet can be used to infer both direct and indirect effects of QTLs and phenotypes that co-map to a genomic region. PMID:21218138

  12. Parallel evolution and inheritance of quantitative traits.

    PubMed

    Schluter, Dolph; Clifford, Elizabeth A; Nemethy, Maria; McKinnon, Jeffrey S

    2004-06-01

    Parallel phenotypic evolution, the independent evolution of the same trait in closely related lineages, is interesting because it tells us about the contribution of natural selection to phenotypic evolution. Haldane and others have proposed that parallel evolution also results from a second process, the similarly biased production of genetic variation in close relatives, an idea that has received few tests. We suggest that influence of shared genetic biases should be detectable by the disproportionate use of the same genes in independent instances of parallel phenotypic evolution. We show how progress in testing this prediction can be made through simple tests of parallel inheritance of genetic differences: similar additive, dominance, and epistasis components in analysis of line means and similar effective numbers of loci. We demonstrate parallel inheritance in two traits, lateral plate number and body shape, in two lineages of threespine stickleback that have adapted independently to freshwater streams on opposite sides of the Pacific Ocean. Notably, reduction of plate number in freshwater involves a substitution at the same major locus in both lineages. Our results represent only a first step in the study of the genetics of parallel phenotypic evolution in sticklebacks. Nevertheless, we have shown how such studies can be employed to test the genetic hypothesis of parallel evolution and how study of parallel evolution might yield insights into the roles of both selection and genetic constraint in phenotypic evolution. PMID:15266380

  13. Genetic Basis of Variation in Morphological and Life-History Traits

    E-print Network

    Funk, W. Chris

    Genetic Basis of Variation in Morphological and Life-History Traits of a Wild Population of Pink-mail: wcfunk@mail.utexas.edu. Abstract Understanding the genetic basis of phenotypic variation is essential for predicting the direction and rate of phenotypic evolution. We estimated heritabilities and genetic

  14. INTRASPECIFIC VARIATION IN A PREDATOR AFFECTS COMMUNITY STRUCTURE AND CASCADING TROPHIC INTERACTIONS

    Microsoft Academic Search

    David M. Post; Eric P. Palkovacs; Erika G. Schielke; Stanley I. Dodson

    2008-01-01

    Intraspecific phenotypic variation in ecologically important traits is widespread and important for evolutionary processes, but its effects on community and ecosystem processes are poorly understood. We use life history differences among populations of alewives, Alosa pseudoharengus, to test the effects of intraspecific phenotypic variation in a predator on pelagic zooplankton community structure and the strength of cascading trophic interactions. We

  15. QUANTITATIVE GENETICS OF PLASTRON SHAPE IN SLIDER TURTLES (TRACHEMYS SCRIPTA)

    Microsoft Academic Search

    Erin M. Myers; Fredric J. Janzen; Dean C. Adams; John K. Tucker

    2006-01-01

    Shape variation is widespread in nature and embodies both a response to and a source for evolution and natural selection. To detect patterns of shape evolution, one must assess the quantitative genetic underpinnings of shape variation as well as the selective environment that the organisms have experienced. Here we used geometric morphometrics to assess variation in plastron shell shape in

  16. Transition from an M1 to a mixed neuroinflammatory phenotype increases amyloid deposition in APP/PS1 transgenic mice

    PubMed Central

    2014-01-01

    Background The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer’s disease, yet the impact of these phenotypes on amyloid-beta (A?) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces A?, but long-term studies have not been performed that track the neuroinflammatory phenotype. Methods Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a bilateral intracranial injection of adeno-associated viral (AAV) vectors expressing IFN? or green fluorescent protein in the frontal cortex and hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFN? protein levels and biochemical levels of A?. The neuroinflammatory phenotype was determined through quantitative PCR. Microglia, astrocytes, and A? levels were assessed with immunohistochemistry. Results AAV expressing IFN? induced an M1 neuroinflammatory phenotype at 4 months and a mixed phenotype along with an increase in A? at 6 months. Microglial staining was increased at 6 months and astrocyte staining was decreased at 4 and 6 months in mice receiving AAV expressing IFN?. Conclusions Expression of IFN? through AAV successfully induced an M1 phenotype at 4 months that transitioned to a mixed phenotype by 6 months. This transition also appeared with an increase in amyloid burden suggesting that a mixed phenotype, or enhanced expression of M2a and M2c markers, could contribute to increasing amyloid burden and disease progression. PMID:25062954

  17. Applying Quantitative Genetic Methods to Primate Social Behavior

    PubMed Central

    Brent, Lauren J. N.

