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1

Quantitative variation and phenotypic correlations in banana and plantain  

Microsoft Academic Search

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

Rodomiro Ortiz; Dirk Vuylsteke

1998-01-01

2

Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast  

PubMed Central

Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer, and adaptive evolution in experimental organisms1–9. However, it remains unresolved how aneuploidy impacts gene expression and whether aneuploidy could directly bring phenotypic variation and improved fitness over that of euploid counterparts. In this work, we designed a novel scheme to generate, through random meiotic segregation, 38 stable and fully isogenic aneuploid yeast strains with distinct karyotypes and genome contents between 1N and 3N without involving any genetic selection. Through phenotypic profiling under various growth conditions or in the presence of a panel of chemotherapeutic or antifungal drugs, we found that aneuploid strains exhibited diverse growth phenotypes, and some aneuploid strains grew better than euploid control strains under conditions suboptimal for the latter. Using quantitative mass spectrometry-based proteomics, we show that the levels of protein expression largely scale with chromosome copy numbers, following the same trend observed for the transcriptome. These results provide strong evidence that aneuploidy directly impacts gene expression at both the transcriptome and proteome levels and can generate significant phenotypic variation that could bring about fitness gains under diverse conditions. Our findings suggest that the fitness ranking between euploid and aneuploid cells is context- and karyotype-dependent, providing the basis for the notion that aneuploidy can directly underlie phenotypic evolution and cellular adaptation.

Pavelka, Norman; Rancati, Giulia; Zhu, Jin; Bradford, William D.; Saraf, Anita; Florens, Laurence; Sanderson, Brian W.; Hattem, Gaye L.; Li, Rong

2010-01-01

3

Phenotypic Variation in Plants  

NSDL National Science Digital Library

This resource is a detailed manual of protocols and instructional information for carrying out an undergraduate laboratory exercise in ecology and evolutionary biolog. Students examine the causes of phenotypic variation in Brassica rapa. This exercise provides an excellent example of potential factors associated with the causes of phenotypic variation for lower division undergraduates, but could also be expanded upon to allow unique scientific inquiry in labs for upper-division undergrads. It includes student outlines, instructor's notes, and suggested questions for laboratory reports.

Lawrence Blumer (Morehouse College;)

1997-01-01

4

Understanding quantitative genetic variation.  

PubMed

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. What kind of QTL do we expect to find and what can our observations of QTL tell us about how organisms evolve? The key to understanding the evolutionary significance of QTL is to understand the nature of inherited variation, not in the immediate mechanistic sense of how genes influence phenotype, but, rather, to know what evolutionary forces maintain genetic variability. PMID:11823787

Barton, N H; Keightley, P D

2002-01-01

5

[Phenotypic variation in ALS].  

PubMed

Making a diagnosis of typical amyotrophic lateral sclerosis (ALS) is not a tough job, but when it comes to atypical forms of motor neuron disease (MND) which are not uncommon in clinical setting, we may have some difficulty to diagnose ALS/MND. There is striking phenotypic variation in sporadic ALS/MND, such as frail arm syndrome (brachial amyotrophic diplegia), pseudopolyneuritic form, hemiplegic type, ALS/MND with markedly extended involvement beyond the motor system, and MND with basophilic inclusion bodies. These variations must be recognized if physicians are to tailor advice on disease progression, prognosis, drug therapy, and care to the needs of the individual. Clinical trials of new therapeutic agents have been performed, on the assumption that patients with ALS/MND have the same underlying etiology, addressing the heterogeneous population of the patients under a single diagnostic category. This can be detrimental to the well-being of the individual, because clinical heterogeneity may mask drug effects in clinical trials. The attempt to categorize subgroups based on the clinical and pathological backgrounds within the spectrum of ALS/MND may be a critical step in facilitating clinical research in ALS/MND. Definition of clinicopathologic syndromes in patients with ALS/MND is an important challenging task that cannot be ignored. PMID:17432191

Sasaki, Shoichi

2006-11-01

6

Identical mutations and phenotypic variation  

Microsoft Academic Search

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

Ulrich Wolf

1997-01-01

7

Geographical variation in selection, from phenotypes to molecules.  

PubMed

Molecular technologies now allow researchers to isolate quantitative trait loci (QTLs) and measure patterns of gene sequence variation within chromosomal regions containing important polymorphisms. I develop a simulation model to investigate gene sequence evolution within genomic regions that harbor QTLs. The QTLs influence a trait experiencing geographical variation in selection, which is common in nature and produces obvious differentiation at the phenotypic level. Counter to expectations, the simulations suggest that selection can substantially affect quantitative genetic variation without altering the amount and pattern of molecular variation at sites closely linked to the QTLs. Even with large samples of gene sequences, the likelihood of rejecting neutrality is often low. The exception is situations where strong selection is combined with low migration among demes, conditions that may be common in many plant species. The results have implications for gene sequence surveys and, perhaps more generally, for interpreting the apparently weak connection between levels of molecular and quantitative trait variation within species. PMID:16670992

Kelly, John K

2006-04-01

8

Developmental interactions and the constituents of quantitative variation.  

PubMed

Development is the process by which genotypes are transformed into phenotypes. Consequently, development determines the relationship between allelic and phenotypic variation in a population and, therefore, the patterns of quantitative genetic variation and covariation of traits. Understanding the developmental basis of quantitative traits may lead to insights into the origin and evolution of quantitative genetic variation, the evolutionary fate of populations, and, more generally, the relationship between development and evolution. Herein, we assume a hierarchical, modular structure of trait development and consider how epigenetic interactions among modules during ontogeny affect patterns of phenotypic and genetic variation. We explore two developmental models, one in which the epigenetic interactions between modules result in additive effects on character expression and a second model in which these epigenetic interactions produce nonadditive effects. Using a phenotype landscape approach, we show how changes in the developmental processes underlying phenotypic expression can alter the magnitude and pattern of quantitative genetic variation. Additive epigenetic effects influence genetic variances and covariances, but allow trait means to evolve independently of the genetic variances and covariances, so that phenotypic evolution can proceed without changing the genetic covariance structure that determines future evolutionary response. Nonadditive epigenetic effects, however, can lead to evolution of genetic variances and covariances as the mean phenotype evolves. Our model suggests that an understanding of multivariate evolution can be considerably enriched by knowledge of the mechanistic basis of character development. PMID:11308082

Wolf, J B; Frankino, W A; Agrawal, A F; Brodie, E D; Moore, A J

2001-02-01

9

Integrating binary traits with quantitative phenotypes for association mapping of multivariate phenotypes.  

PubMed

Clinical binary end-point traits are often governed by quantitative precursors. Hence it may be a prudent strategy to analyze a clinical end-point trait by considering a multivariate phenotype vector, possibly including both quantitative and qualitative phenotypes. A major statistical challenge lies in integrating the constituent phenotypes into a reduced univariate phenotype for association analyses. We assess the performances of certain reduced phenotypes using analysis of variance and a model-free quantile-based approach. We find that analysis of variance is more powerful than the quantile-based approach in detecting association, particularly for rare variants. We also find that using a principal component of the quantitative phenotypes and the residual of a logistic regression of the binary phenotype on the quantitative phenotypes may be an optimal method for integrating a binary phenotype with quantitative phenotypes to define a reduced univariate phenotype. PMID:22373144

Mukhopadhyay, Indranil; Saha, Sujayam; Ghosh, Saurabh

2011-01-01

10

Quantitative analysis of interindividual variation of glutathione S-transferase expression in human pancreas and the ambiguity of correlating genotype with phenotype.  

PubMed

Analysis of glutathione S-transferases (GSTs) of the alpha, mu, and pi classes by reverse-phase high-performance liquid chromatography and electrospray-ionization mass spectrometry in 43 samples of normal human pancreas demonstrated a wide variation in expression of subunits P1, A1, A2, A4, M1, M2, and M3 and the presence of a novel form designated GST "A5." GSTA2 consisted of three forms that were differentially expressed between individuals in a manner consistent with allelic polymorphism at the hGSTA2 locus. Expression, in terms of microg GST subunit/mg cytosolic protein, varied by 6-15-fold for subunits P1, A2, and M3 and 17-30-fold in the case of GSTs A1 and M2. Less consistently expressed were GSTs M1a, M1b, A4, and A5. Among these, GSTM1 expression (excluding M1-null samples) varied 12-fold between samples, whereas GST A4 and A5 expression varied approximately 50-100-fold between samples, well beyond the range of other subunits, suggesting that their expression is highly inducible. Linear correlations (P < 0.001-0.003) existed between levels of the most consistently expressed GST, GSTP1, and total GSTs, GSTA2 and M3, and in GSTM1-positive samples, between GSTM1, M3, and P1. The correlation between GST subunits P1 and M3 was bimodal according to M1 genotype, reflecting the presence of the regulatory element in hGSTM3*B that is linked with the hGSTM1*A genotype. It is concluded that although a degree of regulation of expression of GSTs occurs in human pancreas, the variability of phenotype is high and might obscure the effects of genetic polymorphisms on individual cancer susceptibility. Interindividual variation of GST expression is, therefore, a factor that should be taken account of in epidemiological studies. PMID:10676639

Coles, B F; Anderson, K E; Doerge, D R; Churchwell, M I; Lang, N P; Kadlubar, F F

2000-02-01

11

What Role Does Heritable Epigenetic Variation Play in Phenotypic Evolution?  

NSDL National Science Digital Library

To explore the potential evolutionary relevance of heritable epigenetic variation, the National Evolutionary Synthesis Center recently hosted a catalysis meeting that brought together molecular epigeneticists, experimental evolutionary ecologists, and theoretical population and quantitative geneticists working across a wide variety of systems. The group discussed the methods available to investigate epigenetic variation and epigenetic inheritance, and how to evaluate their importance for phenotypic evolution. We found that understanding the relevance of epigenetic effects in phenotypic evolution will require clearly delineating epigenetics within existing terminology and expanding research efforts into ecologically relevant circumstances across model and nonmodel organisms. In addition, a critical component of understanding epigenetics will be the development of new and current statistical approaches and expansion of quantitative and population genetic theory. Although the importance of heritable epigenetic effects on evolution is still under discussion, investigating them in the context of a multidisciplinary approach could transform the field.

Christina Richards (University of South Florida;Department of Integrative Biology)

2010-03-01

12

Quantitative phenotypic analysis of multistress response in Zygosaccharomyces rouxii complex.  

PubMed

Zygosaccharomyces rouxii complex comprises three yeasts clusters sourced from sugar- and salt-rich environments: haploid Zygosaccharomyces rouxii, diploid Zygosaccharomyces sapae and allodiploid/aneuploid strains of uncertain taxonomic affiliations. These yeasts have been characterized with respect to gene copy number variation, karyotype variability and change in ploidy, but functional diversity in stress responses has not been explored yet. Here, we quantitatively analysed the stress response variation in seven strains of the Z. rouxii complex by modelling growth variables via model and model-free fitting methods. Based on the spline fit as most reliable modelling method, we resolved different interstrain responses to 15 environmental perturbations. Compared with Z. rouxii CBS 732(T) and Z. sapae strains ABT301(T) and ABT601, allodiploid strain ATCC 42981 and aneuploid strains CBS 4837 and CBS 4838 displayed higher multistress resistance and better performance in glycerol respiration even in the presence of copper. ?-based logarithmic phenotypic index highlighted that ABT601 is a slow-growing strain insensitive to stress, whereas ABT301(T) grows fast on rich medium and is sensitive to suboptimal conditions. Overall, the differences in stress response could imply different adaptation mechanisms to sugar- and salt-rich niches. The obtained phenotypic profiling contributes to provide quantitative insights for elucidating the adaptive mechanisms to stress in halo- and osmo-tolerant Zygosaccharomyces yeasts. PMID:24533625

Solieri, Lisa; Dakal, Tikam C; Bicciato, Silvio

2014-06-01

13

Quantitative Analysis of Interindividual Variation of Glutathione S-Transferase Expression in Human Pancreas and the Ambiguity of Correlating Genotype with Phenotype1  

Microsoft Academic Search

Analysis of glutathione S-transferases (GSTs) of the alpha, mu, and pi classes by reverse-phase high-performance liquid chromatography and electrospray-ionization mass spectrometry in 43 samples of normal hu- man pancreas demonstrated a wide variation in expression of subunits P1, A1, A2, A4, M1, M2, and M3 and the presence of a novel form designated GST \\

Brian F. Coles; Kristin E. Anderson; Daniel R. Doerge; Mona I. Churchwell; Nicholas P. Lang; Fred F. Kadlubar

14

Hemophilia B is a quasi-quantitative condition with certain mutations showing phenotypic plasticity.  

PubMed

Hemophilia B has been considered as a classical monogenic disorder with complete penetrance. Here, we observed that its allelic spectrum encompasses mutations that show least phenotypic variation as well as those showing phenotypic plasticity, thereby establishing hemophilia B as a quasi-quantitative condition with variable expressivity. Thus, we relocate it from simple monogenic diseases with complete penetrance into a space that marks the conceptual continuum of Mendelian to complex diseases. By computational analysis, we show that mutations showing phenotypic variation were characterized by relatively less conserved mutant sites and more tolerated conservative substitutions. We also demonstrate that consideration of continuous phenotypes renders quantitative rigor for interrogation and hence higher predictive value while analyzing for differential properties than classifications based on clinical end points. Certain mutations have been consistently reported to cause mild phenotype, calling for a check in indiscriminate termination of fetuses following prenatal diagnosis. PMID:19699296

Chavali, Sreenivas; Ghosh, Saurabh; Bharadwaj, Dwaipayan

2009-12-01

15

Linking Post-Translational Modifications and Variation of Phenotypic Traits*  

PubMed Central

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.

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

2013-01-01

16

Quantitative phenotyping via deep barcode sequencing.  

PubMed

Next-generation DNA sequencing technologies have revolutionized diverse genomics applications, including de novo genome sequencing, SNP detection, chromatin immunoprecipitation, and transcriptome analysis. Here we apply deep sequencing to genome-scale fitness profiling to evaluate yeast strain collections in parallel. This method, Barcode analysis by Sequencing, or "Bar-seq," outperforms the current benchmark barcode microarray assay in terms of both dynamic range and throughput. When applied to a complex chemogenomic assay, Bar-seq quantitatively identifies drug targets, with performance superior to the benchmark microarray assay. We also show that Bar-seq is well-suited for a multiplex format. We completely re-sequenced and re-annotated the yeast deletion collection using deep sequencing, found that approximately 20% of the barcodes and common priming sequences varied from expectation, and used this revised list of barcode sequences to improve data quality. Together, this new assay and analysis routine provide a deep-sequencing-based toolkit for identifying gene-environment interactions on a genome-wide scale. PMID:19622793

Smith, Andrew M; Heisler, Lawrence E; Mellor, Joseph; Kaper, Fiona; Thompson, Michael J; Chee, Mark; Roth, Frederick P; Giaever, Guri; Nislow, Corey

2009-10-01

17

Drosophila bristles and the nature of quantitative genetic variation.  

PubMed

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

Mackay, Trudy F; Lyman, Richard F

2005-07-29

18

Intra familial phenotypical variations in adrenoleukodystrophy.  

PubMed

Adrenoleukodystrophy (ALD) is an X-linked recessively inherited peroxisomal disorder, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. It has a wide phenotypical variability ranging from symptomatic childhood cerebral form to the asymptomatic with biochemical defects only; sometimes within the same family. We report a family of three siblings diagnosed with ALD confirmed with the mutations in ABCD1 gene having phenotypical variability ranging from pure adrenal insufficiency to progressive neurodegeneration in the same family. The mother was identified as the carrier and maternal uncle was diagnosed with Adrenomyeloneuropathy. We discuss the variable presentation in our family and the possible causes of phenotypical variability. PMID:20228476

Gosalakkal, Jayaprakash; Balky, Anand Prasad

2010-01-01

19

Sexual selection and temporal phenotypic variation in a damselfly population.  

PubMed

Temporal variation in selection can be generated by temporal variation in either the fitness surface or phenotypic distributions around a static fitness surface, or both concurrently. Here, we use within- and between-generation sampling of fitness surfaces and phenotypic distributions over 2 years to investigate the causes of temporal variation in the form of sexual selection on body size in the damselfly Enallagma aspersum. Within a year, when the average female body size differed substantially from the average male body size, male body size experienced directional selection. In contrast, when male and female size distributions overlapped, male body size experienced stabilizing selection when variances in body size were large, but no appreciable selection when the variances in body size were small. The causes of temporal variation in the form of selection can only be inferred by accounting for changes in both the fitness surface and changes in the distribution of phenotypes. PMID:21569154

Steele, D B; Siepielski, A M; McPeek, M A

2011-07-01

20

Quantitative genetic variation in Daphnia: temporal changes in genetic architecture.  

PubMed

Nonadditive genetic variation and genetic disequilibrium are two important factors that influence the evolutionary trajectory of natural populations. We assayed quantitative genetic variation in a temporary-pond-dwelling population of Daphnia pulex over a full season to examine the role of nonadditive genetic variation and genetic disequilibrium in determining the short-term evolutionary trajectory of a cyclic parthenogen. Quantitative traits were influenced by three factors: (1) clonal selection significantly changed the population mean phenotype during the course of the growing season; (2) sexual reproduction and recombination led to significant changes in life-history trait means and the levels of expressed genetic variation, implying the presence of substantial nonadditive genetic variation and genetic disequilibrium; and (3) Egg-bank effects were found to be an important component of the realized year-to-year change. Additionally, we examined the impact of genetic disequilibria induced by clonal selection on the genetic (co)variance structure with a common principal components model. Clonal selection caused significant changes in the (co)variance structure that were eliminated by a single bout of random mating, suggesting that a build-up of disequilibria was the primary source of changes in the (co)variance structure. The results of this study highlight the complexity of natural selection operating on populations that undergo alternating phases of sexual and asexual reproduction. PMID:11108579

Pfrender, M E; Lynch, M

2000-10-01

21

Extensive Phenotypic Variation in Early Flowering Mutants of Arabidopsis1  

PubMed Central

Flowering time, the major regulatory transition of plant sequential development, is modulated by multiple endogenous and environmental factors. By phenotypic profiling of 80 early flowering mutants of Arabidopsis, we examine how mutational reduction of floral repression is associated with changes in phenotypic plasticity and stability. Flowering time measurements in mutants reveal deviations from the linear relationship between the number of leaves and number of days to bolting described for natural accessions and late flowering mutants. The deviations correspond to relative early bolting and relative late bolting phenotypes. Only a minority of mutants presents no detectable phenotypic variation. Mutants are characterized by a broad release of morphological pleiotropy under short days, with leaf characters being most variable. They also exhibit changes in phenotypic plasticity across environments for florigenic-related responses, including the reaction to light and dark, photoperiodic behavior, and Suc sensitivity. Morphological pleiotropy and plasticity modifications are differentially distributed among mutants, resulting in a large diversity of multiple phenotypic changes. The pleiotropic effects observed may indicate that floral repression defects are linked to global developmental perturbations. This first, to our knowledge, extensive characterization of phenotypic variation in early flowering mutants correlates with the reports that most factors recruited in floral repression at the molecular genetic level correspond to ubiquitous regulators. We discuss the importance of functional ubiquity for floral repression with respect to robustness and flexibility of network biological systems.

Pouteau, Sylvie; Ferret, Valerie; Gaudin, Valerie; Lefebvre, Delphine; Sabar, Mohammed; Zhao, Gengchun; Prunus, Franck

2004-01-01

22

Extensive phenotypic variation in early flowering mutants of Arabidopsis.  

PubMed

Flowering time, the major regulatory transition of plant sequential development, is modulated by multiple endogenous and environmental factors. By phenotypic profiling of 80 early flowering mutants of Arabidopsis, we examine how mutational reduction of floral repression is associated with changes in phenotypic plasticity and stability. Flowering time measurements in mutants reveal deviations from the linear relationship between the number of leaves and number of days to bolting described for natural accessions and late flowering mutants. The deviations correspond to relative early bolting and relative late bolting phenotypes. Only a minority of mutants presents no detectable phenotypic variation. Mutants are characterized by a broad release of morphological pleiotropy under short days, with leaf characters being most variable. They also exhibit changes in phenotypic plasticity across environments for florigenic-related responses, including the reaction to light and dark, photoperiodic behavior, and Suc sensitivity. Morphological pleiotropy and plasticity modifications are differentially distributed among mutants, resulting in a large diversity of multiple phenotypic changes. The pleiotropic effects observed may indicate that floral repression defects are linked to global developmental perturbations. This first, to our knowledge, extensive characterization of phenotypic variation in early flowering mutants correlates with the reports that most factors recruited in floral repression at the molecular genetic level correspond to ubiquitous regulators. We discuss the importance of functional ubiquity for floral repression with respect to robustness and flexibility of network biological systems. PMID:15122022

Pouteau, Sylvie; Ferret, Valérie; Gaudin, Valérie; Lefebvre, Delphine; Sabar, Mohammed; Zhao, Gengchun; Prunus, Franck

2004-05-01

23

Phenotypic variation and diversity among Trichomonas vaginalis isolates and correlation of phenotype with trichomonal virulence determinants.  

PubMed Central

The extent and nature of heterogeneity among representative Trichomonas vaginalis isolates were evaluated by flow cytofluorometry analysis. Monoclonal antibody and monospecific antiserum to an immunodominant trichomonad surface glycoprotein with a molecular weight of 267,000 (267K glycoprotein) were used to evaluate fresh isolates (JHH and RU375) and long-term grown isolates (NYH286, IR78, and JH31A) of T. vaginalis. Isolates NYH286, JH31A, and JHH were made up of heterogeneous staining (positive [pos] phenotype) and nonstaining (negative [neg] phenotype) populations of trichomonads, whereas RU375 and IR78 were all neg phenotype parasites. Flow cytofluorometric patterns of agar clones derived from single organisms of heterogeneous isolates such as NYH286 showed populations which were either homogeneous pos or neg and also showed clones which were heterogeneous in nature containing both phenotypes. Fluorescence-activated cell sorting was also accomplished, and subpopulations of defined pos or neg phenotype were purified. Flow cytofluorometry evaluation of all isolates for an extended period revealed a phenotypic variation among all heterogeneous isolates and also for all clones and subpopulations derived from the heterogeneous isolates. On the other hand, IR78 and RU375 did not undergo phenotypic variation and have remained neg for greater than 4 years. Parasites which were nonreactive with either monoclonal antibody or monospecific antiserum to the 267K glycoprotein in flow cytofluorometry did not possess the antigen on their surface. This was determined by radioimmunoprecipitation assays using extracts of iodinated trichomonads. Finally, neg phenotype parasites yielded enhanced rates of contact-dependent cytotoxicity of host cell monolayers as compared with the pos phenotype trichomonads. Images

Alderete, J F; Kasmala, L; Metcalfe, E; Garza, G E

1986-01-01

24

Phenotypic Variation in Infants, Not Adults, Reflects Genotypic Variation among Chimpanzees and Bonobos  

PubMed Central

Studies comparing phenotypic variation with neutral genetic variation in modern humans have shown that genetic drift is a main factor of evolutionary diversification among populations. The genetic population history of our closest living relatives, the chimpanzees and bonobos, is now equally well documented, but phenotypic variation among these taxa remains relatively unexplored, and phenotype-genotype correlations are not yet documented. Also, while the adult phenotype is typically used as a reference, it remains to be investigated how phenotype-genotye correlations change during development. Here we address these questions by analyzing phenotypic evolutionary and developmental diversification in the species and subspecies of the genus Pan. Our analyses focus on the morphology of the femoral diaphysis, which represents a functionally constrained element of the locomotor system. Results show that during infancy phenotypic distances between taxa are largely congruent with non-coding (neutral) genotypic distances. Later during ontogeny, however, phenotypic distances deviate from genotypic distances, mainly as an effect of heterochronic shifts between taxon-specific developmental programs. Early phenotypic differences between Pan taxa are thus likely brought about by genetic drift while late differences reflect taxon-specific adaptations.