    2013-01-01

    Increasingly, behavioral ecologists have applied quantitative genetic methods to investigate the evolution of behaviors in wild animal populations. The promise of quantitative genetics in unmanaged populations opens the door for simultaneous analysis of inheritance, phenotypic plasticity, and patterns of selection on behavioral phenotypes all within the same study. In this article, we describe how quantitative genetic techniques provide studies of the evolution of behavior with information that is unique and valuable. We outline technical obstacles for applying quantitative genetic techniques that are of particular relevance to studies of behavior in primates, especially those living in noncaptive populations, e.g., the need for pedigree information, non-Gaussian phenotypes, and demonstrate how many of these barriers are now surmountable. We illustrate this by applying recent quantitative genetic methods to spatial proximity data, a simple and widely collected primate social behavior, from adult rhesus macaques on Cayo Santiago. Our analysis shows that proximity measures are consistent across repeated measurements on individuals (repeatable) and that kin have similar mean measurements (heritable). Quantitative genetics may hold lessons of considerable importance for studies of primate behavior, even those without a specific genetic focus. PMID:24659839

  18. Applying Quantitative Genetic Methods to Primate Social Behavior.

    PubMed

    Blomquist, Gregory E; Brent, Lauren J N

    2014-02-01

    Increasingly, behavioral ecologists have applied quantitative genetic methods to investigate the evolution of behaviors in wild animal populations. The promise of quantitative genetics in unmanaged populations opens the door for simultaneous analysis of inheritance, phenotypic plasticity, and patterns of selection on behavioral phenotypes all within the same study. In this article, we describe how quantitative genetic techniques provide studies of the evolution of behavior with information that is unique and valuable. We outline technical obstacles for applying quantitative genetic techniques that are of particular relevance to studies of behavior in primates, especially those living in noncaptive populations, e.g., the need for pedigree information, non-Gaussian phenotypes, and demonstrate how many of these barriers are now surmountable. We illustrate this by applying recent quantitative genetic methods to spatial proximity data, a simple and widely collected primate social behavior, from adult rhesus macaques on Cayo Santiago. Our analysis shows that proximity measures are consistent across repeated measurements on individuals (repeatable) and that kin have similar mean measurements (heritable). Quantitative genetics may hold lessons of considerable importance for studies of primate behavior, even those without a specific genetic focus. PMID:24659839

  19. Application of an Effective Statistical Technique for an Accurate and Powerful Mining of Quantitative Trait Loci for Rice Aroma Trait.

    PubMed

    Golestan Hashemi, Farahnaz Sadat; Rafii, Mohd Y; Ismail, Mohd Razi; Mohamed, Mahmud Tengku Muda; Rahim, Harun A; Latif, Mohammad Abdul; Aslani, Farzad

    2015-01-01

    When a phenotype of interest is associated with an external/internal covariate, covariate inclusion in quantitative trait loci (QTL) analyses can diminish residual variation and subsequently enhance the ability of QTL detection. In the in vitro synthesis of 2-acetyl-1-pyrroline (2AP), the main fragrance compound in rice, the thermal processing during the Maillard-type reaction between proline and carbohydrate reduction produces a roasted, popcorn-like aroma. Hence, for the first time, we included the proline amino acid, an important precursor of 2AP, as a covariate in our QTL mapping analyses to precisely explore the genetic factors affecting natural variation for rice scent. Consequently, two QTLs were traced on chromosomes 4 and 8. They explained from 20% to 49% of the total aroma phenotypic variance. Additionally, by saturating the interval harboring the major QTL using gene-based primers, a putative allele of fgr (major genetic determinant of fragrance) was mapped in the QTL on the 8th chromosome in the interval RM223-SCU015RM (1.63 cM). These loci supported previous studies of different accessions. Such QTLs can be widely used by breeders in crop improvement programs and for further fine mapping. Moreover, no previous studies and findings were found on simultaneous assessment of the relationship among 2AP, proline and fragrance QTLs. Therefore, our findings can help further our understanding of the metabolomic and genetic basis of 2AP biosynthesis in aromatic rice. PMID:26061689