Morimoto, Naoki; Ponce de Leon, Marcia S.; Zollikofer, Christoph P. E.

2014-01-01

25

The genetics of phenotypic plasticity. X. Variation versus uncertainty.  

PubMed

Despite the apparent advantages of adaptive plasticity, it is not common. We examined the effects of variation and uncertainty on selection for plasticity using an individual-based computer simulation model. In the model, the environment consisted of a linear gradient of 50 demes with dispersal occurring either before or after selection. Individuals consisted of multiple loci whose phenotypic expression either are affected (plastic) or are not affected (nonplastic) by the environment. Typically, evolution occurred first as genetic differentiation, which was then replaced by the evolution of adaptive plasticity, opposite to the evolutionary trend that is often assumed. Increasing dispersal rates selected for plasticity, if selection occurred before dispersal. If selection occurred after dispersal, the highest plasticity was at intermediate dispersal rates. Temporal variation in the environment occurring after development, but before selection, favored the evolution of plasticity. With dispersal before selection, such temporal variation resulted in hyperplasticity, with a reaction norm much steeper than the optimum. This effect was enhanced with negative temporal autocorrelation and can be interpreted as representing a form of bet hedging. As the number of nonplastic loci increased, plasticity was disfavored due to an increase in the uncertainty of the genomic environment. This effect was reversed with temporal variation. Thus, variation and uncertainty affect whether or not plasticity is favored with different sources of variation-arising from the amount and timing of dispersal, from temporal variation, and even from the genetic architecture underlying the phenotype-having contrasting, interacting, and at times unexpected effects. PMID:22837824

Scheiner, Samuel M; Holt, Robert D

2012-04-01

26

Phenotypical variation within 22 families with Pompe disease  

PubMed Central

Background Pompe disease has a broad clinical spectrum, in which the phenotype is partially explained by the genotype. The aim of this study was to describe phenotypical variation among siblings with non-classic Pompe disease. We hypothesized that siblings and families with the same genotype share more similar phenotypes than the total population of non-classic Pompe patients, and that this might reveal genotype-phenotype correlations. Methods We identified all Dutch families in which two or three siblings were diagnosed with Pompe disease and described genotype, acid ?-glucosidase activity, age at symptom onset, presenting symptoms, specific clinical features, mobility and ventilator dependency. Results We identified 22 families comprising two or three siblings. All carried the most common mutation c.-32-13 T?>?G in combination with another pathogenic mutation. The median age at symptom onset was 33 years (range 1–62 years). Within sibships symptom onset was either in childhood or in adulthood. The median variation in symptom onset between siblings was nine years (range 0–31 years). Presenting symptoms were similar across siblings in 14 out of 22 families. Limb girdle weakness was most frequently reported. In some families ptosis or bulbar weakness were present in all siblings. A large variation in disease severity (based on wheelchair/ventilator dependency) was observed in 11 families. This variation did not always result from a difference in duration of the disease since a third of the less affected siblings had a longer course of the disease. Enzyme activity could not explain this variation either. In most families male patients were more severely affected. Finally, symptom onset varied substantially in twelve families despite the same GAA genotype. Conclusion In most families with non-classic Pompe disease siblings share a similar phenotype regarding symptom onset, presenting symptoms and specific clinical features. However, in some families the course and severity of disease varied substantially. This phenotypical variation was also observed in families with identical GAA genotypes. The commonalities and differences indicate that besides genotype, other factors such as epigenetic and environmental effects influence the clinical presentation and disease course.

2013-01-01

27

Molecular Biomarkers for Quantitative and Discrete COPD Phenotypes  

PubMed Central

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disorder with complex pathological features and largely unknown etiology. The identification of biomarkers for this disease could aid the development of methods to facilitate earlier diagnosis, the classification of disease subtypes, and provide a means to define therapeutic response. To identify gene expression biomarkers, we completed expression profiling of RNA derived from the lung tissue of 56 subjects with varying degrees of airflow obstruction using the Affymetrix U133 Plus 2.0 array. We applied multiple, independent analytical methods to define biomarkers for either discrete or quantitative disease phenotypes. Analysis of differential expression between cases (n = 15) and controls (n = 18) identified a set of 65 discrete biomarkers. Correlation of gene expression with quantitative measures of airflow obstruction (FEV1%predicted or FEV1/FVC) identified a set of 220 biomarkers. Biomarker genes were enriched in functions related to DNA binding and regulation of transcription. We used this group of biomarkers to predict disease in an unrelated data set, generated from patients with severe emphysema, with 97% accuracy. Our data contribute to the understanding of gene expression changes occurring in the lung tissue of patients with obstructive lung disease and provide additional insight into potential mechanisms involved in the disease process. Furthermore, we present the first gene expression biomarker for COPD validated in an independent data set.

Bhattacharya, Soumyaroop; Srisuma, Sorachai; DeMeo, Dawn L.; Shapiro, Steven D.; Bueno, Raphael; Silverman, Edwin K.; Reilly, John J.; Mariani, Thomas J.

2009-01-01

28

Understanding and using quantitative genetic variation.  

PubMed

Quantitative genetics, or the genetics of complex traits, is the study of those characters which are not affected by the action of just a few major genes. Its basis is in statistical models and methodology, albeit based on many strong assumptions. While these are formally unrealistic, methods work. Analyses using dense molecular markers are greatly increasing information about the architecture of these traits, but while some genes of large effect are found, even many dozens of genes do not explain all the variation. Hence, new methods of prediction of merit in breeding programmes are again based on essentially numerical methods, but incorporating genomic information. Long-term selection responses are revealed in laboratory selection experiments, and prospects for continued genetic improvement are high. There is extensive genetic variation in natural populations, but better estimates of covariances among multiple traits and their relation to fitness are needed. Methods based on summary statistics and predictions rather than at the individual gene level seem likely to prevail for some time yet. PMID:20008387

Hill, William G

2010-01-12

29

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

PubMed Central

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, containing 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. In A. thaliana MAM is responsible for side chain elongation in aliphatic glucosinolates, and the MAM phenotype can be characterized by the ratios of long- to short-chain glucosinolates. A quantitative trait loci (QTL) analysis of glucosinolate ratios in an A. lyrata interpopulation cross found one QTL at MAM. Additional QTL were identified for total indolic glucosinolates and for the ratio of aliphatic to indolic glucosinolates. MAM was then used as the candidate gene for a within-population cosegregation analysis in a natural A. lyrata population from Germany. Extensive variation in microsatellite markers at MAM was found and this variation cosegregated with the same glucosinolate ratios as in the QTL study. The combined results indicate that both between- and within-population genetic variation in the MAM region determines phenotypic variation in glucosinolate side chains in A. lyrata.

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

2006-01-01

30

Phenotypic variation in the plant pathogenic bacterium Acidovorax citrulli.  

PubMed

Acidovorax citrulli causes bacterial fruit blotch (BFB) of cucurbits, a disease that threatens the cucurbit industry worldwide. Despite the economic importance of BFB, little is known about pathogenicity and fitness strategies of the bacterium. We have observed the phenomenon of phenotypic variation in A. citrulli. Here we report the characterization of phenotypic variants (PVs) of two strains, M6 and 7a1, isolated from melon and watermelon, respectively. Phenotypic variation was observed following growth in rich medium, as well as upon isolation of bacteria from inoculated plants or exposure to several stresses, including heat, salt and acidic conditions. When grown on nutrient agar, all PV colonies possessed a translucent appearance, in contrast to parental strain colonies that were opaque. After 72 h, PV colonies were bigger than parental colonies, and had a fuzzy appearance relative to parental strain colonies that are relatively smooth. A. citrulli colonies are generally surrounded by haloes detectable by the naked eye. These haloes are formed by type IV pilus (T4P)-mediated twitching motility that occurs at the edge of the colony. No twitching haloes could be detected around colonies of both M6 and 7a1 PVs, and microscopy observations confirmed that indeed the PVs did not perform twitching motility. In agreement with these results, transmission electron microscopy revealed that M6 and 7a1 PVs do not produce T4P under tested conditions. PVs also differed from their parental strain in swimming motility and biofilm formation, and interestingly, all assessed variants were less virulent than their corresponding parental strains in seed transmission assays. Slight alterations could be detected in some DNA fingerprinting profiles of 7a1 variants relative to the parental strain, while no differences at all could be seen among M6 variants and parental strain, suggesting that, at least in the latter, phenotypic variation is mediated by slight genetic and/or epigenetic alterations. PMID:24023830

Shrestha, Ram Kumar; Rosenberg, Tally; Makarovsky, Daria; Eckshtain-Levi, Noam; Zelinger, Einat; Kopelowitz, June; Sikorski, Johannes; Burdman, Saul

2013-01-01

31

Phenotypic Variation in the Plant Pathogenic Bacterium Acidovorax citrulli  

PubMed Central

Acidovorax citrulli causes bacterial fruit blotch (BFB) of cucurbits, a disease that threatens the cucurbit industry worldwide. Despite the economic importance of BFB, little is known about pathogenicity and fitness strategies of the bacterium. We have observed the phenomenon of phenotypic variation in A. citrulli. Here we report the characterization of phenotypic variants (PVs) of two strains, M6 and 7a1, isolated from melon and watermelon, respectively. Phenotypic variation was observed following growth in rich medium, as well as upon isolation of bacteria from inoculated plants or exposure to several stresses, including heat, salt and acidic conditions. When grown on nutrient agar, all PV colonies possessed a translucent appearance, in contrast to parental strain colonies that were opaque. After 72 h, PV colonies were bigger than parental colonies, and had a fuzzy appearance relative to parental strain colonies that are relatively smooth. A. citrulli colonies are generally surrounded by haloes detectable by the naked eye. These haloes are formed by type IV pilus (T4P)-mediated twitching motility that occurs at the edge of the colony. No twitching haloes could be detected around colonies of both M6 and 7a1 PVs, and microscopy observations confirmed that indeed the PVs did not perform twitching motility. In agreement with these results, transmission electron microscopy revealed that M6 and 7a1 PVs do not produce T4P under tested conditions. PVs also differed from their parental strain in swimming motility and biofilm formation, and interestingly, all assessed variants were less virulent than their corresponding parental strains in seed transmission assays. Slight alterations could be detected in some DNA fingerprinting profiles of 7a1 variants relative to the parental strain, while no differences at all could be seen among M6 variants and parental strain, suggesting that, at least in the latter, phenotypic variation is mediated by slight genetic and/or epigenetic alterations.

Shrestha, Ram Kumar; Rosenberg, Tally; Makarovsky, Daria; Eckshtain-Levi, Noam; Zelinger, Einat; Kopelowitz, June; Sikorski, Johannes; Burdman, Saul

2013-01-01

32

Evolution of adaptive phenotypic variation patterns by direct selection for evolvability.  

PubMed

A basic assumption of the Darwinian theory of evolution is that heritable variation arises randomly. In this context, randomness means that mutations arise irrespective of the current adaptive needs imposed by the environment. It is broadly accepted, however, that phenotypic variation is not uniformly distributed among phenotypic traits, some traits tend to covary, while others vary independently, and again others barely vary at all. Furthermore, it is well established that patterns of trait variation differ among species. Specifically, traits that serve different functions tend to be less correlated, as for instance forelimbs and hind limbs in bats and humans, compared with the limbs of quadrupedal mammals. Recently, a novel class of genetic elements has been identified in mouse gene-mapping studies that modify correlations among quantitative traits. These loci are called relationship loci, or relationship Quantitative Trait Loci (rQTL), and affect trait correlations by changing the expression of the existing genetic variation through gene interaction. Here, we present a population genetic model of how natural selection acts on rQTL. Contrary to the usual neo-Darwinian theory, in this model, new heritable phenotypic variation is produced along the selected dimension in response to directional selection. The results predict that selection on rQTL leads to higher correlations among traits that are simultaneously under directional selection. On the other hand, traits that are not simultaneously under directional selection are predicted to evolve lower correlations. These results and the previously demonstrated existence of rQTL variation, show a mechanism by which natural selection can directly enhance the evolvability of complex organisms along lines of adaptive change. PMID:21106581

Pavlicev, Mihaela; Cheverud, James M; Wagner, Günter P

2011-06-22

33

Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits  

PubMed Central

Genetic variations in metabolism of endocannabinoids and in CNR1 (gene for cannabinoid 1 receptor) are associated with symptom phenotype, colonic transit, and left colon motility in irritable bowel syndrome (IBS). Our aim was to evaluate associations between two variations in CNR1 genotype (rs806378 and [AAT]n triplets) with symptom phenotype, small bowel and colonic transit, and rectal sensations in 455 patients with IBS and 228 healthy controls. Small bowel and colonic transit were measured by scintigraphy, rectal sensation by isobaric distensions. Associations with genotype were assessed by ?2 test (symptom phenotype) and ANCOVA (quantitative traits) based on a dominant genetic model. Significant association of CNR1 rs806378 (but not CNR1 [AAT]n) genotype and symptom phenotype was observed (?2 P = 0.028). There was significant association of CNR1 rs806378 (P = 0.014; CC vs. CT/TT) with colonic transit in IBS-diarrhea (IBS-D) group; the TT group had the fastest colonic transit at 24 and 48 h. There was significant overall association of CNR1 rs806378 with sensation rating of gas (P = 0.025), but not pain; the strongest associations for gas ratings were in IBS-D (P = 0.002) and IBS-alternating (P = 0.025) subgroups. For CNR1 (AAT)n, gene-by-phenotype interactions were observed for colonic transit at 24 (P = 0.06) and 48 h (P = 0.002) and gas (P = 0.046, highest for IBS-D, P = 0.034), but not pain sensation; the strongest association with transit was in controls, not in IBS. These data support the hypothesis that cannabinoid receptors may play a role in control of colonic transit and sensation in humans and deserve further study as potential mediators or therapeutic targets in lower functional gastrointestinal disorders.

Kolar, Gururaj J.; Vazquez-Roque, Maria I.; Carlson, Paula; Burton, Duane D.; Zinsmeister, Alan R.

2013-01-01

34

Genetic Variations Strongly Influence Phenotypic Outcome in the Mouse Retina  

PubMed Central

Variation in genetic background can significantly influence the phenotypic outcome of both disease and non-disease associated traits. Additionally, differences in temporal and strain specific gene expression can also contribute to phenotypes in the mammalian retina. This is the first report of microarray based cross-strain analysis of gene expression in the retina investigating genetic background effects. Microarray analyses were performed on retinas from the following mouse strains: C57BL6/J, AKR/J, CAST/EiJ, and NOD.NON-H2-nb1 at embryonic day 18.5 (E18.5) and postnatal day 30.5 (P30.5). Over 3000 differentially expressed genes were identified between strains and developmental stages. Differential gene expression was confirmed by qRT-PCR, Western blot, and immunohistochemistry. Three major gene networks were identified that function to regulate retinal or photoreceptor development, visual perception, cellular transport, and signal transduction. Many of the genes in these networks are implicated in retinal diseases such as bradyopsia, night-blindness, and cone-rod dystrophy. Our analysis revealed strain specific variations in cone photoreceptor cell patterning and retinal function. This study highlights the substantial impact of genetic background on both development and function of the retina and the level of gene expression differences tolerated for normal retinal function. These strain specific genetic variations may also be present in other tissues. In addition, this study will provide valuable insight for the development of more accurate models for human retinal diseases.

Jelcick, Austin S.; Yuan, Yang; Leehy, Barrett D.; Cox, Lakeisha C.; Silveira, Alexandra C.; Qiu, Fang; Schenk, Sarah; Sachs, Andrew J.; Morrison, Margaux A.; Nystuen, Arne M.; DeAngelis, Margaret M.; Haider, Neena B.

2011-01-01

35

Relationships among strains classified with the ruminant Pasteurella haemolytica-complex using quantitative evaluation of phenotypic data.  

PubMed

The phenotypic relationships among 246 trehalose-negative strains classified under the [Pasteurella] haemolytica-complex in ruminants were investigated by clustering and multidimensional ordinations based upon 79 phenotypic characters. A quantitative evaluation of phenotypic data using a 5-level scoring system is presented permitting a comprehensive utilization of the recorded phenotypic variation among the strains in the analyses. Clustering and ordination analyses display complementary aspects of data which has been clearly demonstrated in this investigation. The main clusters revealed by the numerical techniques could be related to distinctive phenotypic differences and showed an extensive correlation with the recognized biogroups. This classification was based only upon 4 characters (fermentation of L-arabinose, D-sorbitol, glucosides and ornithine decarboxylase). In contrast, there was no obvious interpretation of the clusters formed by using binary scores. Phenotypic subgroups within the recognized biogroups have been described as well as a new, related group of bacteria, tentatively named Bisgaard taxon 36. Quantitative interpretation of phenotypic data seems to represent a promising method for finding relations among affiliated strains of bacteria and to assist in forming hypotheses for subsequent genotypic investigations. PMID:9144907

Angen, O; Aalbaek, B; Falsen, E; Olsen, J E; Bisgaard, M

1997-04-01

36

Phenotypic variation and selective mortality as major drivers of recruitment variability in fishes.  

PubMed

An individual's phenotype will usually influence its probability of survival. However, when evaluating the dynamics of populations, the role of selective mortality is not always clear. Not all mortality is selective, patterns of selective mortality may vary, and it is often unknown how selective mortality compares or interacts with other sources of mortality. As a result, there is seldom a clear expectation for how changes in the phenotypic composition of populations will translate into differences in average survival. We address these issues by evaluating how selective mortality affects recruitment of fish populations. First, we provide a quantitative review of selective mortality. Our results show that most of the mortality during early life is selective, and that variation in phenotypes can have large effects on survival. Next, we describe an analytical framework that accounts for variation in selection, while also describing the amount of selective mortality experienced by different cohorts recruiting to a single population. This framework is based on reconstructing fitness surfaces from phenotypic selection measurements, and can be employed for either single or multiple traits. Finally, we show how this framework can be integrated with models of density-dependent survival to improve our understanding of recruitment variability and population dynamics. PMID:24674603

Johnson, Darren W; Grorud-Colvert, Kirsten; Sponaugle, Su; Semmens, Brice X

2014-06-01

37

PHENOTYPIC VARIATION OF COLONIC MOTOR FUNCTIONS IN CHRONIC CONSTIPATION  

PubMed Central

Background & Aims Colonic motor disturbances in chronic constipation (CC) are heterogeneous and incompletely understood; the relationship between colonic transit and motor activity is unclear. We sought to characterize the phenotypic variability in chronic constipation. Methods Fasting and postprandial colonic tone and phasic activity and pressure–volume relationships were assessed by a barostat manometric assembly in 35 healthy women and 111 women with CC who had normal colon transit (NTC, n=25), slow transit (STC, n=19), and defecatory disorders with normal (DD-normal, n=34) or slow transit (DD-slow, n=33). Logistic regression models assessed whether motor parameters could discriminate among these groups. Among CC, phenotypes were characterized by principal components analysis of these measurements. Results Compared to 10th percentile values in healthy subjects, fasting and/or postprandial colonic tone and/or compliance were reduced in 40% with NTC, 47% with STC, 53% with DD-normal, and 42% with DD-slow transit. Compared to healthy subjects, compliance was reduced (p ? 0.05) in isolated STC and DD but not in NTC. Four principal components accounted for 85% of the total variation among patients; factors 1 and 2 were predominantly weighted by fasting and postprandial colonic phasic activity and tone respectively; factor 3 by postprandial high-amplitude propagated contractions, and factor 4 by postprandial tonic response. Conclusions Fasting and/or postprandial colonic tone are reduced, reflecting motor dysfunctions, even in NTC. Colonic motor assessments allow chronic constipation to be characterized into phenotypes. Further studies are needed to evaluate the relationship between these phenotypes, enteric neuropathology and response to treatment in CC.

Ravi, Karthik; Bharucha, Adil E.; Camilleri, Michael; Rhoten, Deborah; Bakken, Timothy; Zinsmeister, Alan R.

2009-01-01

38

Pregnancy-induced metabolic phenotype variations in maternal plasma.  

PubMed

Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH?), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH? and tryptophan catabolites indicated that the fluctuations of neurotransmitters throughout pregnancy might reveal the metabolic adaption in the maternal body for the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species were also determined and this showed variations in the presence of long-chain acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of acylcarnitines and lysophospholipids to meet the energy demands in pregnant women. To our knowledge, this work is the first report of dynamic metabolic signatures and proposed related metabolic pathways in the maternal plasma for normal pregnancies and provided the basis for time-dependent metabolic trajectory against which disease-related disorders may be contrasted. PMID:24450375

Luan, Hemi; Meng, Nan; Liu, Ping; Feng, Qiang; Lin, Shuhai; Fu, Jin; Davidson, Robert; Chen, Xiaomin; Rao, Weiqiao; Chen, Fang; Jiang, Hui; Xu, Xun; Cai, Zongwei; Wang, Jun

2014-03-01

39

Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans  

PubMed Central

The role of the Alzheimer’s Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome-wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within Alzheimer’s Disease Neuroimaging Initiative. Genome-wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer’s disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials.

Saykin, Andrew J.; Shen, Li; Foroud, Tatiana M.; Potkin, Steven G.; Swaminathan, Shanker; Kim, Sungeun; Risacher, Shannon L.; Nho, Kwangsik; Huentelman, Matthew J.; Craig, David W.; Thompson, Paul M.; Stein, Jason L.; Moore, Jason H.; Farrer, Lindsay A.; Green, Robert C.; Bertram, Lars; Jack, Clifford R.; Weiner, Michael W.

2010-01-01

40

Structural genomic variation in childhood epilepsies with complex phenotypes.  

PubMed

A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. PMID:24281369

Helbig, Ingo; Swinkels, Marielle E M; Aten, Emmelien; Caliebe, Almuth; van 't Slot, Ruben; Boor, Rainer; von Spiczak, Sarah; Muhle, Hiltrud; Jähn, Johanna A; van Binsbergen, Ellen; van Nieuwenhuizen, Onno; Jansen, Floor E; Braun, Kees P J; de Haan, Gerrit-Jan; Tommerup, Niels; Stephani, Ulrich; Hjalgrim, Helle; Poot, Martin; Lindhout, Dick; Brilstra, Eva H; Møller, Rikke S; Koeleman, Bobby Pc

2014-07-01

41

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

PubMed

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

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

2014-07-22

42

Population Structure in Daphnia Obtusa: Quantitative Genetic and Allozymic Variation  

PubMed Central

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.

Spitze, K.

1993-01-01

43

Disentangling the phylogenetic and ecological components of spider phenotypic variation.  

PubMed

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

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

2014-01-01

44

Mutations and quantitative genetic variation: lessons from Drosophila.  