  20. Application of an Effective Statistical Technique for an Accurate and Powerful Mining of Quantitative Trait Loci for Rice Aroma Trait

    PubMed Central

    Golestan Hashemi, Farahnaz Sadat; Rafii, Mohd Y.; Ismail, Mohd Razi; Mohamed, Mahmud Tengku Muda; Rahim, Harun A.; Latif, Mohammad Abdul; Aslani, Farzad

    2015-01-01

    When a phenotype of interest is associated with an external/internal covariate, covariate inclusion in quantitative trait loci (QTL) analyses can diminish residual variation and subsequently enhance the ability of QTL detection. In the in vitro synthesis of 2-acetyl-1-pyrroline (2AP), the main fragrance compound in rice, the thermal processing during the Maillard-type reaction between proline and carbohydrate reduction produces a roasted, popcorn-like aroma. Hence, for the first time, we included the proline amino acid, an important precursor of 2AP, as a covariate in our QTL mapping analyses to precisely explore the genetic factors affecting natural variation for rice scent. Consequently, two QTLs were traced on chromosomes 4 and 8. They explained from 20% to 49% of the total aroma phenotypic variance. Additionally, by saturating the interval harboring the major QTL using gene-based primers, a putative allele of fgr (major genetic determinant of fragrance) was mapped in the QTL on the 8th chromosome in the interval RM223-SCU015RM (1.63 cM). These loci supported previous studies of different accessions. Such QTLs can be widely used by breeders in crop improvement programs and for further fine mapping. Moreover, no previous studies and findings were found on simultaneous assessment of the relationship among 2AP, proline and fragrance QTLs. Therefore, our findings can help further our understanding of the metabolomic and genetic basis of 2AP biosynthesis in aromatic rice. PMID:26061689

  1. Multi-system Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

    PubMed Central

    Fears, Scott C.; Service, Susan K.; Kremeyer, Barbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Franco, Juliana; Lopez, Maria C.; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier; Glahn, David C.; Ospina-Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

    2014-01-01

    IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), yet its pathogenesis remains poorly understood. A focus on measuring multi-system quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that impact on BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomic phenotypes that appear heritable and associated with severe bipolar disorder (BP-I), and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN Multi-generational pedigree study in two closely related, genetically isolated populations: the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). PARTICIPANTS 738 individuals, all from CVCR and ANT pedigrees, of whom 181 are affected with BP-I. MAIN OUTCOME MEASURE Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) phenotypes. RESULTS Seventy-five percent (126) of the phenotypes investigated were significantly heritable, and 31% (53) were associated with BP-I. About 1/4 of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions, and volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE This is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I-association within families that is consistent with expectations from case-control studies. Together these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder. PMID:24522887

  2. Applying Label-Free Quantitation to Top Down Proteomics

    PubMed Central

    2015-01-01

    With the prospect of resolving whole protein molecules into their myriad proteoforms on a proteomic scale, the question of their quantitative analysis in discovery mode comes to the fore. Here, we demonstrate a robust pipeline for the identification and stringent scoring of abundance changes of whole protein forms <30 kDa in a complex system. The input is ?100–400 ?g of total protein for each biological replicate, and the outputs are graphical displays depicting statistical confidence metrics for each proteoform (i.e., a volcano plot and representations of the technical and biological variation). A key part of the pipeline is the hierarchical linear model that is tailored to the original design of the study. Here, we apply this new pipeline to measure the proteoform-level effects of deleting a histone deacetylase (rpd3) in S. cerevisiae. Over 100 proteoform changes were detected above a 5% false positive threshold in WT vs the ?rpd3 mutant, including the validating observation of hyperacetylation of histone H4 and both H2B isoforms. Ultimately, this approach to label-free top down proteomics in discovery mode is a critical technical advance for testing the hypothesis that whole proteoforms can link more tightly to complex phenotypes in cell and disease biology than do peptides created in shotgun proteomics. PMID:24807621

  3. Quantitative Genetics, Pleiotropy, and Morphological Integration in the Dentition of Papio hamadryas

    PubMed Central

    Mahaney, Michael C.

    2012-01-01

    Variation in