PubMed

A central issue in evolutionary quantitative genetics is to understand how genetic variation for quantitative traits is maintained in natural populations. Estimates of genetic variation and of genetic correlations and pleiotropy among multiple traits, inbreeding depression, mutation rates for fitness and quantitative traits and of the strength and nature of selection are all required to evaluate theoretical models of the maintenance of genetic variation. Studies in Drosophila melanogaster have shown that a substantial fraction of segregating variation for fitness-related traits in Drosophila is due to rare deleterious alleles maintained by mutation-selection balance, with a smaller but significant fraction attributable to intermediate frequency alleles maintained by alleles with antagonistic pleiotropic effects, and late-age-specific effects. However, the nature of segregating variation for traits under stabilizing selection is less clear and requires more detailed knowledge of the loci, mutation rates, allelic effects and frequencies of molecular polymorphisms affecting variation in suites of pleiotropically connected traits. Recent studies in D. melanogaster have revealed unexpectedly complex genetic architectures of many quantitative traits, with large numbers of pleiotropic genes and alleles with sex-, environment- and genetic background-specific effects. Future genome wide association analyses of many quantitative traits on a common panel of fully sequenced Drosophila strains will provide much needed empirical data on the molecular genetic basis of quantitative traits. PMID:20308098

Mackay, Trudy F C

2010-04-27

45

Quantitative Variation, Selection and Inheritance with Fast Plants  

NSDL National Science Digital Library

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.

Program, The W.

46

Quantitative genetic variation in static allometry in the threespine stickleback.  

PubMed

The common pattern of replicated evolution of a consistent shape-environment relationship might reflect selection acting in similar ways within each environment, but divergently among environments. However, phenotypic evolution depends on the availability of additive genetic variation as well as on the direction of selection, implicating a bias in the distribution of genetic variance as a potential contributor to replicated evolution. Allometry, the relationship between shape and size, is a potential source of genetic bias that is poorly understood. The threespine stickleback, Gasterosteus aculeatus, provides an ideal system for exploring the contribution of genetic variance in body shape allometry to evolutionary patterns. The stickleback system comprises marine populations that exhibit limited phenotypic variation, and young freshwater populations which, following independent colonization events, have often evolved similar phenotypes in similar environments. In particular, stickleback diversification has involved changes in both total body size and relative size of body regions (i.e., shape). In a laboratory-reared cohort derived from an oceanic Alaskan population that is phenotypically and genetically representative of the ancestor of the diverse freshwater populations in this region, we determined the phenotypic static allometry, and estimated the additive genetic variation about these population-level allometric functions. We detected significant allometry, with larger fish having relatively smaller heads, a longer base to their second dorsal fin, and longer, shallower caudal peduncles. There was additive genetic variance in body size and in size-independent body shape (i.e., allometric elevation), but typically not in allometric slopes. These results suggest that the parallel evolution of body shape in threespine stickleback is not likely to have been a correlated response to selection on body size, or vice versa. Although allometry is common in fishes, this study highlights the need for additional data on genetic variation in allometric functions to determine how allometry evolves and how it influences phenotypic evolution. PMID:21558260

McGuigan, Katrina; Nishimura, Nicole; Currey, Mark; Hurwit, Dan; Cresko, William A

2010-12-01

47

Quantitative phenotypic and pathway profiling guides rational drug combination strategies  

PubMed Central

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.

Dawson, John C.; Carragher, Neil O.

2014-01-01

48

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

Microsoft Academic Search

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

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

2008-01-01

49

Markov chain Monte Carlo linkage analysis of complex quantitative phenotypes.  

PubMed

We report a Markov chain Monte Carlo analysis of the five simulated quantitative traits in Genetic Analysis Workshop 12 using the Loki software. Our objectives were to determine the efficacy of the Markov chain Monte Carlo method and to test a new scoring technique. Our initial blind analysis, on replicate 42 (the "best replicate") successfully detected four out of the five disease loci and found no false positives. A power analysis shows that the software could usually detect 4 of the 10 trait/gene combinations at an empirical point-wise p-value of 1.5 x 10(-4). PMID:11793758

Hinrichs, A; Reich, T

2001-01-01

50

Molecular and Phenotypic Variation of the Zw Locus Region in Drosophila Melanogaster  

PubMed Central

Restriction map polymorphism in a 13-kb region of the Zw locus in Drosophila melanogaster was investigated for 64 X chromosome lines with seven 6-cutter and ten 4-cutter restriction enzymes. A total of 203 restriction sites were scored, of which 20 were found to be polymorphic. The estimated nucleotide variation for this region for overall data (? = 0.003 and 0.001, and ? = 0.003 and 0.002, for 4-cutter and 6-cutter studies, respectively) was smaller than that reported for most regions studied in D. melanogaster. It was found that the Slow allozyme has a larger nucleotide variation and haplotype diversity than the Fast allozyme. Results suggest the relatively recent divergence of the Fast allozyme from the Slow allozyme. Glucose 6-phosphate dehydrogenase (G6PD) activity was measured as a phenotype of the Zw locus. A significant difference in G6PD activity between allozymes was detected. The between-line effect was highly significant within the Slow allozyme, but was not significant within the Fast allozyme. Although a direct causative link could not be established, these results suggest an association between the amounts of quantitative and molecular genetic variation at the Zw locus region.

Miyashita, N. T.

1990-01-01

51

Quantitative genetic variation: a post-modern view.  

PubMed

It has become commonplace to map individual quantitative trait loci (QTL) in experimental organisms; the means (line-crosses and dense maps of markers) and motivation (the close relationship between continuous physiological traits and common, complex diseases) are self-evident. Progress in mapping human QTL has been more gradual, an inevitable consequence of genetic mapping in a natural population setting. The common objective of these studies has been to understand the molecular mechanisms underlying individual QTL. Recent theoretical and practical advances shift this focus to a more comprehensive or genomic perspective on quantitative variation. Fisher's infinitesimal model of adaptive evolution, which satisfied quantitative geneticists for over 50 years, has been modified in the light of data from QTL mapping experiments in plants and animals. The resulting exponential model provides a pleasing empirical fit to the distribution of QTL effect sizes, predicts that a large amount of quantitative variation will be explained by a limited number of genes and suggests a new mathematical framework for linkage mapping. Molecular analysis of QTL suggests that coding variants (e.g. allozymes) underlie a fraction of quantitative variation and that variants that affect gene expression (expression QTL, eQTL) have a substantial role. This is supported by genomic experiments that combine expression profiling with classical genetic mapping approaches to reveal a remarkable wealth of quantitative heritable variation in the transcriptome and that cis-and trans-acting regulatory factors are organized in networks reflecting pleiotropy. It is hoped that these advances will enhance our understanding of the genetic basis of complex inherited diseases. PMID:14962979

Farrall, Martin

2004-04-01

52

From Genotype to Phenotype: Systems Biology Meets Natural Variation  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. The promise that came with genome sequencing was that we would soon know what genes do. We now have the full genomic sequence of human, chimpanzee, mouse, chicken, dog, worm, fly, rice, and cress, as well as those for a wide variety of other species, and yet we still have a lot of trouble figuring out what genes do. Mapping genes to their function is called the "genotype-to-phenotype problem," where phenotype is whatever is changed in the organism when a gene's function is altered.

Philip N. Benfey (Duke University;Department of Biology; Institute for Genome Sciences and PolicyâÂÂCenter for Systems Biology); Thomas Mitchell-Olds (Duke University;Department of Biology)

2008-04-25

53

Genome-Wide Pathway Association Studies of Multiple Correlated Quantitative Phenotypes Using Principle Component Analyses  

PubMed Central

Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS) approach using principle component analysis(PCA). In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD) at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

Zhang, Feng; Guo, Xiong; Wu, Shixun; Han, Jing; Liu, Yongjun; Shen, Hui; Deng, Hong-Wen

2012-01-01

54

Transgenerational genetic effects on phenotypic variation and disease risk  

Microsoft Academic Search

Traditionally, we understand that individual phenotypes result primarily from inherited genetic variants together with environmental exposures. However, many studies showed that a remarkable variety of factors including environmental agents, parental behaviors, maternal physiology, xenobiotics, nutritional sup- plements and others lead to epigenetic changes that can be transmitted to subsequent generations without continued exposure. Recent discoveries show transgenerational epistasis and transgenerational

Joseph H. Nadeau

2009-01-01

55

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

PubMed Central

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.

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

2010-01-01

56

Quantitative trait loci affecting natural variation in Drosophila longevity.  

PubMed

Limited life span and senescence are universal phenomena, controlled by genetic and environmental factors whose interactions both limit life span and generate variation in life span between individuals, populations and species. To understand the genetic architecture of longevity it is necessary to know what loci affect variation in life span, what are the allelic effects at these loci and what molecular polymorphisms define quantitative trait locus (QTL) alleles. Here, we used quantitative complementation tests to determine whether genes that regulate longevity also contribute to naturally occurring variation in Drosophila life span. Inbred strains derived from a natural population were crossed to stocks containing null mutations (m) or deficiencies (Df) uncovering the candidate genes, maintained over a Balancer (Bal) chromosome. We measured the life span of the resulting F(1) genotypes, +(i)/m (Df) and +(i)/Bal, where +(i) denotes one of the i natural alleles. Failure of the QTL alleles to complement the candidate gene mutation is indicated by a significant cross (mutant versus wild-type allele of the candidate gene) by inbred line interaction term from analysis of variance of life span. Failure to complement indicates a genetic interaction between the candidate gene allele and the naturally occurring life span QTL, and implicates the candidate gene as potential cause of variation in longevity. Of the 16 candidate regions and genes tested, Df(2L)c17, Df(3L)Ly, Df(3L)AC1 and Df(3R)e-BS2 showed significant failure to complement wild-type alleles in both sexes, and an Alcohol dehydrogenase mutant failed to complement in females. Several genes that regulate life span (e.g., Superoxide dismutase, Catalase, and rosy) complemented the life span effects of wild-derived alleles, suggesting little natural variation affecting longevity at these loci, at least in this sample of alleles. Quantitative complementation tests are therefore useful for identifying QTL contributing to segregating genetic variation in life span in nature. PMID:15013662

Geiger-Thornsberry, Gretchen L; Mackay, Trudy F C

2004-03-01

57

Decoupled phenotypic variation between floral and vegetative traits: distinguishing between developmental and environmental correlations  

PubMed Central

Background and Aims In species with specialized pollination, floral traits are expected to be relatively invariant and decoupled from the phenotypic variation affecting vegetative traits. However, inferring the degree of decoupling between morphological characters from patterns of phenotypic correlations is difficult because phenotypic correlations result from the superimposition of several sources of covariance. In this study it is hypothesized that, in some cases, negative environmental correlations generated by non-congruent reaction norms across traits overshadow positive developmental correlations and generate a decoupling of the phenotypic variation between vegetative and floral traits. Methods To test this hypothesis, Campanula rotundifolia were grown from two distinct populations under two temperature treatments, and patterns of correlation were analysed between leaf size and flower size within and among treatments. Key Results Flower size was less sensitive to temperature variation than leaf size. Furthermore, flower size and leaf size showed temperature-induced reaction norms in opposite directions. Flower size decreased with an increasing temperature, while leaf size increased. Consequently, among treatments, correlations between leaf size and flower size were negative or absent, while, within treatments, these correlations were positive or absent in the cold and warm environments, respectively. Conclusions These results confirm that the decoupling of the phenotypic variation between vegetative and floral traits can be dependent on the environment. They also underline the importance of distinguishing sources of phenotypic covariance when testing hypotheses about phenotypic integration.

Pelabon, Christophe; Osler, Nora C.; Diekmann, Martin; Graae, Bente J.

2013-01-01

58

The nature of quantitative genetic variation for Drosophila longevity.  

PubMed

Longevity is a typical quantitative trait: the continuous variation in life span observed in natural populations is attributable to genetic variation at multiple quantitative trait loci (QTL), environmental sensitivity of QTL alleles, and truly continuous environmental variation. To begin to understand the genetic architecture of longevity at the level of individual QTL, we have mapped QTL for Drosophila life span that segregate between two inbred strains that were not selected for longevity. A mapping population of 98 recombinant inbred lines (RIL) was derived from these strains, and life span of virgin male and female flies measured under control culture conditions, chronic heat and cold stress, heat shock and starvation stress, and high and low density larval environments. The genotypes of the RIL were determined for polymorphic roo transposable element insertion sites, and life span QTL were mapped using composite interval mapping methods. A minimum of 19 life span QTL were detected by recombination mapping. The life span QTL exhibited strong genotype by sex, genotype by environment, and genotype by genotype (epistatic) interactions. These interactions complicate mapping efforts, but evolutionary theory predicts such properties of segregating QTL alleles. Quantitative deficiency mapping of four longevity QTL detected in the control environment by recombination mapping revealed a minimum of 11 QTL in these regions. Clearly, longevity is a complex quantitative trait. In the future, linkage disequilibrium mapping can be used to determine which candidate genes in a QTL region correspond to the genetic loci affecting variation in life span, and define the QTL alleles at the molecular level. PMID:11718804

Mackay, Trudy F C

2002-01-01

59

Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation  

PubMed Central

Purpose Previously, a 44 bp insertion in exon 2 of retinitis pigmentosa GTPase interacting protein 1 (RPGRIP1) was identified as the cause of cone-rod dystrophy 1 (cord1), a recessive form of progressive retinal atrophy (PRA) in the Miniature Longhaired Dachshund (MLHD), a dog model for Leber congenital amaurosis. The cord1 locus was mapped using MLHDs from an inbred colony with a homogeneous early onset disease phenotype. In this paper, the MLHD pet population was studied to investigate phenotypic variation and genotype-phenotype correlation. Further, the cord1 locus was fine-mapped using PRA cases from the MLHD pet population to narrow the critical region. Other dog breeds were also screened for the RGPRIP1 insertion. Methods This study examined phenotypic variation in an MLHD pet population that included 59 sporadic PRA cases and 18 members of an extended family with shared environment and having six PRA cases. Ophthalmologic evaluations included behavioral abnormalities, responses to menace and light, fundoscopy, and electroretinography (ERG). The RPGRIP1 insertion was screened for in all cases and 200 apparently normal control MLHDs and in 510 dogs from 66 other breed. To fine-map the cord1 locus in the MLHD, 74 PRA cases and 86 controls aged 4 years or more were genotyped for 24 polymorphic markers within the previously mapped cord1 critical region of 14.15 Mb. Results Among sporadic PRA cases from the MLHD pet population, the age of onset varied from 4 months to 15 years old; MLHDs from the extended family also showed variable onset and rate of progression. Screening for the insertion in RPGRIP1 identified substantial genotype-phenotype discordance: 16% of controls were homozygous for the insertion (RPGRIP1?/?), while 20% of PRA cases were not homozygous for it. Four other breeds were identified to carry the insertion including English Springer Spaniels and Beagles with insertion homozygotes. The former breed included both controls and PRA cases, yet in the latter breed, cone ERG was undetectable in two dogs with no clinically apparent visual dysfunction. Notably, the insertion in the Beagles was a longer variant of that seen in the other breeds. Fine-mapping of the cord1 locus narrowed the critical region on CFA15 from 14.15 Mb to 1.74 Mb which still contains the RPGRIP1 gene. Conclusions Extensive phenotypic variations of onset age and progression rate were observed in PRA cases of the MLHD pet population. The insertion in RPGRIP1 showed the strongest association with the disease, yet additional as well as alternative factors may account for the substantial genotype-phenotype discordance.

Kato, Kumiko; Aguirre-Hernandez, Jesus; Tokuriki, Tsuyoshi; Morimoto, Kyohei; Busse, Claudia; Barnett, Keith; Holmes, Nigel; Ogawa, Hiroyuki; Sasaki, Nobuo; Mellersh, Cathryn S.; Sargan, David R.

2009-01-01

60

The genotype-phenotype maps of systems biology and quantitative genetics: distinct and complementary.  

PubMed

The processes by which genetic variation in complex traits is generated and maintained in populations has for a long time been treated in abstract and statistical terms. As a consequence, quantitative genetics has provided limited insights into our understanding of the molecular bases of quantitative trait variation. With the developing technological and conceptual tools of systems biology, cellular and molecular processes are being described in greater detail. While we have a good description of how signaling and other molecular networks are organized in the cell, we still do not know how genetic variation affects these pathways, because systems and molecular biology usually ignore the type and extent of genetic variation found in natural populations. Here we discuss the quantitative genetics and systems biology approaches for the study of complex trait architecture and discuss why these two disciplines would synergize with each other to answer questions that neither of the two could answer alone. PMID:22821467

Landry, Christian R; Rifkin, Scott A

2012-01-01

61

MOLECULAR ABO PHENOTYPING IN CYNOMOLGUS MACAQUES USING REAL TIME QUANTITATIVE PCR (QPCR)  

PubMed Central

Macaques are commonly used in biomedical research as animal models of human disease. The ABO phenotype of donors and recipients plays an important role in the success of transplantation and stem cell research of both human and macaque tissue. Traditional serological methods for ABO phenotyping can be time consuming, provide ambiguous results and/or require tissue that is unavailable or unsuitable. We developed a novel method to detect the A, B, and AB phenotypes of macaques using real-time quantitative PCR. This method enables the simple and rapid screening of these phenotypes in macaques without the need for fresh blood or saliva. This study reports the distribution of the A, B, and AB phenotypes of captive cynomolgus macaques that, while regionally variable, closely resembles that of rhesus macaques. Blood group B, as in rhesus macaques, predominates in cynomolgus macaques and its frequency distribution leads to a probability of major incompatibility of 41%. No silencing mutations have been identified in exons 6 or 7 in macaques that could be responsible for the O phenotype, that, although rare, have been reported. The excess homozygosity of rhesus and cynomolgus macaque genotypes in the present study, that assumes the absence of the O allele, suggests the possibility of some mechanism preventing the expression of the A and B transferases.

Premasuthan, Amritha; Ng, Jillian; Kanthaswamy, Sreetharan; Trask, Jessica Satkoski; Houghton, Paul; Farkas, Tibor; Sestak, Karol; Smith, David Glenn

2012-01-01

62

Tissue Culture-Induced Heritable Genomic Variation in Rice, and Their Phenotypic Implications  

PubMed Central

Background Somaclonal variation generally occurs in plants regenerated from tissue culture. However, fundamental issues regarding molecular characteristics, mutation rates and mutation spectra of plant somatic variation as well as their phenotypic relevance have been addressed only recently. Moreover, these studies have reported highly discrepant results in different plant species and even in the same plant genotype. Methodology/principal findings We investigated heritable genomic variation induced by tissue culture in rice by whole genome re-sequencing of an extensively selfed somaclonal line (TC-reg-2008) and its wild type (WT) donor (cv. Hitomebore). We computed the overall mutation rate, single nucleotide polymorphisms (SNPs), small scale insertions/deletions (Indels) and mobilization of transposable elements (TEs). We assessed chromosomal distribution of the various types of genomic variations, tested correlations between SNPs and Indels, and examined concomitancy between TE activity and its cytosine methylation states. We also performed gene ontology (GO) analysis of genes containing nonsynonymous mutations and large-effect mutations, and assayed effects of the genomic variations on phenotypes under both normal growing condition and several abiotic stresses. We found that heritable somaclonal genomic variation occurred extensively in rice. The genomic variations distributed non-randomly across each of the 12 rice chromosomes, and affected a large number of functional genes. The phenotypic penetrance of the genomic variations was condition-dependent. Conclusions/significance Tissue culture is a potent means to generate heritable genetic variations in rice, which bear distinct difference at least in space (chromosomal distribution) from those occurred under natural settings. Our findings have provided new information regarding the mutation rate and spectrum as well as chromosomal distribution pattern of somaclonal variation in rice. Our data also suggest that rice possesses a strong capacity to canalize genetic variations under normal growing conditions to maintain phenotypic robustness, which however can be released by certain abiotic stresses to generate variable phenotypes.

Gao, Yang; Liu, Ying; Wu, Ying; Bai, Yan; Zhang, Zhibin; Lin, Xiuyun; Dong, Yuzhu; Ou, Xiufang; Xu, Chunming; Liu, Bao

2014-01-01

63

Genotype Matrix Mapping: Searching for Quantitative Trait Loci Interactions in Genetic Variation in Complex Traits  

PubMed Central

Abstract In order to reveal quantitative trait loci (QTL) interactions and the relationship between various interactions in complex traits, we have developed a new QTL mapping approach, named genotype matrix mapping (GMM), which searches for QTL interactions in genetic variation. The central approach in GMM is the following. (1) Each tested marker is given a virtual matrix, named a genotype matrix (GM), containing intersecting lines and rows equal to the total allele number for that marker in the population analyzed. (2) QTL interactions are then estimated and compared through virtual networks among the GMs. To evaluate the contribution of marker combinations to a quantitative phenotype, the GMM method divides the samples into two non-overlapping subclasses, S0 and S1; the former contains the samples that have a specific genotype pattern to be evaluated, and the latter contains samples that do not. Based on this division, the F-measure is calculated as an index of significance. With the GMM method, we extracted significant marker combinations consisting of one to three interacting markers. The results indicated there were multiple QTL interactions affecting the phenotype (flowering date). GMM will be a valuable approach to identify QTL interactions in genetic variation of a complex trait within a variety of organisms.

Isobe, Sachiko; Nakaya, Akihiro; Tabata, Satoshi

2007-01-01

64

Mechanisms for phenotypic variation in Lesch-Nyhan disease and its variants  

PubMed Central

Lesch–Nyhan disease is a neurogenetic disorder caused by mutation of the HPRT1 gene on the X chromosome. There is significant variation in the clinical phenotype, with more than 300 different known mutations. There are few studies that have addressed whether similar mutations result in similar phenotypes across different patients because hypoxanthine–guanine phosphoribosyltransferase (HGprt) deficiency is rare, and most mutations are unique or limited to individual families. However, recent studies have revealed multiple unrelated patients with similar mutations, providing an opportunity to examine genotype–phenotype correlations. We found significant variation among the clinical features of 10 patients from 8 unrelated families all carrying a mutation replacing guanine with adenine at base position 143 (c.143G>A) in the HPRT1 gene. This mutation results in replacement of arginine by histidine at amino acid position 48 (p.arg48his) in the HGprt enzyme. Biochemically, the enzyme exhibits reduced thermal integrity, a mechanism that may explain clinical variation. The literature reveals similar clinical variation among other patients with similar mutations, although the variation is relatively minor across the whole population of patients. Identifiable sources of clinical variation include known limitations of clinical ascertainment and mechanisms that affect residual enzyme activity and stability. These results are helpful for understanding genotype–phenotype correlations and discordance and likely are applicable to other neurogenetic disorders where similar variation occurs.

Sampat, Radhika; Fu, Rong; Larovere, Laura E.; Torres, Rosa J.; Ceballos-Picot, Irene; Fischbach, Michel; de Kremer, Raquel; Schretlen, David J.; Puig, Juan Garcia

2011-01-01

65

Plasmodium falciparum Heterochromatin Protein 1 Marks Genomic Loci Linked to Phenotypic Variation of Exported Virulence Factors  

Microsoft Academic Search

Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3

Christian Flueck; Richard Bartfai; Jennifer Volz; Igor Niederwieser; Adriana M. Salcedo-Amaya; Blaise T. F. Alako; Florian Ehlgen; Stuart A. Ralph; Alan F. Cowman; Zbynek Bozdech; Hendrik G. Stunnenberg; Till S. Voss

2009-01-01

66

Phenotypic variation in plants regenerated from protoplasts: the potato system  

SciTech Connect

Regeneration of whole plants from isolated protoplasts (plant cells devoid of cell walls) provides a novel capability that is potentially useful for crop improvement efforts. Such a regeneration capacity has been developed for the commercial potato cultivar 'russet Burbank,' currently the most popular cultivar in production. Due to fertility problems of this cultivar, the improvement of 'russet Burbank' by classical breeding procedures has been limited. Examination of a large population of protoplast-derived clones has revealed that variation for a number of traits can be observed. Variation observed under laboratory conditions and in field trials includes changes in plant morphology and tuber-setting characteristics, as well as alterations in response to environmental and pathogen stress. A brief description of the cloning process and the potential for application of cloning technology in crop plant improvement will be presented. (Refs. 41).

Bidney, D.L.; Shepard, J.F.

1981-12-01

67

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

PubMed Central

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 assessed by flow cytometry. This cohort of mice represents a wide range of genetic origins and includes most of the strains used in genetic, physiological, and immunological studies. We evaluated the relative percentages of peripheral blood leukocyte subtypes (lymphocytes, granulocytes, and monocytes) and lymphocyte subpopulations (CD4+ T, CD8+ T, B220+ B, and natural killer cells) of mature (6-mo-old) mice. Our comprehensive study demonstrated: 1) marked differences in the relative proportions of blood cell populations among the strains at this age, 2) considerable variation of each immune trait with more than twofold difference between strains with the highest and the lowest trait values, and 3) haplotype analysis revealed a strong correlation between eosinophil percentage and a single region on chromosome 14 containing two candidate genes. The strain differences described here provide important information for researchers applying immunophenotyping of peripheral blood in immunological and genetic studies. The data from this study are available as part of the Mouse Phenome Database at http://www.jax.org/phenome.

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

2008-01-01

68

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

PubMed Central

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.

Gianola, Daniel; Sorensen, Daniel

2004-01-01

69

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

Microsoft Academic Search

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

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

2008-01-01

70

Phenotypic variation and fluctuating asymmetry in sexually dimorphic feather ornaments in relation to sex and mating system  

Microsoft Academic Search

Secondary sexual characters have been hypothesized to demonstrate increased phenotypic variation between and within individuals as compared to ordinary morphological traits. We tested whether this was the case by studying phenotypic variation, expressed as the coefficient of variation (CV), and developmental instability, measured as fluctuating asymmetry (FA), in ornamental and non-ornamental traits of 70 bird species with feather ornamentation while

JOSÉ JAVIER CUERVO; ANDERS PAPE MØLLER

1999-01-01

71

Effects of Phenotyping Environment on Identification of Quantitative Trait Loci for Rice Root Morphology under Anaerobic Conditions.  

PubMed

In the rainfed lowlands, rice (Oryza sativa L.) develops roots under anaerobic soil conditions with ponded water, prior to exposure to aerobic soil conditions and water stress. Constitutive root system development in anaerobic soil conditions has been reported to have a positive effect on subsequent expression of adaptive root traits and water extraction during water stress. We examined effects of phenotyping environment on identification of quantitative trait loci (QTLs) for constitutive root morphology traits using 220 doubled-haploid lines (DHLs) from the cross of 'CT9993-5-10-1-M' (CT9993; japonica, upland adapted) x 'IR62266-42-6-2' (IR62266; indica, lowland adapted) in four greenhouse experiments. Broad sense heritability (h(2)) was 75, 60, and 64% on average for shoot biomass, deep root morphology, and root thickness traits, respectively. Quantitative trait loci analysis identified 18 genomic regions associated with deep root morphology traits, but only three were identified consistently across experiments. Three out of a total of eight QTLs for root thickness traits were found in more than one experiment. The maximum genetic effects caused by a single QTL were increments of 0.05 g of deep root mass below a 30-cm soil depth, 0.9% of deep root ratio, 1.6 cm of rooting depth, and 0.09 cm of root thickness, with phenotypic variation explained by a single QTL ranging from 6.8 to 51.8%. The results demonstrate the importance of phenotyping environment and suggest prospects for selection of QTLs for deep root morphology, root thickness, and vigorous seedling growth under anaerobic conditions to improve the constitutive root system of rainfed lowland rice. There was some consistency in QTL regions identified, despite the presence of QTL x environment interactions. PMID:11756283

Kamoshita, A.; Zhang, Jingxian; Siopongco, J.; Sarkarung, S.; Nguyen, H. T.; Wade, L. J.

2002-01-01

72

The change in quantitative genetic variation with inbreeding.  

PubMed

Inbreeding is known to reduce heterozygosity of neutral genetic markers, but its impact on quantitative genetic variation is debated. Theory predicts a linear decline in additive genetic variance (V(A)) with increasing inbreeding coefficient (F) when loci underlying the trait act additively, but a nonlinear hump-shaped relationship when dominance and epistasis are important. Predictions for heritability (h2) are similar, although the exact shape depends on the value of h2 in the absence of inbreeding. We located 22 published studies in which the level of genetic variation in experimentally inbred populations (measured by V(A) or h2) was compared with that in outbred control populations. For life-history traits, the data strongly supported a nonlinear change in genetic variation with increasing F. V(A) and h2 were, respectively, 244% and 50% higher at F = 0.4 than in outbred populations, and dominance plus epistatic variance together exceeded additive variance by a factor of four. For nonfitness traits the decline was linear and estimates of nonadditive variance were small. These results confirm that population bottlenecks frequently increase V(A) in some traits, and imply that life-history traits are underlain by substantial dominance or epistasis. However, the importance of drift-induced genetic variation in conservation or evolutionary biology is questionable, in part because inbreeding depression usually accompanies inbreeding. PMID:17263106

Van Buskirk, Josh; Willi, Yvonne

2006-12-01

73

Temperature-dependent phenotypic variation of Campylobacter jejuni lipooligosaccharides  

PubMed Central

Background Campylobacter jejuni is a major bacterial cause of food-borne enteritis, and its lipooligosaccharide (LOS) plays an initiating role in the development of the autoimmune neuropathy, Guillain-Barré syndrome, by induction of anti-neural cross-reactive antibodies through ganglioside molecular mimicry. Results Herein we describe the existence and heterogeneity of multiple LOS forms in C. jejuni strains of human and chicken origin grown at 37°C and 42°C, respectively, as determined on sodium dodecyl sulphate-polyacrylamide electrophoresis gels with carbohydrate-specific silver staining and blotting with anti-ganglioside ligands, and confirmed by nuclear magnetic resonance (NMR) spectroscopy. The C. jejuni NCTC 11168 original isolate (11168-O) was compared to its genome-sequenced variant (11168-GS), and both were found to have a lower-Mr LOS form, which was different in size and structure to the previously characterized higher-Mr form bearing GM1 mimicry. The lower-Mr form production was found to be dependent on the growth temperature as the production of this form increased from ~5%, observed at 37°C to ~35% at 42°C. The structure of the lower-Mr form contained a ?-D-Gal-(1?3)-?-D-GalNAc disaccharide moiety which is consistent with the termini of the GM1, asialo-GM1, GD1, GT1 and GQ1 gangliosides, however, it did not display GM1 mimicry as assessed in blotting studies but was shown in NMR to resemble asialo-GM1. The production of multiple LOS forms and lack of GM1 mimicry was not a result of phase variation in the genes tested of NCTC 11168 and was also observed in most of the human and chicken isolates of C. jejuni tested. Conclusion The presence of differing amounts of LOS forms at 37 and 42°C, and the variety of forms observed in different strains, indicate that LOS form variation may play a role in an adaptive mechanism or a stress response of the bacterium during the colonization of different hosts.

2010-01-01

74

The constancy of the G matrix through species divergence and the effects of quantitative genetic constraints on phenotypic evolution: a case study in crickets.  

PubMed

Long-term phenotypic evolution can be modeled using the response-to-selection equation of quantitative genetics, which incorporates information about genetic constraints (the G matrix). However, little is known about the evolution of G and about its long-term importance in constraining phenotypic evolution. We first investigated the degree of conservation of the G matrix across three species of crickets and qualitatively compared the pattern of variation of G to the phylogeny of the group. Second, we investigated the effect of G on phenotypic evolution by comparing the direction of greatest quantitative genetic variation within species (g(max)) to the direction of phenotypic divergence between species (Delta(z)). Each species, Gryllus veletis, G. firmus, and G. pennsylvanicus, was reared in the laboratory using a full-sib breeding design to extract quantitative genetic information. Five morphological traits related to size were measured. G matrices were compared using three statistical approaches: the T method, the Flury hierarchy, and the MANOVA method. Results revealed that the differences between matrices were small and mostly caused by differences in the magnitude of the genetic variation, not by differences in principal component structure. This suggested that the G matrix structure of this group of species was preserved, despite significant phenotypic divergence across species. The small observed differences in G matrices across species were qualitatively consistent with genetic distances, whereas ecological information did not provide a good prediction of G matrix variation. The comparison of g(max) and Delta(z) revealed that the angle between these two vectors was small in two of three species comparisons, whereas the larger angle corresponding to the third species comparison was caused in large part by one of the five traits. This suggests that multivariate phenotypic divergence occurred mostly in a direction predicted by the direction of greatest genetic variation, although it was not possible to demonstrate the causal relationship from G to Delta(z). Overall, this study provided some support for the validity of the predictive power of quantitative genetics over evolutionary time scales. PMID:12836827

Bégin, Mattieu; Roff, Derek A

2003-05-01

75

Phenotypic plasticity facilitates mutational variance, genetic variance, and evolvability along the major axis of environmental variation.  

PubMed

Phenotypically plastic genotypes express different phenotypes in different environments, often in adaptive ways. The evolution of phenotypic plasticity creates developmental systems that are more flexible along the trait dimensions that are more plastic, and as a result, we hypothesize that such traits will express greater mutational variance, genetic variance, and evolvability. We develop an explicit gene network model with three components: some genes can receive environmental cues about the adult selective environment, some genes that interact repeatedly to determine each others' final state, and other factors that translate these final expression states into the phenotype. We show that the evolution of phenotypic plasticity is an important determinant of mutational patterns, genetic variance, and evolutionary potential of a population. Phenotypic plasticity tends to lead to populations with greater mutational variance, greater standing genetic variance, and, when the optimal phenotypes of two traits vary in concert, greater mutational and genetic correlations. However, plastic populations do not tend to respond much more rapidly to selection than do populations evolved in a static environment. We find that the quantitative genetic descriptions of traits created by explicit developmental network models are evolutionarily labile, with genetic correlations that change rapidly with shifts in the selection regime. PMID:22946810

Draghi, Jeremy A; Whitlock, Michael C

2012-09-01

76

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

PubMed

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

Lande, R

2014-05-01

77

Localised intraspecific variation in the swimming phenotype of a coral reef fish across different wave exposures.  

PubMed

Wave-driven water flow is a major force structuring marine communities. Species distributions are partly determined by the ability to cope with variation in water flow, such as differences in the assemblage of fish species found in a given water flow environment being linked to swimming ability (based on fin shape and mode of locomotion). It remains unclear, however, whether similar assembly rules apply within a species. Here we show phenotypic variation among sites in traits functionally linked to swimming ability in the damselfish Acanthochromis polyacanthus. These sites differ in wave energy and the observed patterns of phenotypic differences within A. polyacanthus closely mirrored those seen at the interspecific level. Fish from high-exposure sites had more tapered fins and higher maximum metabolic rates than conspecifics from sheltered sites. This translates to a 36% larger aerobic scope and 33% faster critical swimming speed for fish from exposed sites. Our results suggest that functional relationships among swimming phenotypes and water flow not only structure species assemblages, but can also shape patterns of phenotypic divergence within species. Close links between locomotor phenotype and local water flow conditions appear to be important for species distributions as well as phenotypic divergence across environmental gradients. PMID:24132502

Binning, Sandra A; Roche, Dominique G; Fulton, Christopher J

2014-03-01

78

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

Microsoft Academic Search

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

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

79

PHENOTYPIC VARIATION OF LARKS ALONG AN ARIDITY GRADIENT: ARE DESERT BIRDS MORE FLEXIBLE?  

Microsoft Academic Search

We investigated interindividual variation and intra-individual phenotypic flexibility in basal metabolic rate (BMR), total evaporative water loss (TEWL), body tem- perature (Tb), the minimum dry heat transfer coefficient (h), and organ and muscle size of five species of larks geographically distributed along an aridity gradient. We exposed all species to constant environments of 158 Co r 358C, and examined to

B. Irene Tieleman; Joseph B. Williams; Michael E. Buschur; Chris R. Brown

2003-01-01

80

Reverse engineering the genotype-phenotype map with natural genetic variation  

Microsoft Academic Search

The genetic variation that occurs naturally in a population is a powerful resource for studying how genotype affects phenotype. Each allele is a perturbation of the biological system, and genetic crosses, through the processes of recombination and segregation, randomize the distribution of these alleles among the progeny of a cross. The randomized genetic perturbations affect traits directly and indirectly, and

Matthew V. Rockman

2008-01-01

81

The Role of Phenotypic Plasticity in Color Variation of Tularosa Basin Lizards  

Microsoft Academic Search

An experimental approach was taken to evaluate the role of phenotypic plasticity in reptile coloration for three lizard species which exhibit dramatic variation in dorsal body darkness associated with different substrate environments. In southern New Mexico, blanched color morphs of Aspidoscelis inornata, Holbrookia maculata, and Sceloporus undulatus inhabit the gypsum dunes of White Sands, and a melanic color morph of

Erica Bree Rosenblum; S. J. Beaupre

2005-01-01

82

Variation in pollinator abundance and selection on fragrance phenotypes in an epiphytic orchid.  

PubMed

Extraordinary floral variation is common among some orchids that employ deception to attract pollinators. This variation may be maintained by frequency-dependent selection where rare phenotypes are preferred. Over a 2-yr period, 1993-1994, we monitored the reproductive success of Tolumnia variegata, an obligately outcrossing epiphytic orchid, at three localities in Puerto Rico that differed in pollinator service. Plants varied in floral morphology and fragrance characteristics. Artificial arrays of varying frequencies of scentless and fragrant phenotypes were established to test for frequency-dependent selection. Where pollinators were rare (Cambalache, range of census average = 0-0.2 bees/h), 0.9-1.2% of the flowers were effectively visited (pollinarium removals and pollinations). At Tortuguero where 0.4-1.1 bees/h were observed, 4-9.2% of the flowers were visited. At Pi;atnones where bees were the most abundant (1.4-5.2 bees/h), 20.9-25.0% of the flowers were visited. A significant portion of the variance in all measures of reproductive success (male, female, and combined) was explained by differences among populations, which we attribute mostly to variation in pollinator abundance. Neither the fragrance phenotype nor its frequency had a significant effect on success as revealed by a split-plot ANOVA. There was a significant interaction between population and phenotypic frequencies in all our measures of reproductive success, but only for the 1994 flowering season. Thus, variation in floral fragrance phenotypes is not likely maintained by frequency-dependent selection. High levels of variation remain unexplained. PMID:21708546

Ackerman, J; Melendez-Ackerman, E; Salguero-Faria, J

1997-10-01

83

A quantitative study of gene regulatory pathways in Bacillus subtilis for virulence and competence phenotype by quorum sensing.  

PubMed

Quorum sensing (QS) is a process which allows a population of bacteria to coordinately regulate gene expression of their entire community. Bacillus subtilis is a soil organism which uses QS to alternate between competence for DNA uptake and sporulation. We propose a model to describe the components involved in QS and to analyze reaction species involved in the regulation of QS machinery. We targeted only those QS phenotypes for which the genetic organization and molecular characterization of the components are fully elucidated. We have analyzed simulations for concentration of different species involved in competence as well as sporulation pathways at diverse time period using quantitative methods. It was observed that there is possibility of achieving different measurement from reactions taken place between species by applying irreversible Michaelis-Menten kinetic law. We obtain variation in measurement on changing parameters such as concentrations ranging from 0.3 to 50 ?M in stepwise manner by setting end time in the range of 0.1-100 ms. Additionally we observe covariance between different reaction species involved in QS by fluctuating their quantities in real-time simulations. Our model mimics correctly the phenotype for competence and virulence. We concluded that time factor play major role to determine rate kinetics of diverse reaction species as compared to their concentrations and support the hypothesis of getting genetic stability while colonies are in synchronization. PMID:24432140

Kumar, Ashwani; Singh, Tiratha Raj

2013-06-01

84

Phenotypic variation of Staphylococcus epidermidis isolated from a patient with native valve endocarditis.  

PubMed Central

Two colonial variants of Staphylococcus epidermidis were isolated from the valvular tissue of a patient with native valve endocarditis. In addition to differing in colonial morphology, the two variants differed in hemolysis on blood-containing media, in adherence capacity, and in the expression of certain enzymes. Under suitable conditions, both variants were themselves capable of phenotypic variation, although they differed in the rate at which variants were generated. The variants yielded identical profiles on restriction endonuclease analysis of plasmid DNA and pulsed-field gel electrophoresis of whole-cell DNA. This report suggests a possible role for phenotypic variation in coagulase-negative staphylococcal virulence. Congo red agar would be an excellent medium for studying the contribution of variation to the virulence of these organisms. Images

Deighton, M; Pearson, S; Capstick, J; Spelman, D; Borland, R

1992-01-01

85

Environmental Heterogeneity and Phenotypic Divergence: Can Heritable Epigenetic Variation Aid Speciation?  

PubMed Central

The dualism of genetic predisposition and environmental influences, their interactions, and respective roles in shaping the phenotype have been a hot topic in biological sciences for more than two centuries. Heritable epigenetic variation mediates between relatively slowly accumulating mutations in the DNA sequence and ephemeral adaptive responses to stress, thereby providing mechanisms for achieving stable, but potentially rapidly evolving phenotypic diversity as a response to environmental stimuli. This suggests that heritable epigenetic signals can play an important role in evolutionary processes, but so far this hypothesis has not been rigorously tested. A promising new area of research focuses on the interaction between the different molecular levels that produce phenotypic variation in wild, closely-related taxa that lack genome-wide genetic differentiation. By pinpointing specific adaptive traits and investigating the mechanisms responsible for phenotypic differentiation, such study systems could allow profound insights into the role of epigenetics in the evolution and stabilization of phenotypic discontinuities, and could add to our understanding of adaptive strategies to diverse environmental conditions and their dynamics.

Flatscher, Ruth; Frajman, Bozo; Schonswetter, Peter; Paun, Ovidiu

2012-01-01

86

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

PubMed

Phenotype is often correlated with resource use, which suggests that as phenotypic variation in a population increases, intraspecific competition will decrease. However, few studies have experimentally tested the prediction that increased intraspecific phenotypic variation leads to reduced competitive effects (e.g., on growth rate, survival or reproductive rate). We investigated this prediction with two experiments on wood frogs (Rana sylvatica). In the first experiment, we found that a frog's size was positively correlated with the size of its preferred prey, indicating that the feeding niche of the frogs changed with size. In the second experiment, we used an experimental design in which we held the initial mass of "focal" frogs constant, but varied the initial mass of their competitors. We found a significant quadratic effect of the average mass of competitors: focal frog growth was lowest when raised with similar-sized competitors, and highest when raised with competitors that were larger or smaller. Our results demonstrate that growth rates increase (i.e., competitive intensity decreases) when individuals are less similar to other members of the population and exhibit less overlap in resource use. Thus, changes in the amount of phenotypic variation in a population may ultimately affect population-level processes, such as population growth rate and extinction risk. PMID:21221649

Benard, Michael F; Middlemis Maher, Jessica

2011-07-01

87

Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach  

PubMed Central

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.

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

2014-01-01

88

Genetic variation in flowering time induces phenological assortative mating: quantitative genetic methods applied to Brassica rapa  

Microsoft Academic Search

It has been argued from first principles that plants mate assortatively by flowering time. However, there have been very few studies of phenological assortative mating, perhaps because current methods to infer paternal phenotype are difficult to apply to natural populations. Two methods are presented to estimate the phenotypic correlation between mates—the quantitative genetic metric for assortative mating—for phenological traits. The

ARTHUR E. WEIS; TANYA M. KOSSLER

2004-01-01

89

Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers.  

PubMed

The Genetics Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer's disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development. PMID:24092460

Shen, Li; Thompson, Paul M; Potkin, Steven G; Bertram, Lars; Farrer, Lindsay A; Foroud, Tatiana M; Green, Robert C; Hu, Xiaolan; Huentelman, Matthew J; Kim, Sungeun; Kauwe, John S K; Li, Qingqin; Liu, Enchi; Macciardi, Fabio; Moore, Jason H; Munsie, Leanne; Nho, Kwangsik; Ramanan, Vijay K; Risacher, Shannon L; Stone, David J; Swaminathan, Shanker; Toga, Arthur W; Weiner, Michael W; Saykin, Andrew J

2014-06-01

90

Genetic variation for phenotypically invariant traits detected in teosinte: implications for the evolution of novel forms.  

PubMed Central

How new discrete states of morphological traits evolve is poorly understood. One possibility is that single-gene changes underlie the evolution of new discrete character states and that evolution is dependent on the occurrence of new single-gene mutations. Another possibility is that multiple-gene changes are required to elevate an individual or population above a threshold required to produce the new character state. A prediction of the latter model is that genetic variation for the traits should exist in natural populations in the absence of phenotypic variation. To test this idea, we studied traits that are phenotypically invariant within teosinte and for which teosinte is discretely different from its near relative, maize. By employing a QTL mapping strategy to analyze the progeny of a testcross between an F(1) of two teosintes and a maize inbred line, we identified cryptic genetic variation in teosinte for traits that are invariant in teosinte. We argue that such cryptic genetic variation can contribute to the evolution of novelty when reconfigured to exceed the threshold necessary for phenotypic expression or by acting to modify or stabilize the effects of major mutations.

Lauter, Nick; Doebley, John

2002-01-01

91

Selection in a fluctuating environment leads to decreased genetic variation and facilitates the evolution of phenotypic plasticity.  

PubMed

Changes in the environment are expected to induce changes in the quantitative genetic variation, which influences the ability of a population to adapt to environmental change. Furthermore, environmental changes are not constant in time, but fluctuate. Here, we investigate the effect of rapid, continuous and/or fluctuating temperature changes in the seed beetle Callosobruchus maculatus, using an evolution experiment followed by a split-brood experiment. In line with expectations, individuals responded in a plastic way and had an overall higher potential to respond to selection after a rapid change in the environment. After selection in an environment with increasing temperature, plasticity remained unchanged (or decreased) and environmental variation decreased, especially when fluctuations were added; these results were unexpected. As expected, the genetic variation decreased after fluctuating selection. Our results suggest that fluctuations in the environment have major impact on the response of a population to environmental change; in a highly variable environment with low predictability, a plastic response might not be beneficial and the response is genetically and environmentally canalized resulting in a low potential to respond to selection and low environmental sensitivity. Interestingly, we found greater variation for phenotypic plasticity after selection, suggesting that the potential for plasticity to evolve is facilitated after exposure to environmental fluctuations. Our study highlights that environmental fluctuations should be considered when investigating the response of a population to environmental change. PMID:22519748

Hallsson, L R; Björklund, M

2012-07-01

92

Genotypic and phenotypic variation in transmission traits of a complex life cycle parasite  

PubMed Central

Characterizing genetic variation in parasite transmission traits and its contribution to parasite vigor is essential for understanding the evolution of parasite life-history traits. We measured genetic variation in output, activity, survival, and infection success of clonal transmission stages (cercaria larvae) of a complex life cycle parasite (Diplostomum pseudospathaceum). We further tested if variation in host nutritional stage had an effect on these traits by keeping hosts on limited or ad libitum diet. The traits we measured were highly variable among parasite genotypes indicating significant genetic variation in these life-history traits. Traits were also phenotypically variable, for example, there was significant variation in the measured traits over time within each genotype. However, host nutritional stage had no effect on the parasite traits suggesting that a short-term reduction in host resources was not limiting the cercarial output or performance. Overall, these results suggest significant interclonal and phenotypic variation in parasite transmission traits that are not affected by host nutritional status.

Louhi, Katja-Riikka; Karvonen, Anssi; Rellstab, Christian; Jokela, Jukka

2013-01-01

93

Genotypic and phenotypic variation in transmission traits of a complex life cycle parasite.  

PubMed

Characterizing genetic variation in parasite transmission traits and its contribution to parasite vigor is essential for understanding the evolution of parasite life-history traits. We measured genetic variation in output, activity, survival, and infection success of clonal transmission stages (cercaria larvae) of a complex life cycle parasite (Diplostomum pseudospathaceum). We further tested if variation in host nutritional stage had an effect on these traits by keeping hosts on limited or ad libitum diet. The traits we measured were highly variable among parasite genotypes indicating significant genetic variation in these life-history traits. Traits were also phenotypically variable, for example, there was significant variation in the measured traits over time within each genotype. However, host nutritional stage had no effect on the parasite traits suggesting that a short-term reduction in host resources was not limiting the cercarial output or performance. Overall, these results suggest significant interclonal and phenotypic variation in parasite transmission traits that are not affected by host nutritional status. PMID:23919156

Louhi, Katja-Riikka; Karvonen, Anssi; Rellstab, Christian; Jokela, Jukka

2013-07-01

94

Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles.  

PubMed

The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics. PMID:18304490

Bruder, Carl E G; Piotrowski, Arkadiusz; Gijsbers, Antoinet A C J; Andersson, Robin; Erickson, Stephen; Diaz de Ståhl, Teresita; Menzel, Uwe; Sandgren, Johanna; von Tell, Desiree; Poplawski, Andrzej; Crowley, Michael; Crasto, Chiquito; Partridge, E Christopher; Tiwari, Hemant; Allison, David B; Komorowski, Jan; van Ommen, Gert-Jan B; Boomsma, Dorret I; Pedersen, Nancy L; den Dunnen, Johan T; Wirdefeldt, Karin; Dumanski, Jan P

2008-03-01

95

A pleiotropic nonadditive model of variation in quantitative traits  

SciTech Connect

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.

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

1994-11-01

96

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

PubMed Central

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.

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

2009-01-01

97

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

PubMed

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 F(st)-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

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

2009-11-01

98

Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons.  

PubMed

The canalization concept describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways, indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability. Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis. PMID:20062045

Specchia, Valeria; Piacentini, Lucia; Tritto, Patrizia; Fanti, Laura; D'Alessandro, Rosalba; Palumbo, Gioacchino; Pimpinelli, Sergio; Bozzetti, Maria P

2010-02-01

99

Phenotypic variation and magnetic resonance imaging (MRI) in Salla disease, a free sialic acid storage disorder.  

PubMed

Salla disease (SD) is a recessively inherited lysosomal storage disorder particularly common in the Finnish population. Patients with SD are normal at birth, but develop psychomotor delay and ataxia during the first year of life. Phenotypic variation of SD is wide, ranging from severely disabled children to mentally retarded adults capable of living under sheltered conditions. In the present study four unusually severely affected patients were investigated by detailed clinical examination, magnetic resonance imaging (MRI) and analysis of the excretion of free sialic acid in urine. MRI study, reported here for the first time, revealed a similarly defective myelination pattern in seven patients. The myelination process seemed to cessate at the level of an infant of a few months of age. Genetic linkage study of the families of the severely affected patients suggested linkage to the recently discovered SD locus on the long arm of chromosome 6. Locus heterogeneity therefore is an unlikely explanation of the phenotypic variation in SD. PMID:7885532

Haataja, L; Parkkola, R; Sonninen, P; Vanhanen, S L; Schleutker, J; Aärimaa, T; Turpeinen, U; Renlund, M; Aula, P

1994-10-01

100

Fractal and Transgenerational Genetic Effects on Phenotypic Variation and Disease Risk  

NASA Astrophysics Data System (ADS)

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.

Nadeau, Joe

101

Earlier Migration Timing, Decreasing Phenotypic Variation, and Biocomplexity in Multiple Salmonid Species  

PubMed Central

Climate-induced phenological shifts can influence population, evolutionary, and ecological dynamics, but our understanding of these phenomena is hampered by a lack of long-term demographic data. We use a multi-decade census of 5 salmonid species representing 14 life histories in a warming Alaskan stream to address the following key questions about climate change and phenology: How consistent are temporal patterns and drivers of phenology for similar species and alternative life histories? Are shifts in phenology associated with changes in phenotypic variation? How do phenological changes influence the availability of resource subsidies? For most salmonid species, life stages, and life histories, freshwater temperature influences migration timing – migration events are occurring earlier in time (mean?=?1.7 days earlier per decade over the 3–5 decades), and the number of days over which migration events occur is decreasing (mean?=?1.5 days per decade). Temporal trends in migration timing were not correlated with changes in intra-annual phenotypic variation, suggesting that these components of the phenotypic distribution have responded to environmental change independently. Despite commonalities across species and life histories, there was important biocomplexity in the form of disparate shifts in migration timing and variation in the environmental factors influencing migration timing for alternative life history strategies in the same population. Overall, adult populations have been stable during these phenotypic and environmental changes (? ?1.0), but the temporal availability of salmon as a resource in freshwater has decreased by nearly 30 days since 1971 due to changes in the median date of migration timing and decreases in intra-annual variation in migration timing. These novel observations advance our understanding of phenological change in response to climate warming, and indicate that climate change has influenced the ecology of salmon populations, which will have important consequences for the numerous species that depend on this resource.

Kovach, Ryan P.; Joyce, John E.; Echave, Jesse D.; Lindberg, Mark S.; Tallmon, David A.

2013-01-01

102

Sexual variation in assimilation efficiency: its link to phenotype and potential role in sexual dimorphism.  

PubMed

Sex-specific variation in morphology (sexual dimorphism) is a prevalent phenomenon among animals, and both dietary intake and resource allocation strategies influence sexually dimorphic traits (e.g., body size or composition). However, we investigated whether assimilation efficiency (AE), an intermediate step between dietary intake and allocation, can also vary between the sexes. Specifically, we tested whether sex-based differences in AE can explain variation in phenotypic traits. We measured morphometric characteristics (i.e., body length, mass, condition, and musculature) and AE of total energy, crude protein, and crude fat in post-reproductive adult Children's pythons (which exhibit a limited female-biased sexual size dimorphism) fed both low and high dietary intakes. Meal size was negatively related to AE of energy. Notably, male snakes absorbed crude protein more efficiently and increased epaxial (dorsal) musculature faster than females, which demonstrates a link between AE and phenotype. However, females grew in body length faster but did not absorb any nutrient more efficiently than males. Although our results do not provide a direct link between AE and sexual size dimorphism, they demonstrate that sexual variation in nutrient absorption exists and can contribute to other types of sex-based differences in phenotype (i.e., sexual dimorphism in growth of musculature). Hence, testing the broader applicability of AE's role in sexually dimorphic traits among other species is warranted. PMID:21104089

Stahlschmidt, Zachary R; Davis, Jon R; Denardo, Dale F

2011-04-01

103

Digital holographic microscopy: a quantitative label-free microscopy technique for phenotypic screening.  

PubMed

Digital Holographic Microscopy (DHM) is a label-free imaging technique allowing visualization of transparent cells with classical imaging cell culture plates. The quantitative DHM phase contrast image provided is related both to the intracellular refractive index and to cell thickness. DHM is able to distinguish cellular morphological changes on two representative cell lines (HeLa and H9c2) when treated with doxorubicin and chloroquine, two cytotoxic compounds yielding distinct phenotypes. We analyzed parameters linked to cell morphology and to the intracellular content in endpoint measurements and further investigated them with timelapse recording. The results obtained by DHM were compared with other optical label-free microscopy techniques, namely Phase Contrast, Differential Interference Contrast and Transport of Intensity Equation (reconstructed from three bright-field images). For comparative purposes, images were acquired in a common 96-well plate format on the different motorized microscopes. In contrast to the other microscopies assayed, images generated with DHM can be easily quantified using a simple automatized on-the-fly analysis method for discriminating the different phenotypes generated in each cell line. The DHM technology is suitable for the development of robust and unbiased image-based assays. PMID:24152227

Rappaz, Benjamin; Breton, Billy; Shaffer, Etienne; Turcatti, Gerardo

2014-01-01

104

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

PubMed Central

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.

Sharon, Eran

2014-01-01

105

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

PubMed

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

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

2014-05-01

106

Production of different phenotypes from the same genotype in the same environment by developmental variation.  

PubMed

The phenotype of an organism is determined by the genes, the environment and stochastic developmental events. Although recognized as a basic biological principle influencing life history, susceptibility to diseases, and probably evolution, developmental variation (DV) has been only poorly investigated due to the lack of a suitable model organism. This obstacle could be overcome by using the recently detected, robust and highly fecund parthenogenetic marbled crayfish as an experimental animal. Batch-mates of this clonal crayfish, which were shown to be isogenic by analysis of nuclear microsatellite loci, exhibited surprisingly broad ranges of variation in coloration, growth, life-span, reproduction, behaviour and number of sense organs, even when reared under identical conditions. Maximal variation was observed for the marmorated coloration, the pattern of which was unique in each of the several hundred individuals examined. Variation among identically raised batch-mates was also found with respect to fluctuating asymmetry, a traditional indicator of the epigenetic part of the phenotype, and global DNA methylation, an overall molecular marker of an animal's epigenetic state. Developmental variation was produced in all life stages, probably by reaction-diffusion-like patterning mechanisms in early development and non-linear, self-reinforcing circuitries involving behaviour and metabolism in later stages. Our data indicate that, despite being raised in the same environment, individual genotypes can map to numerous phenotypes via DV, thus generating variability among clone-mates and individuality in a parthenogenetic species. Our results further show that DV, an apparently ubiquitous phenomenon in animals and plants, can introduce components of randomness into life histories, modifying individual fitness and population dynamics. Possible perspectives of DV for evolutionary biology are discussed. PMID:18245627

Vogt, Günter; Huber, Martin; Thiemann, Markus; van den Boogaart, Gerald; Schmitz, Oliver J; Schubart, Christoph D

2008-02-01

107

The Developmental Basis of Variational Modularity: Insights from Quantitative Genetics, Morphometrics, and Developmental Biology  

Microsoft Academic Search

Groups of correlated characters (variational modules) often are considered to be the result of dissociated local developmental\\u000a factors, i.e., of a modular genotype–phenotype map. But certain sets of pleiotropic factors can equally well induce modular\\u000a phenotypic variation—no local developmental factors are necessary for a modular covariance structure. It is thus not possible\\u000a to infer genetic or developmental modularity from standing

Philipp Mitteroecker

2009-01-01

108

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

PubMed

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

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

2011-08-01

109

Quantitative trait loci mapping of phenotypic plasticity and genotype-environment interactions in plant and insect performance  

PubMed Central

Community genetic studies generally ignore the plasticity of the functional traits through which the effect is passed from individuals to the associated community. However, the ability of organisms to be phenotypically plastic allows them to rapidly adapt to changing environments and plasticity is commonly observed across all taxa. Owing to the fitness benefits of phenotypic plasticity, evolutionary biologists are interested in its genetic basis, which could explain how phenotypic plasticity is involved in the evolution of species interactions. Two current ideas exist: (i) phenotypic plasticity is caused by environmentally sensitive loci associated with a phenotype; (ii) phenotypic plasticity is caused by regulatory genes that simply influence the plasticity of a phenotype. Here, we designed a quantitative trait loci (QTL) mapping experiment to locate QTL on the barley genome associated with barley performance when the environment varies in the presence of aphids, and the composition of the rhizosphere. We simultaneously mapped aphid performance across variable rhizosphere environments. We mapped main effects, QTL × environment interaction (QTL×E), and phenotypic plasticity (measured as the difference in mean trait values) for barley and aphid performance onto the barley genome using an interval mapping procedure. We found that QTL associated with phenotypic plasticity were co-located with main effect QTL and QTL×E. We also located phenotypic plasticity QTL that were located separately from main effect QTL. These results support both of the current ideas of how phenotypic plasticity is genetically based and provide an initial insight into the functional genetic basis of how phenotypically plastic traits may still be important sources of community genetic effects.

Tetard-Jones, C.; Kertesz, M. A.; Preziosi, R. F.

2011-01-01

110

Quantitative trait loci mapping of phenotypic plasticity and genotype-environment interactions in plant and insect performance.  

PubMed

Community genetic studies generally ignore the plasticity of the functional traits through which the effect is passed from individuals to the associated community. However, the ability of organisms to be phenotypically plastic allows them to rapidly adapt to changing environments and plasticity is commonly observed across all taxa. Owing to the fitness benefits of phenotypic plasticity, evolutionary biologists are interested in its genetic basis, which could explain how phenotypic plasticity is involved in the evolution of species interactions. Two current ideas exist: (i) phenotypic plasticity is caused by environmentally sensitive loci associated with a phenotype; (ii) phenotypic plasticity is caused by regulatory genes that simply influence the plasticity of a phenotype. Here, we designed a quantitative trait loci (QTL) mapping experiment to locate QTL on the barley genome associated with barley performance when the environment varies in the presence of aphids, and the composition of the rhizosphere. We simultaneously mapped aphid performance across variable rhizosphere environments. We mapped main effects, QTL × environment interaction (QTL×E), and phenotypic plasticity (measured as the difference in mean trait values) for barley and aphid performance onto the barley genome using an interval mapping procedure. We found that QTL associated with phenotypic plasticity were co-located with main effect QTL and QTL×E. We also located phenotypic plasticity QTL that were located separately from main effect QTL. These results support both of the current ideas of how phenotypic plasticity is genetically based and provide an initial insight into the functional genetic basis of how phenotypically plastic traits may still be important sources of community genetic effects. PMID:21444311

Tétard-Jones, C; Kertesz, M A; Preziosi, R F

2011-05-12

111

Quantification of retinal pigment epithelial phenotypic variation using laser scanning cytometry  

PubMed Central

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.

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

2010-01-01

112

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

PubMed Central

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.

Moore, Kara A.; Stanton, Maureen L.

2014-01-01

113

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

PubMed Central

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.

Forsman, Anders

2014-01-01

114

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

PubMed

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

Forsman, Anders

2014-01-01

115

Different mechanisms underlie phenotypic plasticity and interspecific variation for a reproductive character in drosophilids (Insecta: Diptera).  

PubMed

The insect ovary is a modular structure, the functional unit of which is the ovariole. Ovariole number is positively correlated with potential reproductive output. Among drosophilids (Insecta: Diptera), ovariole number shows both phenotypic plasticity and substantial interspecific and interpopulational variation. Here we examine the mechanistic connection between phenotypic plasticity and genetically fixed variation in ovariole number within the melanogaster species group. When a laboratory population of Drosophila melanogaster was reared under reduced food conditions, differences in ovariole number were entirely due to alterations in cell differentiation during the wandering stage at the very end of larval development. Cell growth and cell death were not affected. When these same flies were reared under a variety of temperatures, ovariole number differences arose during the latter half of the third (final) larval instar. Cell differentiation was affected, although cell number was not, and ovariole number differences were established before metamorphosis. In contrast, genetically fixed, interspecific and interpopulational variability in ovariole number was caused by alterations in the dynamics of cell differentiation and by cell number differences. Furthermore, the stages affected were different in different species and populations in the melanogaster species group, ranging from the first (D. sechellia) through the middle of the third (D. simulans and D. mauritiana) larval stage. Therefore, the mechanistic bases for plasticity-based variability are largely distinct from the mechanistic bases for interspecific and interpopulational variability. Our results suggest that phenotypic plasticity indicates evolutionary flexibility in underlying ontogenetic processes. PMID:11108591

Hodin, J; Riddiford, L M

2000-10-01

116

Candidate genes and thermal phenotypes: identifying ecologically important genetic variation for thermotolerance in the Australian Drosophila melanogaster cline.  

PubMed

Clinal variation in traits often reflects climatic adaptation; in Drosophila melanogaster clinal variation provides an opportunity to link variation in chromosomal inversions, microsatellite loci and various candidate genes to adaptive variation in traits. We undertook association studies with crosses from a single population of D. melanogaster from eastern Australia to investigate the association between genetic markers and traits showing clinal variation. By genotyping parents and phenotyping offspring, we minimized genotyping costs but had the power to detect association between markers and quantitative traits. Consistent with prior studies, we found strong associations between the clinal chromosomal inversion In(3R)Payne and markers within it, as well as among these markers. We also found an association between In(3L)Payne and one marker located within this inversion. Of the five predicted associations between markers and traits, four were detected (increased heat, decreased cold resistance and body size with the heat shock gene hsr-omega S, increased cold resistance with the inversion In(3L)Payne), while one was not detected (heat resistance and the heat shock gene hsp68). In a set of eight exploratory tests, we detected one positive association (between hsp23a and heat resistance) but no associations of heat resistance with alleles at the hsp26, hsp83, Desat 2, alpha-Gpdh, hsp70 loci, while cold resistance was not associated with Frost and Dca loci. These results confirm interactions between hsr-omega and thermal resistance, as well as between In(3L)Payne and cold resistance, but do not provide evidence for associations between thermal responses and alleles at other clinically varying marker genes. PMID:17614909

Rako, Lea; Blacket, Mark J; McKechnie, Stephen W; Hoffmann, Ary A

2007-07-01

117

Quantitative genetics: a promising approach for the assessment of genetic variation in endangered species  

Microsoft Academic Search

The measurement of genetic variation is often an important component of endangered species management programs. Each of several tools available to measure genetic diversity has positive and negative attributes. Quantitative genetic techniques have not received much attention in the conservation field, yet they are likely to reveal variation that is most closely associated with components of fitness. In addition, quantitative

Andrew Storfer

1996-01-01

118

Clustering expressed genes on the basis of their association with a quantitative phenotype  

Microsoft Academic Search

Summary Cluster analyses of gene expression data are usually conducted based on their associations with the phenotype of a particular disease. Many disease traits have a clearly defined binary phenotype (presence or absence), so that genes can be clustered based on the differences of expression levels between the two contrasting phenotypic groups. For example, cluster analysis based on binary phenotype

ZHENYU JIA; SHIZHONG XU

2005-01-01

119

How closely correlated are molecular and quantitative measures of genetic variation? A meta-analysis.  

PubMed

The ability of populations to undergo adaptive evolution depends on the presence of quantitative genetic variation for ecologically important traits. Although molecular measures are widely used as surrogates for quantitative genetic variation, there is controversy about the strength of the relationship between the two. To resolve this issue, we carried out a meta-analysis based on 71 datasets. The mean correlation between molecular and quantitative measures of genetic variation was weak (r = 0.217). Furthermore, there was no significant relationship between the two measures for life-history traits (r = -0.11) or for the quantitative measure generally considered as the best indicator of adaptive potential, heritability (r = -0.08). Consequently, molecular measures of genetic diversity have only a very limited ability to predict quantitative genetic variability. When information about a population's short-term evolutionary potential or estimates of local adaptation and population divergence are required, quantitative genetic variation should be measured directly. PMID:11475045

Reed, D H; Frankham, R

2001-06-01

120

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

USGS Publications Warehouse

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.

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

1984-01-01

121

Geographical and environmental gradients shape phenotypic trait variation and genetic structure in Populus trichocarpa.  

PubMed

• Populus trichocarpa is widespread across western North America spanning extensive variation in photoperiod, growing season and climate. We investigated trait variation in P. trichocarpa using over 2000 trees from a common garden at Vancouver, Canada, representing replicate plantings of 461 genotypes originating from 136 provenance localities. • We measured 40 traits encompassing phenological events, biomass accumulation, growth rates, and leaf, isotope and gas exchange-based ecophysiology traits. With replicated plantings and 29,354 single nucleotide polymorphisms (SNPs) from 3518 genes, we estimated both broad-sense trait heritability (H(2)) and overall population genetic structure from principal component analysis. • Populus trichocarpa had high phenotypic variation and moderate/high H(2) for many traits. H(2) ranged from 0.3 to 0.9 in phenology, 0.3 to 0.8 in biomass and 0.1 to 0.8 in ecophysiology traits. Most traits correlated strongly with latitude, maximum daylength and temperature of tree origin, but not necessarily with elevation, precipitation or heat : moisture indices. Trait H(2) values reflected trait correlation strength with geoclimate variables. The population genetic structure had one significant principal component (PC1) which correlated with daylength and showed enrichment for genes relating to circadian rhythm and photoperiod. • Robust relationships between traits, population structure and geoclimate in P. trichocarpa reflect patterns which suggest that range-wide geographical and environment gradients have shaped its genotypic and phenotypic variability. PMID:24491114

McKown, Athena D; Guy, Robert D; Klápšt?, Jaroslav; Geraldes, Armando; Friedmann, Michael; Cronk, Quentin C B; El-Kassaby, Yousry A; Mansfield, Shawn D; Douglas, Carl J

2014-03-01

122

Nutritional implications of genetic taste variation: the role of PROP sensitivity and other taste phenotypes.  

PubMed

Genetic sensitivity to the bitter taste of phenylthiocarbamide and 6-n-propylthiouracil (PROP) is a well-studied human trait. It has been hypothesized that this phenotype is a marker for individual differences in taste perception that influence food preferences and dietary behavior with subsequent links to body weight and chronic disease risk. Steady progress has been made over the past several decades in defining the involvement of this phenotype and its underlying gene, TAS2R38, in this complex behavioral pathway. However, more work needs to be done to fully determine its overall nutritional and health significance. The primary goal of this review is to assess our current understanding of the role of the PROP bitter taste phenotype in food selection and body weight in both children and adults. A brief history of the field is included and controversies surrounding the use of different PROP screening methods are addressed. The contribution of other receptors (both bitter and nonbitter) to human taste variation is also discussed. PMID:18407743

Tepper, Beverly J

2008-01-01

123

Quantitative phenotyping of Duchenne muscular dystrophy dogs by comprehensive gait analysis and overnight activity monitoring.  

PubMed

The dystrophin-deficient dog is excellent large animal model for testing novel therapeutic modalities for Duchenne muscular dystrophy (DMD). Despite well-documented descriptions of dystrophic symptoms in these dogs, very few quantitative studies have been performed. Here, we developed a comprehensive set of non-invasive assays to quantify dog gait (stride length and speed), joint angle and limb mobility (for both forelimb and hind limb), and spontaneous activity at night. To validate these assays, we examined three 8-m-old mix-breed dystrophic dogs. We also included three age-matched siblings as the normal control. High-resolution video recorders were used to digitize dog walking and spontaneous movement at night. Stride speed and length were significantly decreased in affected dogs. The mobility of the limb segments (forearm, front foot, lower thigh, rear foot) and the carpus and hock joints was significantly reduced in dystrophic dogs. There was also a significant reduction of the movement in affected dogs during overnight monitoring. In summary, we have established a comprehensive set of outcome measures for clinical phenotyping of DMD dogs. These non-invasive end points would be valuable in monitoring disease progression and therapeutic efficacy in translational studies in the DMD dog model. PMID:23544107

Shin, Jin-Hong; Greer, Brian; Hakim, Chady H; Zhou, Zhongna; Chung, Yu-chia; Duan, Ye; He, Zhihai; Duan, Dongsheng

2013-01-01

124

Plasmodium falciparum Heterochromatin Protein 1 Marks Genomic Loci Linked to Phenotypic Variation of Exported Virulence Factors  

PubMed Central

Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that P. falciparum heterochromatin protein 1 (PfHP1) binds specifically to H3K9me3 but not to other repressive histone methyl marks. Based on nuclear fractionation and detailed immuno-localization assays, PfHP1 constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with virulence gene arrays in subtelomeric and chromosome-internal islands and a high correlation with previously mapped H3K9me3 marks. These include not only var genes, but also the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host–parasite interactions. In addition, we identified a number of PfHP1-bound genes that were not enriched in H3K9me3, many of which code for proteins expressed during invasion or at different life cycle stages. Interestingly, PfHP1 is absent from centromeric regions, implying important differences in centromere biology between P. falciparum and its human host. Over-expression of PfHP1 results in an enhancement of variegated expression and highlights the presence of well-defined heterochromatic boundaries. In summary, we identify PfHP1 as a major effector of virulence gene silencing and phenotypic variation. Our results are instrumental for our understanding of this widely used survival strategy in unicellular pathogens.

Volz, Jennifer; Niederwieser, Igor; Salcedo-Amaya, Adriana M.; Alako, Blaise T. F.; Ehlgen, Florian; Ralph, Stuart A.; Cowman, Alan F.; Bozdech, Zbynek; Stunnenberg, Hendrik G.; Voss, Till S.

2009-01-01

125

Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.  

PubMed

Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that P. falciparum heterochromatin protein 1 (PfHP1) binds specifically to H3K9me3 but not to other repressive histone methyl marks. Based on nuclear fractionation and detailed immuno-localization assays, PfHP1 constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with virulence gene arrays in subtelomeric and chromosome-internal islands and a high correlation with previously mapped H3K9me3 marks. These include not only var genes, but also the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host-parasite interactions. In addition, we identified a number of PfHP1-bound genes that were not enriched in H3K9me3, many of which code for proteins expressed during invasion or at different life cycle stages. Interestingly, PfHP1 is absent from centromeric regions, implying important differences in centromere biology between P. falciparum and its human host. Over-expression of PfHP1 results in an enhancement of variegated expression and highlights the presence of well-defined heterochromatic boundaries. In summary, we identify PfHP1 as a major effector of virulence gene silencing and phenotypic variation. Our results are instrumental for our understanding of this widely used survival strategy in unicellular pathogens. PMID:19730695

Flueck, Christian; Bartfai, Richard; Volz, Jennifer; Niederwieser, Igor; Salcedo-Amaya, Adriana M; Alako, Blaise T F; Ehlgen, Florian; Ralph, Stuart A; Cowman, Alan F; Bozdech, Zbynek; Stunnenberg, Hendrik G; Voss, Till S

2009-09-01

126

Structural Basis of Quantitative Variation in Nuclear DNA  

Microsoft Academic Search

RECENT surveys show that variation in the amount of nuclear DNA, quite independently of change in chromosome number, is frequently associated with the divergence and evolution of both plant and animal species1-10. The extent of such variation is often very great, particularly among the angiosperms. One of the many problems posed by these findings is the nature of the chromosome

H. Rees; R. N. Jones

1967-01-01

127

Quantitative trait loci affecting natural variation in Drosophila longevity  

Microsoft Academic Search

Limited life span and senescence are universal phenomena, controlled by genetic and environmental factors whose interactions both limit life span and generate variation in life span between individuals, populations and species. To understand the genetic architecture of longevity it is necessary to know what loci affect variation in life span, what are the allelic effects at these loci and what

Gretchen L Geiger-Thornsberry; Trudy F. C Mackay

2004-01-01

128

Human genetic variation within neural crest enhancers: molecular and phenotypic implications.  

PubMed

Developmental gene expression programmes are coordinated by the specialized distal cis-regulatory elements called enhancers, which integrate lineage- and signalling-dependent inputs to guide morphogenesis. In previous work, we characterized the genome-wide repertoire of active enhancers in human neural crest cells (hNCC), an embryonic cell population with critical roles in craniofacial development. We showed that in hNCC, co-occupancy of a master regulator TFAP2A with nuclear receptors NR2F1 and NR2F2 correlates with the presence of permissive enhancer chromatin states. Here, we take advantage of pre-existing human genetic variation to further explore potential cooperation between TFAP2A and NR2F1/F2. We demonstrate that isolated single nucleotide polymorphisms affecting NR2F1/F2-binding sites within hNCC enhancers can alter TFAP2A occupancy and overall chromatin features at the same enhancer allele. We propose that a similar strategy can be used to elucidate other cooperative relationships between transcription factors involved in developmental transitions. Using the neural crest and its major contribution to human craniofacial phenotypes as a paradigm, we discuss how genetic variation might modulate the molecular properties and activity of enhancers, and ultimately impact human phenotypic diversity. PMID:23650634

Rada-Iglesias, Alvaro; Prescott, Sara L; Wysocka, Joanna

2013-01-01

129

Selective sweep at a quantitative trait locus in the presence of background genetic variation.  

PubMed

We model selection at a locus affecting a quantitative trait (QTL) in the presence of genetic variance due to other loci. The dynamics at the QTL are related to the initial genotypic value and to the background genetic variance of the trait, assuming that background genetic values are normally distributed, under three different forms of selection on the trait. Approximate dynamics are derived under the assumption of small mutation effect. For similar strengths of selection on the trait (i.e, gradient of directional selection beta) the way background variation affects the dynamics at the QTL critically depends on the shape of the fitness function. It generally causes the strength of selection on the QTL to decrease with time. The resulting neutral heterozygosity pattern resembles that of a selective sweep with a constant selection coefficient corresponding to the early conditions. The signature of selection may also be blurred by mutation and recombination in the later part of the sweep. We also study the race between the QTL and its genetic background toward a new optimum and find the conditions for a complete sweep. Overall, our results suggest that phenotypic traits exhibiting clear-cut molecular signatures of selection may represent a biased subset of all adaptive traits. PMID:18832353

Chevin, Luis-Miguel; Hospital, Frédéric

2008-11-01

130

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

Microsoft Academic Search

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

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

1993-01-01

131

Quantifying Phenotypic Variation in Isogenic Caenorhabditis elegans Expressing Phsp-16.2::gfp by Clustering 2D Expression Patterns  

Microsoft Academic Search

Isogenic populations of animals still show a surprisingly large amount of phenotypic variation between individuals. Using a GFP reporter that has been shown to predict longevity and resistance to stress in isogenic populations of the nematode Caenorhabditis elegans, we examined residual variation in expression of this GFP reporter. We found that when we separated the populations into brightest 3% and

Alexander K. Seewald; James Cypser; Alexander Mendenhall; Thomas Johnson; Johannes Jaeger

2010-01-01

132

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

SciTech Connect

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.

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

1997-02-01

133

Patterns of quantitative genetic variation in multiple dimensions.  

PubMed

A fundamental question for both evolutionary biologists and breeders is the extent to which genetic correlations limit the ability of populations to respond to selection. Here I view this topic from three perspectives. First, I propose several nondimensional statistics to quantify the genetic variation present in a suite of traits and to describe the extent to which correlations limit their selection response. A review of five data sets suggests that the total variation differs substantially between populations. In all cases analyzed, however, the "effective number of dimensions" is less than two: more than half of the total genetic variation is explained by a single combination of traits. Second, I consider how patterns of variation affect the average evolutionary response to selection in a random direction. When genetic variation lies in a small number of dimensions but there are a large number of traits under selection, then the average selection response will be reduced substantially from its potential maximum. Third, I discuss how a low genetic correlation between male fitness and female fitness limits the ability of populations to adapt. Data from two recent studies of natural populations suggest this correlation can diminish or even erase any genetic benefit to mate choice. Together these results suggest that adaptation (in natural populations) and genetic improvement (in domesticated populations) may often be as much constrained by patterns of genetic correlation as by the overall amount of genetic variation. PMID:18695991

Kirkpatrick, Mark

2009-06-01

134

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

PubMed Central

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.

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

135

Predicting quantitative variation within rice germplasm using molecular markers  

Microsoft Academic Search

Diverse Asian rice (Oryza sativa) germplasm has been used to identify associations between various quantitative traits and RAPD molecular markers using multiple regression analysis. This has allowed us to predict for other samples of germplasm their performance for traits such as culm length and number, days to flowering, grain width, and panicle and leaf length using only RAPD marker data.

Parminder S Virk; Brian V Ford-Lloyd; Michael T Jackson; Harpal S Pooni; Tomas P Clemeno; H John Newbury

1996-01-01

136

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

PubMed Central

Background Since 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 Pregnancy Outcome (HAPO) cohort, a large multiethnic multicenter study designed to address the impact of glycemia less than overt diabetes on pregnancy outcome. Results Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c levels were measured in blood samples obtained from HAPO participants during an oral glucose tolerance test at 24-32 weeks gestation. We tested for association between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04% increase per allele C; p-value?=?4.4×10?5), RETN and fasting plasma glucose (rs1423096; 0.7 mg/dl decrease per allele A; p-value?=?1.1×10?4), IL8 and 1 hr plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value?=?1.3×10?4), ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p-value?=?1.4×10?4), LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per allele T; p-value?=?2.4×10?4), and IL6 and 1-hour plasma glucose (rs6954897; ?2.29 mg/dl decrease per allele G, p-value?=?4.3×10?4). Conclusions Based on the genes surveyed in this study the inflammatory pathway is unlikely to have a strong impact on maternal metabolic phenotypes in pregnancy although variation in individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF alpha,) may contribute to metabolic phenotypes in pregnant women.

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

2012-01-01

137

Variation at range margins across multiple spatial scales: environmental temperature, population genetics and metabolomic phenotype  

PubMed Central

Range margins are spatially complex, with environmental, genetic and phenotypic variations occurring across a range of spatial scales. We examine variation in temperature, genes and metabolomic profiles within and between populations of the subalpine perennial plant Arabidopsis lyrata ssp. petraea from across its northwest European range. Our surveys cover a gradient of fragmentation from largely continuous populations in Iceland, through more fragmented Scandinavian populations, to increasingly widely scattered populations at the range margin in Scotland, Wales and Ireland. Temperature regimes vary substantially within some populations, but within-population variation represents a larger fraction of genetic and especially metabolomic variances. Both physical distance and temperature differences between sites are found to be associated with genetic profiles, but not metabolomic profiles, and no relationship was found between genetic and metabolomic population structures in any region. Genetic similarity between plants within populations is the highest in the fragmented populations at the range margin, but differentiation across space is the highest there as well, suggesting that regional patterns of genetic diversity may be scale dependent.

Kunin, William E.; Vergeer, Philippine; Kenta, Tanaka; Davey, Matthew P.; Burke, Terry; Ian Woodward, F.; Quick, Paul; Mannarelli, Maria-Elena; Watson-Haigh, Nathan S.; Butlin, Roger

2009-01-01

138

A Quantitative Investigation of Stakeholder Variation in Training Program Evaluation.  

ERIC Educational Resources Information Center

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…

Michalski, Greg V.

139

QUANTITATIVE IMAGE ANALYSIS TECHNIQUE FOR DETERMINING LOCAL DENSITY VARIATION  

Microsoft Academic Search

The PMPA Standards Committee is developing a new test method for determining the porosity of powder metallurgy products by image analysis techniques. This technique would be used to evaluate the local density variation in complex P\\/M parts. An inter-laboratory study was conducted to estimate the uncertainty of this new measurement technique. The results found the accuracy of the test method

Howard I. Sanderow; Tom Murphy

140

Tolerance of Lolium hybrids to quantitative variation in nuclear DNA  

Microsoft Academic Search

THE genus Lolium contains six species, all diploids with 14 chromosomes. The chromosomes of the inbreeding species are larger than those of the outbreeders and carry about 30% more DNA1. Although the range of variation in nuclear DNA amount is not large, in comparison with other genera of flowering plants2, Lolium is exceptional in that crosses between diploid species with

P. K. Gupta; H. Rees

1975-01-01

141

Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation  

PubMed Central

Background Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. Results We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0?1%. Conclusions Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.

Lee, Soohyun; Kasif, Simon; Weng, Zhiping; Cantor, Charles R.

2008-01-01

142

Quantitative genetic modeling of variation in human brain morphology  

Microsoft Academic Search

The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high

W. F. C. Baare; H. E. Hulshoff-Poll; Dorret I. Boomsma; Daniëlle Posthuma; Geus de E. J. C; H. G. Snack; Haren van N. E. M; Oel van C. J; René S. Kahn

2001-01-01

143

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

PubMed

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

Abrams, Marc D.

1994-01-01

144

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

PubMed

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

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

2014-08-01

145

Mathematical Learning Disabilities in Special Populations: Phenotypic Variation and Cross-Disorder Comparisons  

PubMed Central

What is mathematical learning disability (MLD)? The reviews in this special issue adopt different approaches to defining the construct of MLD. Collectively, they demonstrate the current status of efforts to establish a consensus definition and the challenges faced in this endeavor. In this commentary, we reflect upon the proposed pathways to mathematical learning difficulties and disabilities presented across the reviews. Specifically we consider how each of the reviews contributes to identifying the MLD phenotype by specifying the range of assets and deficits in mathematics, identifying sources of individual variation, and characterizing the natural progression of MLD over the life course. We show how principled comparisons across disorders address issues about the cognitive and behavioral co-morbidities of MLD, and whether commonalities in brain dysmorphology are associated with common mathematics performance profiles. We project the status of MLD research ten years hence with respect to theoretical gains, advances in methodology, and principled intervention studies.

Dennis, Maureen; Berch, Daniel B.; Mazzocco, Michele M.M.

2011-01-01

146

Mathematical learning disabilities in special populations: phenotypic variation and cross-disorder comparisons.  

PubMed

What is mathematical learning disability (MLD)? The reviews in this special issue adopt different approaches to defining the construct of MLD. Collectively, they demonstrate the current status of efforts to establish a consensus definition and the challenges faced in this endeavor. In this commentary, we reflect upon the proposed pathways to mathematical learning difficulties and disabilities presented across the reviews. Specifically we consider how each of the reviews contributes to identifying the MLD phenotype by specifying the range of assets and deficits in mathematics, identifying sources of individual variation, and characterizing the natural progression of MLD over the life course. We show how principled comparisons across disorders address issues about the cognitive and behavioral co-morbidities of MLD, and whether commonalities in brain dysmorphology are associated with common mathematics performance profiles. We project the status of MLD research ten years hence with respect to theoretical gains, advances in methodology, and principled intervention studies. PMID:19213019

Dennis, Maureen; Berch, Daniel B; Mazzocco, Michèle M M

2009-01-01

147

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

Microsoft Academic Search

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

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

2003-01-01

148

Quantitative genetic variation in the hematopoietic stem cell and progenitor cell compartment and in lifespan are closely linked at multiple loci in BXD recombinant inbred mice.  

PubMed

The number of bone marrow hematopoietic stem and progenitor cells as defined by the lineage(-), Sca1(++), c-kit(+) (LSK) phenotype and their proliferative capacity in vitro are subject to quantitative genetic variation, and several quantitative trait loci (QTL) have been identified in young mice. Because some traits affecting hematopoiesis also change with age in a mouse strain-dependent fashion, we performed quantitative trait analysis in aged BXD recombinant inbred (RI) mice for the number and frequency of LSK cells, and for their proliferative capacity in vitro. Several novel QTL were identified. The number and frequency of LSK cells in old mice correlated inversely with lifespan. Furthermore, 4 of 7 lifespan QTL overlap with QTL contributing to the number, frequency, or proliferative capacity of LSK cells in young or old mice. Taken together, these data establish a close genetic, and perhaps functional, link between genetic variation in lifespan and characteristics of stem and progenitor cells. PMID:14988159

Henckaerts, Els; Langer, Jessica C; Snoeck, Hans-Willem

2004-07-15

149

Genetic and Phenotypic Variations of a Resistant Pseudomonas aeruginosa Epidemic Clone  

PubMed Central

From May 1997 to December 2001, a serotype O:6 multidrug-resistant strain of Pseudomonas aeruginosa colonized or infected 201 patients in the University Hospital of Besançon (France). The susceptibility profile of this epidemic clone to fluoroquinolones and aminoglycosides was relatively stable during the outbreak but showed important isolate-to-isolate variations (up to 64-fold) in the MICs of ?-lactams. Analysis of 18 genotypically related isolates selected on a quaterly basis demonstrated alterations in the two DNA topoisomerases II and IV (Thr83?Ile in GyrA and Ser87?Leu in ParC) and production of an ANT(2")-I enzyme. Although constitutively overproduced in these bacteria, the MexXY efflux system did not appear to contribute significantly to aminoglycoside resistance. ?-Lactam resistance was associated with derepression of intrinsic AmpC ?-lactamase (with isolate-to-isolate variations of up to 58-fold) and sporadic deficiency in a 46-kDa protein identified as the carbapenem-selective porin OprD. Of the 18 isolates, 14 were also found to overproduce the efflux system MexAB-OprM as a result of alteration of the repressor protein MexR (His107?Pro). However, complementation experiments with the cloned mexR gene demonstrated that MexAB-OprM contributed only marginally to ?-lactam and fluoroquinolone resistance. Of the four isolates exhibiting wild-type MexAB-OprM expression despite the MexR alteration, two appeared to harbor secondary mutations in the mexA-mexR intergenic region and one harbored secondary mutations in the putative ribosome binding site located upstream of the mexAB oprM operon. In conclusion, this study shows that many mechanisms were involved in the multiresistance phenotype of this highly epidemic strain of P. aeruginosa. Our results also demonstrate that the clone sporadically underwent substantial genetic and phenotypic variations during the course of the outbreak, perhaps in relation to local or individual selective drug pressures.

Hocquet, Didier; Bertrand, Xavier; Kohler, Thilo; Talon, Daniel; Plesiat, Patrick

2003-01-01

150

recA mediated spontaneous deletions of the icaADBC operon of clinical Staphylococcus epidermidis isolates: a new mechanism of phenotypic variations  

Microsoft Academic Search

Phenotypic variation of Staphylococcus epidermidis involving the slime related ica operon results in heterogeneity in surface characteristics of individual bacteria in axenic cultures. Five clinical S. epidermidis isolates demonstrated phenotypic variation, i.e. both black and red colonies on Congo Red agar. Black colonies displayed\\u000a bi-modal electrophoretic mobility distributions at pH 2, but such phenotypic variation was absent in red colonies

Titik Nuryastuti; Henny C. van der Mei; Henk J. Busscher; Roel Kuijer; Abu T. Aman; Bastiaan P. Krom

2008-01-01

151

Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.  

PubMed

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population. PMID:19342699

Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

2010-01-01

152

Pleiotropic model of maintenance of quantitative genetic variation at mutation-selection balance.  

PubMed

A pleiotropic model of maintenance of quantitative genetic variation at mutation-selection balance is investigated. Mutations have effects on a metric trait and deleterious effects on fitness, for which a bivariate gamma distribution is assumed. Equations for calculating the strength of apparent stabilizing selection (V(s)) and the genetic variance maintained in segregating populations (V(G)) were derived. A large population can hold a high genetic variance but the apparent stabilizing selection may or may not be relatively strong, depending on other properties such as the distribution of mutation effects. If the distribution of mutation effects on fitness is continuous such that there are few nearly neutral mutants, or a minimum fitness effect is assumed if most mutations are nearly neutral, V(G) increases to an asymptote as the population size increases. Both V(G) and V(s) are strongly affected by the shape of the distribution of mutation effects. Compared with mutants of equal effect, allowing their effects on fitness to vary across loci can produce a much higher V(G) but also a high V(s) (V(s) in phenotypic standard deviation units, which is always larger than the ratio V(P)/V(m)), implying weak apparent stabilizing selection. If the mutational variance V(m) is approximately 10(-3)V(e) (V(e), environmental variance), the model can explain typical values of heritability and also apparent stabilizing selection, provided the latter is quite weak as suggested by a recent review. PMID:12019255

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

2002-05-01

153

Comparative losses of quantitative and molecular genetic variation in finite populations of Drosophila melanogaster.  

PubMed

Quantitative genetic variation, the main determinant of the ability to evolve, is expected to be lost in small populations, but there are limited data on the effect, and controversy as to whether it is similar to that for near neutral molecular variation. Genetic variation for abdominal and sternopleural bristle numbers and allozyme heterozygosity were estimated in 23 populations of Drosophila melanogaster maintained at effective population sizes of 25, 50, 100, 250 or 500 for 50 generations, as well as in 19 highly inbred populations and the wild outbred base population. Highly significant negative regressions of proportion of initial genetic variation retained on inbreeding due to finite population size were observed for both quantitative characters (b = -0.67 +/- 0.14 and -0.58 +/- 0.11) and allozyme heterozygosity (b = -0.79 +/- 0.10), and the regression coefficients did not differ significantly. Thus, quantitative genetic variation is being lost at a similar rate to molecular genetic variation. However, genetic variation for all traits was lost at rates significantly slower than predicted by neutral theory, most likely due to associative overdominance. Positive, but relatively low correlations were found among the different measures of genetic variation, but their low magnitudes were attributed to large sampling errors, rather than differences in the underlying processes of loss. PMID:16089035

Gilligan, Dean M; Briscoe, David A; Frankham, Richard

2005-02-01

154

Quantitative multi-parametric evaluation of centrosome declustering drugs: centrosome amplification, mitotic phenotype, cell cycle and death.  

PubMed

Unlike normal cells, cancer cells contain amplified centrosomes and rely on centrosome clustering mechanisms to form a pseudobipolar spindle that circumvents potentially fatal spindle multipolarity (MP). Centrosome clustering also promotes low-grade chromosome missegregation, which can drive malignant transformation and tumor progression. Putative 'centrosome declustering drugs' represent a cancer cell-specific class of chemotherapeutics that produces a common phenotype of centrosome declustering and spindle MP. However, differences between individual agents in terms of efficacy and phenotypic nuances remain unexplored. Herein, we have developed a conceptual framework for the quantitative evaluation of centrosome declustering drugs by investigating their impact on centrosomes, clustering, spindle polarity, cell cycle arrest, and death in various cancer cell lines at multiple drug concentrations over time. Surprisingly, all centrosome declustering drugs evaluated in our study were also centrosome-amplifying drugs to varying extents. Notably, all declustering drugs induced spindle MP, and the peak extent of MP positively correlated with the induction of hypodiploid DNA-containing cells. Our data suggest acentriolar spindle pole amplification as a hitherto undescribed activity of some declustering drugs, resulting in spindle MP in cells that may not have amplified centrosomes. In general, declustering drugs were more toxic to cancer cell lines than non-transformed ones, with some exceptions. Through a comprehensive description and quantitative analysis of numerous phenotypes induced by declustering drugs, we propose a novel framework for the assessment of putative centrosome declustering drugs and describe cellular characteristics that may enhance susceptibility to them. PMID:24787016

Ogden, A; Cheng, A; Rida, P C G; Pannu, V; Osan, R; Clewley, R; Aneja, R

2014-01-01

155

Quantitative multi-parametric evaluation of centrosome declustering drugs: centrosome amplification, mitotic phenotype, cell cycle and death  

PubMed Central

Unlike normal cells, cancer cells contain amplified centrosomes and rely on centrosome clustering mechanisms to form a pseudobipolar spindle that circumvents potentially fatal spindle multipolarity (MP). Centrosome clustering also promotes low-grade chromosome missegregation, which can drive malignant transformation and tumor progression. Putative ‘centrosome declustering drugs' represent a cancer cell-specific class of chemotherapeutics that produces a common phenotype of centrosome declustering and spindle MP. However, differences between individual agents in terms of efficacy and phenotypic nuances remain unexplored. Herein, we have developed a conceptual framework for the quantitative evaluation of centrosome declustering drugs by investigating their impact on centrosomes, clustering, spindle polarity, cell cycle arrest, and death in various cancer cell lines at multiple drug concentrations over time. Surprisingly, all centrosome declustering drugs evaluated in our study were also centrosome-amplifying drugs to varying extents. Notably, all declustering drugs induced spindle MP, and the peak extent of MP positively correlated with the induction of hypodiploid DNA-containing cells. Our data suggest acentriolar spindle pole amplification as a hitherto undescribed activity of some declustering drugs, resulting in spindle MP in cells that may not have amplified centrosomes. In general, declustering drugs were more toxic to cancer cell lines than non-transformed ones, with some exceptions. Through a comprehensive description and quantitative analysis of numerous phenotypes induced by declustering drugs, we propose a novel framework for the assessment of putative centrosome declustering drugs and describe cellular characteristics that may enhance susceptibility to them.

Ogden, A; Cheng, A; Rida, P C G; Pannu, V; Osan, R; Clewley, R; Aneja, R

2014-01-01

156

The adaptedness of the floral phenotype in a relict endemic, hawkmoth-pollinated violet. 1. Reproductive correlates of floral variation  

Microsoft Academic Search

This paper examines the relationship between quantitative variation in floral morphology (sizes of petals, spur and peduncle) and maternal reproductive success (seed production) in Viola cazorlensic (Violaceae), a narrowly endemic violet of south-eastern Spain pollinated by day-flying hawkmoths (Sphingidae). This plant is characterized by broad intraspecific variation in size and proportions of floral parts. Floral morphology does not influence significantly

CARLOS M. HERRERA

1990-01-01

157

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

PubMed Central

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.

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

2014-01-01

158

High-throughput phenotypic profiling of gene-environment interactions by quantitative growth curve analysis in Saccharomyces cerevisiae.  

PubMed

Cell-based assays are widely used in high-throughput screening to determine the effects of toxicants and drugs on their biological targets. To enable a functional genomics modeling of gene-environment interactions, quantitative assays are required both for gene expression and for the phenotypic responses to environmental challenge. To address this need, we describe an automated high-throughput methodology that provides phenotypic profiling of the cellular responses to environmental stress in Saccharomyces cerevisiae. Standardized assay conditions enable the use of a single metric value to quantify yeast microculture growth curves. This assay format allows precise control of both genetic and environmental determinants of the cellular responses to oxidative stress, a common mechanism of environmental insult. These yeast-cell-based assays are validated with hydrogen peroxide, a simple direct-acting oxidant. Phenotypic profiling of the oxidative stress response of a yap1 mutant strain demonstrates the mechanistic analysis of genetic susceptibility to oxidative stress. As a proof of concept for analysis of more complex gene-environment interactions, we describe a combinatorial assay design for phenotypic profiling of the cellular responses to tert-butyl hydroperoxide, a complex oxidant that is actively metabolized by its target cells. Thus, the yeast microculture assay format supports comprehensive applications in toxicogenomics. PMID:15033507

Weiss, Andrew; Delproposto, James; Giroux, Craig N

2004-04-01

159

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

PubMed Central

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.

Esberg, Anders; Lofgren-Burstrom, Anna; Ohman, Ulla

2012-01-01

160

Somatic hybrids produced by protoplast fusion between S. tuberosum and S. brevidens: phenotypic variation under field conditions  

Microsoft Academic Search

Phenotypic and flowering characteristics of hybrid plants generated by protoplast fusion between a tetraploid S. tuberosum line and diploid S. brevidens were assessed under field conditions. Hybrids were compared to both clonal parental material and protoplast-derived plants of each parent. Almost all of the hybrids were hexaploid. A wide range of variation in morphological characters was observed for hybrids and

S. Austin; M. K. Ehlenfeldt; M. A. Baer; J. P. Helgeson

1986-01-01

161

Mouse genomic variation and its effect on phenotypes and gene regulation.  

PubMed

We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism. PMID:21921910

Keane, Thomas M; Goodstadt, Leo; Danecek, Petr; White, Michael A; Wong, Kim; Yalcin, Binnaz; Heger, Andreas; Agam, Avigail; Slater, Guy; Goodson, Martin; Furlotte, Nicholas A; Eskin, Eleazar; Nellåker, Christoffer; Whitley, Helen; Cleak, James; Janowitz, Deborah; Hernandez-Pliego, Polinka; Edwards, Andrew; Belgard, T Grant; Oliver, Peter L; McIntyre, Rebecca E; Bhomra, Amarjit; Nicod, Jérôme; Gan, Xiangchao; Yuan, Wei; van der Weyden, Louise; Steward, Charles A; Bala, Sendu; Stalker, Jim; Mott, Richard; Durbin, Richard; Jackson, Ian J; Czechanski, Anne; Guerra-Assunção, José Afonso; Donahue, Leah Rae; Reinholdt, Laura G; Payseur, Bret A; Ponting, Chris P; Birney, Ewan; Flint, Jonathan; Adams, David J

2011-09-15

162

Mouse genomic variation and its effect on phenotypes and gene regulation  

PubMed Central

We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism.

Keane, Thomas M.; Goodstadt, Leo; Danecek, Petr; White, Michael A.; Wong, Kim; Yalcin, Binnaz; Heger, Andreas; Agam, Avigail; Slater, Guy; Goodson, Martin; Furlotte, Nicholas A.; Eskin, Eleazar; Nellaker, Christoffer; Whitley, Helen; Cleak, James; Janowitz, Deborah; Hernandez-Pliego, Polinka; Edwards, Andrew; Belgard, T. Grant; Oliver, Peter L.; McIntyre, Rebecca E.; Bhomra, Amarjit; Nicod, Jerome; Gan, Xiangchao; Yuan, Wei; van der Weyden, Louise; Steward, Charles A.; Balasubramaniam, Sendu; Stalker, Jim; Mott, Richard; Durbin, Richard; Jackson, Ian J.; Czechanski, Anne; Assuncao, Jose Afonso Guerra; Donahue, Leah Rae; Reinholdt, Laura G.; Payseur, Bret A.; Ponting, Chris P.; Birney, Ewan; Flint, Jonathan; Adams, David J.

2012-01-01

163

Quantitative Founder-Effect Analysis of French Canadian Families Identifies Specific Loci Contributing to Metabolic Phenotypes of Hypertension  

PubMed Central

The Saguenay–Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.

Hamet, P.; Merlo, E.; Seda, O.; Broeckel, U.; Tremblay, J.; Kaldunski, M.; Gaudet, D.; Bouchard, G.; Deslauriers, B.; Gagnon, F.; Antoniol, G.; Pausova, Z.; Labuda, M.; Jomphe, M.; Gossard, F.; Tremblay, G.; Kirova, R.; Tonellato, P.; Orlov, S. N.; Pintos, J.; Platko, J.; Hudson, T. J.; Rioux, J. D.; Kotchen, T. A.; Cowley, A. W.

2005-01-01

164

An Image Informatics Method for Automated Quantitative Analysis of Phenotype Visual Similarities  

PubMed Central

The post genomic era introduced the need to define single gene functions within biological pathways. A systems biology approach can be realized by automating image acquisition and phenotype classification. While machinery for automated data acquisition have been developing rapidly in the past years, the main bottleneck remains the effectiveness of the computer vision algorithms. Here we describe a fully automated process for finding phenotype similarities within a dataset acquired from an RNAi screen. The source code for the algorithms is available for free download.

Shamir, Lior; Eckley, D. Mark; Delaney, John; Orlov, Nikita; Goldberg, Ilya G.

2010-01-01

165

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

PubMed Central

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.

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

2013-01-01

166

Natural variation in CDC28 underlies morphological phenotypes in an environmental yeast isolate.  

PubMed

Morphological differences among individuals in a species represent one of the most striking aspects of biology, and a primary aim of modern genetics is to uncover the molecular basis of morphological variation. In a survey of meiosis phenotypes among environmental isolates of Saccharomyces cerevisiae, we observed an unusual arrangement of meiotic spores within the spore sac in a strain from Ivory Coast, West Africa. We mined population genomic data to identify CDC28 as the major genetic determinant of meiotic and budding cell shape behaviors in this strain. Molecular genetic methods confirmed the role of the Ivory Coast variant of CDC28 in the arrangement of spores after meiosis, in the shape of budding cells in rich medium and in the morphology of filamentous growth during nitrogen limitation. Our results shed new light on the role of CDC28 in yeast cell division, and our work suggests that with the growing availability of genomic data sets in many systems, a priori prediction of functional variants will become an increasingly powerful strategy in molecular genetics. PMID:21527779

Lee, Hana N; Magwene, Paul M; Brem, Rachel B

2011-07-01

167

Associations between environmental stress, selection history, and quantitative genetic variation in Drosophila melanogaster.  

PubMed

Stressful environments may increase quantitative genetic variation in populations by promoting the expression of genetic variation that has not previously been eliminated or canalized by natural selection. This "selection history" hypothesis predicts that novel stressors will increase quantitative genetic variation, and that the magnitude of this effect will decrease following continued stress exposure. We tested these predictions using Drosophila melanogaster and sternopleural bristle number as a model system. In particular, we examined the effect of high temperature stress (31 degrees Celsius) on quantitative genetic variation before and after our study population had been reared at 31 degrees Celsius for 15 generations. High temperature stress was found to increase both additive genetic variance and heritability, but contrary to the selection history hypothesis prediction, the magnitude of this effect significantly increased after the study population had been reared for 15 generations under high temperature stress. These results demonstrate that high temperature stress increases quantitative genetic variation for bristle number, but do not support the selection history hypothesis as an explanation for this effect. PMID:16850235

Swindell, William R; Bouzat, Juan L

2006-05-01

168

[Spontaneous mutation variation (quantitative manifestation) of some traits of the garden rose].  

PubMed

Quantitative variability of four traits (anthocyan coloration, flower aroma, double-flowering capacity, and a flower size) in spontaneous gemmacous mutants (sports) of garden rose may be not accidental but preferably orientated to the increase or decrease in the trait manifestation in the case of transaggressive inheritance by initial hybrid forms of the increased or decreased level of these traits in parents. Revealing this regularity enabled us to evolve a hypothesis explaining the decrease or increase in trait quantitative manifestation in sports by inactivation or elimination resulting from mutations in dominant alleles of the polymer genes responsible either for increasing or decreasing in phenotypic expression. Thus, if the parents of an initial form are known, it is possible to forecast in what way the quantitative characters in somatic mutants of the initial form will change, accidentally or getting preferably higher or lower. PMID:12379016

Zykov, K I

2002-01-01

169

Heritability and Phenotypic Variation of Canine Hip Dysplasia Radiographic Traits in a Cohort of Australian German Shepherd Dogs  

PubMed Central

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14–0.24 (ordinal models), 0.14–0.25 (linear models) and 0.12–0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30±0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.

Wilson, Bethany J.; Nicholas, Frank W.; James, John W.; Wade, Claire M.; Tammen, Imke; Raadsma, Herman W.; Castle, Kao; Thomson, Peter C.

2012-01-01

170

The ability of Aneurinibacillus migulanus (Bacillus brevis) to produce the antibiotic gramicidin S is correlated with phenotype variation.  

PubMed

Phenotype instability of bacterial strains can cause significant problems in biotechnological applications, since industrially useful properties may be lost. Here we report such degenerative dissociation for Aneurinibacillus migulanus (formerly known as Bacillus brevis) an established producer of the antimicrobial peptide gramicidin S (GS). Phenotypic variations within and between various strains maintained in different culture collections are demonstrated. The type strain, ATCC 9999, consists of six colony morphology variants, R, RC, RP, RT, SC, and SP, which were isolated and characterized as pure cultures. Correlations between colony morphology, growth, GS production, spore formation, and resistance to their own antimicrobial peptide were established in this study. We found the original R form to be the best producer, followed by RC, RP, and RT, while SC and SP yielded no GS at all. Currently available ATCC 9999(T) contains only 2% of the original R producer and is dominated by the newly described phenotypes RC and RP. No original R form is detected in the nominally equivalent strain DSM 2895(T) (=ATCC 9999(T)), which grows only as SC and SP phenotypes and has thus completely lost its value as a peptide producer. Two other strains from the same collection, DSM 5668 and DSM 5759, contain the unproductive SC variant and the GS-producing RC form, respectively. We describe the growth and maintenance conditions that stabilize certain colony phenotypes and reduce the degree of degenerative dissociation, thus providing a recommendation for how to revert the nonproducing smooth phenotypes to the valuable GS-producing rough ones. PMID:17720841

Berditsch, Marina; Afonin, Sergii; Ulrich, Anne S

2007-10-01

171

Using whole-genome sequence data to predict quantitative trait phenotypes in Drosophila melanogaster.  

PubMed

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

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

172

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

PubMed Central

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.

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

173

Quantitative measurements of localized density variations in cylindrical tablets using X-ray microtomography  

Microsoft Academic Search

Direct compaction is a complex process that results in a density distribution inside the tablets which is often heterogeneous. Therefore, the density variations may affect the compact properties. A quantitative analysis of this phenomenon is still lacking. Recently, X-ray microtomography has been successfully used in pharmaceutical development to study qualitatively the impact of tablet shape and break-line in the density

Virginie Busignies; Bernard Leclerc; Patrice Porion; Pierre Evesque; Guy Couarraze; Pierre Tchoreloff

2006-01-01

174

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

Microsoft Academic Search

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

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

1985-01-01

175

The effect of hypoxia on facial shape variation and disease phenotypes in chicken embryos.  

PubMed

Craniofacial anomalies can arise from both genetic and environmental factors, including prenatal hypoxia. Recent clinical evidence correlates hypoxia to craniofacial malformations. However, the mechanisms by which hypoxia mediates these defects are not yet understood. We examined the cellular mechanisms underlying malformations induced by hypoxia using a chicken (Gallus gallus) embryo model. Eggs were incubated in either hypoxic (7, 9, 11, 13, 15, 17 or 19% O2) or normoxic (21% O2) conditions. Embryos were photographed for morphological analysis at days 3-6. For analysis of skeletal development, 13-day embryos were cleared and stained with alcian blue and alizarin red for cartilage and bone, respectively. Quantitative analysis of facial shape variation was performed on images of embryos via geometric morphometrics. Early-stage embryos (day 2) were analyzed for apoptosis via whole-mount and section TUNEL staining and immunostaining for cleaved caspase-3, whereas later-stage embryos (days 4-6) were sectioned in paraffin for analysis of cell proliferation (BrdU), apoptosis (TUNEL) and metabolic stress (phospho-AMPK). Results demonstrate that survival is reduced in a dose-dependent manner. Hypoxic embryos displayed a spectrum of craniofacial anomalies, from mild asymmetry and eye defects to more severe frontonasal and cephalic anomalies. Skull bone development was delayed in hypoxic embryos, with some skeletal defects observed. Morphometric analysis showed facial shape variation relative to centroid size and age in hypoxic groups. Hypoxia disrupted cell proliferation and, in early-stage embryos, caused apoptosis of neural crest progenitor cells. Hypoxic embryos also displayed an increased metabolic stress response. These results indicate that hypoxia during early embryonic craniofacial development might induce cellular oxidative stress, leading to apoptosis of the neural crest progenitor cells that are crucial to normal craniofacial morphogenesis. PMID:23592613

Smith, Francis; Hu, Diane; Young, Nathan M; Lainoff, Alexis J; Jamniczky, Heather A; Maltepe, Emin; Hallgrimsson, Benedikt; Marcucio, Ralph S

2013-07-01

176

The effect of hypoxia on facial shape variation and disease phenotypes in chicken embryos  

PubMed Central

SUMMARY Craniofacial anomalies can arise from both genetic and environmental factors, including prenatal hypoxia. Recent clinical evidence correlates hypoxia to craniofacial malformations. However, the mechanisms by which hypoxia mediates these defects are not yet understood. We examined the cellular mechanisms underlying malformations induced by hypoxia using a chicken (Gallus gallus) embryo model. Eggs were incubated in either hypoxic (7, 9, 11, 13, 15, 17 or 19% O2) or normoxic (21% O2) conditions. Embryos were photographed for morphological analysis at days 3–6. For analysis of skeletal development, 13-day embryos were cleared and stained with alcian blue and alizarin red for cartilage and bone, respectively. Quantitative analysis of facial shape variation was performed on images of embryos via geometric morphometrics. Early-stage embryos (day 2) were analyzed for apoptosis via whole-mount and section TUNEL staining and immunostaining for cleaved caspase-3, whereas later-stage embryos (days 4–6) were sectioned in paraffin for analysis of cell proliferation (BrdU), apoptosis (TUNEL) and metabolic stress (phospho-AMPK). Results demonstrate that survival is reduced in a dose-dependent manner. Hypoxic embryos displayed a spectrum of craniofacial anomalies, from mild asymmetry and eye defects to more severe frontonasal and cephalic anomalies. Skull bone development was delayed in hypoxic embryos, with some skeletal defects observed. Morphometric analysis showed facial shape variation relative to centroid size and age in hypoxic groups. Hypoxia disrupted cell proliferation and, in early-stage embryos, caused apoptosis of neural crest progenitor cells. Hypoxic embryos also displayed an increased metabolic stress response. These results indicate that hypoxia during early embryonic craniofacial development might induce cellular oxidative stress, leading to apoptosis of the neural crest progenitor cells that are crucial to normal craniofacial morphogenesis.

Smith, Francis; Hu, Diane; Young, Nathan M.; Lainoff, Alexis J.; Jamniczky, Heather A.; Maltepe, Emin; Hallgrimsson, Benedikt; Marcucio, Ralph S.

2013-01-01

177

Drosophila americana as a Model Species for Comparative Studies on the Molecular Basis of Phenotypic Variation  

PubMed Central

Understanding the molecular basis of within and between species phenotypic variation is one of the main goals of Biology. In Drosophila, most of the work regarding this issue has been performed in D. melanogaster, but other distantly related species must also be studied to verify the generality of the findings obtained for this species. Here, we make the case for D. americana, a species of the virilis group of Drosophila that has been diverging from the model species, D. melanogaster, for approximately 40 Myr. To determine the suitability of this species for such studies, polymorphism and recombination estimates are presented for D. americana based on the largest nucleotide sequence polymorphism data set so far analyzed (more than 100 data sets) for this species. The polymorphism estimates are also compared with those obtained from the comparison of the genome assembly of two D. americana strains (H5 and W11) here reported. As an example of the general utility of these resources, we perform a preliminary study on the molecular basis of lifespan differences in D. americana. First, we show that there are lifespan differences between D. americana populations from different regions of the distribution range. Then, we perform five F2 association experiments using markers for 21 candidate genes previously identified in D. melanogaster. Significant associations are found between polymorphism at two genes (hep and Lim3) and lifespan. For the F2 association study involving the two sequenced strains (H5 and W11), we identify amino acid differences at Lim3 and Hep that could be responsible for the observed changes in lifespan. For both genes, no large gene expression differences were observed between the two strains.

Fonseca, Nuno A.; Morales-Hojas, Ramiro; Reis, Micael; Rocha, Helder; Vieira, Cristina P.; Nolte, Viola; Schlotterer, Christian; Vieira, Jorge

2013-01-01

178

Fluctuating environments and the role of mutation in maintaining quantitative genetic variation.  

PubMed

We study a class of genetic models in which a quantitative trait determined by several additive loci is subject to temporally fluctuating selection. Selection on the trait is assumed to be stabilizing but with an optimum that varies periodically and might be perturbed stochastically. The population mates at random, is infinitely large and has discrete generations. We pursue a statistical and numerical approach, covering a wide range of ecological and genetic parameters, to determine the potential of fluctuating environments to maintain quantitative genetic variation. Whereas, in contrast to some recent claims, this potential seems to be rather limited in the absence of recurrent mutation, fluctuating environments might, in combination with it, often generate high levels of additive genetic variation. We investigate how the genetic variation maintained depends on the ecological parameters and on the underlying genetics. PMID:12448856

Bürger, Reinhard; Gimelfarb, Alexander

2002-08-01

179

Phenotypic Consequences of Copy Number Variation: Insights from Smith-Magenis and Potocki-Lupski Syndrome Mouse Models  

PubMed Central

A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also “genome regulation.” Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype.

Chrast, Jacqueline; Gu, Wenli; Gheldof, Nele; Pradervand, Sylvain; Schutz, Frederic; Young, Juan I.; Lupski, James R.; Reymond, Alexandre; Walz, Katherina

2010-01-01

180

Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.  

PubMed

A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also "genome regulation." Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype. PMID:21124890

Ricard, Guénola; Molina, Jessica; Chrast, Jacqueline; Gu, Wenli; Gheldof, Nele; Pradervand, Sylvain; Schütz, Frédéric; Young, Juan I; Lupski, James R; Reymond, Alexandre; Walz, Katherina

2010-01-01

181

Detection of copy number variation and single nucleotide polymorphisms in genes involved in drug resistance and other phenotypic traits in P. falciparum clinical isolates collected from Uganda.  

PubMed

There is an increasing interest in mapping the genes of pathogens which underlie important phenotypic traits such as virulence and drug resistance. The Plasmodium falciparum genome exhibits sequence variation that contributes to the pathogenic mechanisms of the parasite. Determining the prevalence of resistance markers could provide a prediction about drug efficacy. Copy number polymorphism (CNP) of genes has been shown to influence important parasite phenotypes. In this work, CNPs within genes involved in drug resistance and other phenotypic traits namely P. falciparum multidrug resistance 1 (pfmdr-1), GTP cyclo hydrolase (gch1), Ring infected erythrocyte surface antigen precursor (resa) and a hypothetical protein coding gene were analyzed by quantitative real time-polymerase reaction (qRT-PCR) among clinical isolates collected from Uganda. The pfmdr-1 codons 86 and 1246 and P. falciparum chloroquine resistance (pfcrt) codon 76 were genotyped for single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the proportion of resistance associated mutations were determined among mild and severe malaria cases using the chi-square test. Forty and 42 P. falciparum isolates collected from children with mild and severe malaria respectively were analyzed for CNPs. Seventy five and 81 P. falciparum isolates from children with mild or severe malaria were analyzed for SNPs. No pfmdr-1, gch1 or novel gene amplifications were identified among the P. falciparum clinical isolates. Although chloroquine was officially withdrawn from policy use since 7 years, all P. falciparum isolates presented the associated pfcrt K76T mutation, whatever the clinical status and no specific mutation in the pfmdr-1 gene was associated with disease type. In conclusion, this study provides baseline measures for continued surveillance for changes in copy number and SNP types among genes implicated in drug resistance and other important phenotypes that may have a potential role in parasite virulence mechanisms or drug treatment outcomes. PMID:23220229

Kiwuwa, Mpungu Steven; Byarugaba, Justus; Wahlgren, Mats; Kironde, Fred

2013-03-01

182

[The effect of isogenization on the phenotypic manifestation of quantitative traits in Drosophila melanogaster].  

PubMed

A comparative analysis of the phenotypic values of the proximal and distal fragments of the radial wing vein was carried out in heterogeneous lines of Drosophila melanogaster and in isogenic lines derived from them with the help of a balancer line. The mean values of the traits in the isogenic lines were shown to significantly differ from the corresponding values in the "parental" heterogeneous lines. Apparently, the change in the trait values was caused by a double recombination exchange between the inverted and the "normal" chromosomes, which suggests partial crossing over suppression in the balancer lines. PMID:15523843

Vasil'eva, L A

2004-08-01

183

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

PubMed

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

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

2013-08-01

184

Founder effects and phenotypic variation in Adelges cooleyi , an insect pest introduced to the eastern United States  

Microsoft Academic Search

Introduced organisms experience founder effects including genetic bottlenecks that result in significant reductions in genetic\\u000a variation. Genetic bottlenecks may constrain the evolution of phenotypic traits that facilitate success in novel habitats.\\u000a We examined the effect of introduction into novel environments on genetic diversity of an insect pest, Adelges cooleyi, which was introduced into the eastern United States during the mid

Robert G. Ahern; David J. Hawthorne; Michael J. Raupp

2009-01-01

185

Phenotypic variation in sexually and asexually recruited individuals of the Baltic Sea endemic macroalga Fucus radicans: in the field and after growth in a common-garden  

PubMed Central

Background Most species of brown macroalgae recruit exclusively sexually. However, Fucus radicans, a dominant species in the northern Baltic Sea, recruits new attached thalli both sexually and asexually. The level of asexual recruitment varies among populations from complete sexual recruitment to almost (> 90%) monoclonal populations. If phenotypic traits have substantial inherited variation, low levels of sexual activity will decrease population variation in these traits, which may affect function and resilience of the species. We assessed the level of inherited variation in nine phenotypic traits by comparing variation within and among three monoclonal groups and one group of unique multilocus genotypes (MLGs) sampled in the wild. Results Of the nine phenotypic traits, recovery after freezing, recovery after desiccation, and phlorotannin content showed substantial inherited variation, that is, phenotypic variation in these traits were to a large extend genetically determined. In contrast, variation in six other phenotypic traits (growth rate, palatability to isopod grazers, thallus width, distance between dichotomies, water content after desiccation and photochemical yield under ambient conditions) did not show significant signals of genetic variation at the power of analyses used in the study. Averaged over all nine traits, phenotypic variation within monoclonal groups was only 68% of the variation within the group of different MLGs showing that genotype diversity does affect the overall level of phenotypic variation in this species. Conclusions Our result indicates that, in general, phenotypic diversity in populations of Fucus radicans increases with increased multilocus genotype (MLG) diversity, but effects are specific for individual traits. In the light of Fucus radicans being a foundation species of the northern Baltic Sea, we propose that increased MLG diversity (leading to increased trait variation) will promote ecosystem function and resilience in areas where F. radicans is common, but this suggestion needs experimental support.

2012-01-01

186

Sexual conflict and interacting phenotypes: a quantitative genetic analysis of fecundity and copula duration in Drosophila melanogaster.  

PubMed

Many reproductive traits that have evolved under sexual conflict may be influenced by both sexes. Investigation of the genetic architecture of such traits can yield important insight into their evolution, but this entails that the heritable component of variation is estimated for males and females-as an interacting phenotype. We address the lack of research in this area through an investigation of egg production and copula duration in the fruit fly, Drosophila melanogaster. Despite egg production rate being determined by both sexes, which may cause sexual conflict, an assessment of this trait as an interacting phenotype is lacking. It is currently unclear whether copula duration is determined by males and/or females. We found significant female, but not male, genetic variance for egg production rate that may indicate reduced potential for ongoing sexually antagonistic coevolution. In contrast, copula duration was determined by significant genetic variance in both sexes. We also identified genetic variation in egg retention among virgin females. Although previously identified in wild populations, it is unclear why this should be present in a laboratory stock. This study provides a novel insight into the shared genetic architecture of reproductive traits that are the subject of sexual conflict. PMID:24495114

Edward, Dominic A; Poissant, Jocelyn; Wilson, Alastair J; Chapman, Tracey

2014-06-01

187

Phenotypes, genotypes and disease susceptibility associated with gene copy number variations: complement C4 CNVs in European American healthy subjects and those with systemic lupus erythematosus  

PubMed Central

A new paradigm in human genetics is high frequencies of inter-individual variations in copy numbers of specific genomic DNA segments. Such common copy number variation (CNV) loci often contain genes engaged in host-environment interaction including those involved in immune effector functions. DNA sequences within a CNV locus often share a high degree of identity but beneficial or deleterious polymorphic variants are present among different individuals. Thus, common gene CNVs can contribute, both qualitatively and quantitatively, to a spectrum of phenotypic variants. In this review we describe the phenotypic and genotypic diversities of complement C4 created by copy number variations of RCCX modules (RP-C4-CYP21-TNX) and size dichotomy of C4 genes. A direct outcome of C4 CNV is the generation of two classes of polymorphic proteins, C4A and C4B, with differential chemical reactivities towards peptide or carbohydrate antigens, and a range of C4 plasma protein concentrations (from 15 to 70 mg/dl) among healthy subjects. Deliberate molecular genetic studies enabled development of definitive techniques to determine exact patterns of RCCX modular variations, copy numbers of long and short C4A and C4B genes by Southern blot analyses or by real-time quantitative PCR. It is found that in healthy European Americans, the total C4 gene copy number per diploid genome ranges from 2 to 6: 60.8% of people with four copies of C4 genes, 27.2% with less than four copies, and 12% with more than four copies. Such a distribution is skewed towards the low copy number side in patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disease with complex etiology. In SLE, the frequency of individuals with less than four copies of C4 is significantly increased (42.2%), while the frequency of those with more than four copies is decreased (6%). This decrease in total C4 gene copy number in SLE is due to increases in homozygous and heterozygous deficiencies of C4A but not C4B. Therefore, it is concluded that lower copy number of C4 is a risk factor for and higher gene copy number of C4 is a protective factor against SLE disease susceptibility.

Wu, Y.L.; Yang, Y.; Chung, E.K.; Zhou, B.; Kitzmiller, K.J.; Savelli, S.L.; Nagaraja, H.N.; Birmingham, D.J.; Tsao, B.P.; Rovin, B.H.; Hebert, L.A.; Yu, C.Y.

2009-01-01

188

Quantitative Genetic Variation of Odor-Guided Behavior in a Natural Population of Drosophila Melanogaster  

PubMed Central

Quantitative genetic variation in behavioral response to the odorant, benzaldehyde, was assessed among a sample of 43 X and 35 third chromosomes extracted from a natural population and substituted into a common inbred background. Significant genetic variation among chromosome lines was detected. Heritability estimates for olfactory response, however, were low, as is typical for traits under natural selection. Furthermore, the loci affecting naturally occurring variation in olfactory response to benzaldehyde were not the same in males and females, since the genetic correlation between the sexes was low and not significantly different from zero for the chromosome 3 lines. Competitive fitness, viability and fertility of the chromosome 3 lines were estimated using the balancer equilibrium technique. Genetic correlations between fitness and odor-guided behavior were not significantly different from zero, suggesting the number of loci causing variation in olfactory response is small relative to the number of loci causing variation in fitness. Since different genes affect variation in olfactory response in males and females, genetic variation for olfactory response could be maintained by genotype X sex environment interaction. This unusual genetic architecture implies that divergent evolutionary trajectories for olfactory behavior may occur in males and females.

Mackay, TFC.; Hackett, J. B.; Lyman, R. F.; Wayne, M. L.; Anholt, RRH.

1996-01-01

189

Quantitative genetic variation of odor-guided behavior in a natural population of Drosophila melanogaster.  

PubMed

Quantitative genetic variation in behavioral response to the odorant, benzaldehyde, was assessed among a sample of 43 X and 35 third chromosomes extracted from a natural population and substituted into a common inbred background. Significant genetic variation among chromosome lines was detected. Heritability estimates for olfactory response, however, were low, as is typical for traits under natural selection. Furthermore, the loci affecting naturally occurring variation in olfactory response to benzaldehyde were not the same in males and females, since the genetic correlation between the sexes was low and not significantly different from zero for the chromosome 3 lines. Competitive fitness, viability and fertility of the chromosome 3 lines were estimated using the balancer equilibrium technique. Genetic correlations between fitness and odor-guided behavior were not significantly different from zero, suggesting the number of loci causing variation in olfactory response is small relative to the number of loci causing variation in fitness. Since different genes affect variation in olfactory response in males and females, genetic variation for olfactory response could be maintained by genotype x sex environment interaction. This unusual genetic architecture implies that divergent evolutionary trajectories for olfactory behavior may occur in males and females. PMID:8889533

Mackay, T F; Hackett, J B; Lyman, R F; Wayne, M L; Anholt, R R

1996-10-01

190

Factors other than genotype account largely for the phenotypic variation of the pulmonary valve in Syrian hamsters  

PubMed Central

Understanding of the aetiology of congenitally anomalous pulmonary valves remains incomplete. The aim of our study, therefore, was to elucidate the degree to which the phenotypic variation known to exist for the pulmonary valve relies on genotypic variation. Initially, we tested the hypothesis that genetically alike individuals would display similar valvar phenotypes if the phenotypic arrangement depended entirely, or almost entirely, on the genotype. Thus, we examined pulmonary valves from 982 Syrian hamsters belonging to two families subject to systematic inbreeding by crossing siblings. Their coefficient of inbreeding was 0.999 or higher, so they could be considered genetically alike. External environmental factors were standardized as much as possible. A further 97 Syrian hamsters from an outbred colony were used for comparative purposes. In both the inbred and outbred hamsters, we found valves with a purely trifoliate, or tricuspid, design, trifoliate valves with a more or less extensive fusion of the right and left leaflets, bifoliate, or bicuspid, valves with fused right and left leaflets, with or without a raphe located in the conjoined arterial sinus, and quadrifoliate, or quadricuspid, valves. The incidence of the different valvar morphological variants was similar in the outbred and inbred colonies, except for the bifoliate pulmonary valves, which were significantly more frequent in the hamsters from one of the two inbred families. Results of crosses between genetically alike hamsters revealed no significant association between the pulmonary valvar phenotypes as seen in the parents and their offspring. The incidence of bifoliate pulmonary valves, nonetheless, was higher than statistically expected in the offspring of crosses where at least one of the parents possessed a pulmonary valve with two leaflets. Our observations are consistent with the notion that the basic design of the pulmonary valve, in terms of whether it possesses three or two leaflets, relies on genotypic determinants. They also denote that the bifoliate condition of the valve is the consequence of complex inheritance, with reduced penetrance and variable expressivity. Moreover, in showing that the incidence of the bifoliate pulmonary valve significantly differs in two different isogenetic backgrounds, our data suggest that genetic modifiers might be implicated in directing the manifestation of such specific pulmonary valvar malformations. Finally, our findings indicate that factors other than the genotype, operating during embryonic life and creating developmental noise, or random variation, play a crucial role in the overall phenotypic variation involving the pulmonary valve.

Carmen Fernandez, M; Duran, Ana C; Fernandez, Borja; Arque, Josep M; Anderson, Robert H; Sans-Coma, Valentin

2012-01-01

191

Phenotypic Variation across Chromosomal Hybrid Zones of the Common Shrew (Sorex araneus) Indicates Reduced Gene Flow  

PubMed Central

Sorex araneus, the Common shrew, is a species with more than 70 karyotypic races, many of which form parapatric hybrid zones, making it a model for studying chromosomal speciation. Hybrids between races have reduced fitness, but microsatellite markers have demonstrated considerable gene flow between them, calling into question whether the chromosomal barriers actually do contribute to genetic divergence. We studied phenotypic clines across two hybrid zones with especially complex heterozygotes. Hybrids between the Novosibirsk and Tomsk races produce chains of nine and three chromosomes at meiosis, and hybrids between the Moscow and Seliger races produce chains of eleven. Our goal was to determine whether phenotypes show evidence of reduced gene flow at hybrid zones. We used maximum likelihood to fit tanh cline models to geometric shape data and found that phenotypic clines in skulls and mandibles across these zones had similar centers and widths as chromosomal clines. The amount of phenotypic differentiation across the zones is greater than expected if it were dissipating due to unrestricted gene flow given the amount of time since contact, but it is less than expected to have accumulated from drift during allopatric separation in glacial refugia. Only if heritability is very low, Ne very high, and the time spent in allopatry very short, will the differences we observe be large enough to match the expectation of drift. Our results therefore suggest that phenotypic differentiation has been lost through gene flow since post-glacial secondary contact, but not as quickly as would be expected if there was free gene flow across the hybrid zones. The chromosomal tension zones are confirmed to be partial barriers that prevent differentiated races from becoming phenotypically homogenous.

Polly, P. David; Polyakov, Andrei V.; Ilyashenko, Vadim B.; Onischenko, Sergei S.; White, Thomas A.; Shchipanov, Nikolay A.; Bulatova, Nina S.; Pavlova, Svetlana V.; Borodin, Pavel M.; Searle, Jeremy B.

2013-01-01

192

Conformation of polyelectrolytes in poor solvents: variational approach and quantitative comparison with scaling predictions.  

PubMed

We present the results of variational calculations of a polyelectrolyte solution with low salt in poor solvent conditions for a polymer backbone. By employing the variation method, we quantitatively determined the diagram of the state of the polyelectrolyte in poor solvents as a function of the charge density and the molecular weight. The exact structure and diagram of the polyelectrolyte were compared to the scaling predictions of the necklace model developed by Dobrynin and Rubinstein [Prog. Polym. Sci. 30, 1049-1118 (2005); Dobrynin and Rubinstein, Macromolecules 32, 915-922 (1999); Dobrynin and Rubinstein, Macromolecules 34, 1964-1972 (2001)]. We find that the scaling necklace model may be used as a rather good estimation and analytical approximation of the exact variational model. It is also pointed out that the molecular connection of polymer is crucial for ellipsoid and necklace conformation. PMID:24852561

Tang, Haozhe; Liao, Qi; Zhang, Pingwen

2014-05-21

193

Conformation of polyelectrolytes in poor solvents: Variational approach and quantitative comparison with scaling predictions  

NASA Astrophysics Data System (ADS)

We present the results of variational calculations of a polyelectrolyte solution with low salt in poor solvent conditions for a polymer backbone. By employing the variation method, we quantitatively determined the diagram of the state of the polyelectrolyte in poor solvents as a function of the charge density and the molecular weight. The exact structure and diagram of the polyelectrolyte were compared to the scaling predictions of the necklace model developed by Dobrynin and Rubinstein [Prog. Polym. Sci. 30, 1049-1118 (2005); Dobrynin and Rubinstein, Macromolecules 32, 915-922 (1999); Dobrynin and Rubinstein, Macromolecules 34, 1964-1972 (2001)]. We find that the scaling necklace model may be used as a rather good estimation and analytical approximation of the exact variational model. It is also pointed out that the molecular connection of polymer is crucial for ellipsoid and necklace conformation.

Tang, Haozhe; Liao, Qi; Zhang, Pingwen

2014-05-01

194

Identification of Quantitative Trait Loci Underlying Proteome Variation in Human Lymphoblastoid Cells*  

PubMed Central

Population-based variability in protein expression patterns, especially in humans, is often observed but poorly understood. Moreover, very little is known about how interindividual genetic variation contributes to protein expression patterns. To begin to address this, we describe elements of technical and biological variations contributing to expression of 544 proteins in a population of 24 individual human lymphoblastoid cell lines that have been extensively genotyped as part of the International HapMap Project. We determined that expression levels of 10% of the proteins were tightly correlated to cell doubling rates. Using the publicly available genotypes for these lymphoblastoid cell lines, we applied a genetic association approach to identify quantitative trait loci associated with protein expression variation. Results identified 24 protein forms corresponding to 15 proteins for which genetic elements were responsible for >50% of the expression variation. The genetic variation associated with protein expression levels were located in cis with the gene coding for the transcript of the protein for 19 of these protein forms. Four of the genetic elements identified were coding non-synonymous single nucleotide polymorphisms that resulted in migration pattern changes in the two-dimensional gel. This is the first description of large scale proteomics analysis demonstrating the direct relationship between genome and proteome variations in human cells.

Garge, Nikhil; Pan, Huaqin; Rowland, Megan D.; Cargile, Benjamin J.; Zhang, Xinxin; Cooley, Phillip C.; Page, Grier P.; Bunger, Maureen K.

2010-01-01

195

Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan.  

PubMed

A nationwide survey was conducted for identifying ataxia-telangiectasia (AT) patients in Japan. Eighty-nine patients were diagnosed between 1971 and 2006. Detailed clinical and laboratory data of 64 patients including affected siblings were collected. Analyses focused on malignancy, therapy-related toxicity, infection, and hematological/immunological parameters. The phenotypic variability of AT was assessed by comparing 26 affected siblings from 13 families. Malignancy developed in 22% of the cases and was associated with a high rate of severe therapy-related complications: chemotherapy-related cardiac toxicity in 2 children, and severe hemorrhagic cystitis requiring surgery in 2 patients. The frequency of serious viral infections correlated with the T cell count. Hypogammaglobulinemia with hyper-IgM (HIGM) was recorded in 5 patients, and 3 patients developed panhypogammaglobulinemia. Differences in immunological parameters were noted in siblings. Four patients showed an HIGM phenotype, in contrast to their siblings with normal IgG and IgM levels. The patients with HIGM phenotype showed reduced levels of TRECs and CD27+CD20+ memory B cells. The findings suggest that hitherto unidentified modifier genes or exogenous environmental factors can influence the overall immune responses. Our data along with future prospective study will lead to better understanding of the hematological/immunological phenotypes and to better care of the patients. PMID:19705055

Morio, Tomohiro; Takahashi, Naomi; Watanabe, Fumiaki; Honda, Fumiko; Sato, Masaki; Takagi, Masatoshi; Imadome, Ken-ichi; Miyawaki, Toshio; Delia, Domenico; Nakamura, Kotoka; Gatti, Richard A; Mizutani, Shuki

2009-11-01

196

Temporal environmental variation and phenotypic plasticity: a mechanism underlying priority effects  

Microsoft Academic Search

Understanding the role of history in the formation of communities has been a major challenge in community ecology. Here, we explore the role of phenotypic plasticity and its associated trait-mediated indirect interactions as a mechanism behind priority effects. Using organisms with inducible defenses as a model system, we examine how aquatic communities initially containing different predator environments are affected at

Jason T. Hoverman; Rick A. Relyea

2008-01-01

197

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

PubMed

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

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

2012-01-01

198

Fleece variation in alpaca (Vicugna pacos): a two-locus model for the Suri/Huacaya phenotype  

PubMed Central

Background Genetic improvement of fibre-producing animal species has often induced transition from double coated to single coated fleece, accompanied by dramatic changes in skin follicles and hair composition, likely implying variation at multiple loci. Huacaya, the more common fleece phenotype in alpaca (Vicugna pacos), is characterized by a thick dense coat growing perpendicularly from the body, whereas the alternative rare and more prized single-coated Suri phenotype is distinguished by long silky fibre that grows parallel to the body and hangs in separate, distinctive pencil locks. A single-locus genetic model has been proposed for the Suri-Huacaya phenotype, where Huacaya is recessive. Results Two reciprocal experimental test-crosses (Suri × Huacaya) were carried out, involving a total of 17 unrelated males and 149 unrelated females. An additional dataset of 587 offspring of Suri × Suri crosses was analyzed. Segregation ratios, population genotype frequencies, and/or recombination fraction under different genetic models were estimated by maximum likelihood. The single locus model for the Suri/Huacaya phenotype was rejected. In addition, we present two unexpected observations: 1) a large proportion (about 3/4) of the Suri animals are segregating (with at least one Huacaya offspring), even in breeding conditions where the Huacaya trait would have been almost eliminated; 2) a model with two different values of the segregation ratio fit the data significantly better than a model with a single parameter. Conclusions The data support a genetic model in which two linked loci must simultaneously be homozygous for recessive alleles in order to produce the Huacaya phenotype. The estimated recombination rate between these loci was 0.099 (95% C.L. = 0.029-0.204). Our genetic analysis may be useful for other species whose breeding system produces mainly half-sib families.

2010-01-01

199

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

PubMed Central

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.

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

2011-01-01

200

DLX3 mutation in a new family and its phenotypic variations.  

PubMed

Tricho-dento-osseous syndrome (TDO) is an autosomal-dominant disease characterized by curly hair at birth, enamel hypoplasia, taurodontism, and a thick cortical bone. A common DLX3 gene mutation (c.571_574delGGGG) has been identified in multiple families with variable clinical phenotypes. Recently, another DLX3 gene mutation (c.561_562delCT) was reported to cause amelogenesis imperfecta with taurodontism (AIHHT). We identified a Korean family with overlapping phenotypes of TDO and AIHHT. We performed mutational analysis to discover its genetic etiology. The identified mutation was c.561_562delCT mutation in the DLX3 gene. The enamel was hypomature and hypoplastic. The characteristic taurodontic features were not identified. Increased bone density or thickness could not be revealed by cephalometric, hand-wrist, and panoramic radiographs. Affected individuals reported that their nails were brittle, and they had curly hair at birth. This study clearly showed that the c.561_562delCT mutation had not only enamel defects, but also other clinical phenotypes resembling those of TDO syndrome. PMID:18362318

Lee, S-K; Lee, Z H; Lee, S-J; Ahn, B-D; Kim, Y-J; Lee, S-H; Kim, J-W

2008-04-01

201

Metabolite profiling and quantitative genetics of natural variation for flavonoids in Arabidopsis.  

PubMed

Little is known about the range and the genetic bases of naturally occurring variation for flavonoids. Using Arabidopsis thaliana seed as a model, the flavonoid content of 41 accessions and two recombinant inbred line (RIL) sets derived from divergent accessions (Cvi-0×Col-0 and Bay-0×Shahdara) were analysed. These accessions and RILs showed mainly quantitative rather than qualitative changes. To dissect the genetic architecture underlying these differences, a quantitative trait locus (QTL) analysis was performed on the two segregating populations. Twenty-two flavonoid QTLs were detected that accounted for 11-64% of the observed trait variations, only one QTL being common to both RIL sets. Sixteen of these QTLs were confirmed and coarsely mapped using heterogeneous inbred families (HIFs). Three genes, namely TRANSPARENT TESTA (TT)7, TT15, and MYB12, were proposed to underlie their variations since the corresponding mutants and QTLs displayed similar specific flavonoid changes. Interestingly, most loci did not co-localize with any gene known to be involved in flavonoid metabolism. This latter result shows that novel functions have yet to be characterized and paves the way for their isolation. PMID:22442426

Routaboul, Jean-Marc; Dubos, Christian; Beck, Gilles; Marquis, Catherine; Bidzinski, Przemyslaw; Loudet, Olivier; Lepiniec, Loïc

2012-06-01

202

Contrasting the distribution of phenotypic and molecular variation in the freshwater snail Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni  

PubMed Central

Population differentiation was investigated by confronting phenotypic and molecular variation in the highly selfing freshwater snail Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni. We sampled seven natural populations separated by a few kilometers, and characterized by different habitat regimes (permanent/temporary) and openness (open/closed). A genetic analysis based on five microsatellite markers confirms that B. pfeifferi is a selfer (s?0.9) and exhibits limited variation within populations. Most pairwise FST were significant indicating marked population structure, though no isolation by distance was detected. Families from the seven populations were monitored under laboratory conditions over two generations (G1 and G2), allowing to record several life-history traits, including growth, fecundity and survival, over 25 weeks. Marked differences were detected among populations for traits expressed early in the life cycle (up to sexual maturity). Age and size at first reproduction had high heritability values, but such a trend was not found for early reproductive traits. In most populations, G1 snails matured later and at a larger size than G2 individuals. Individuals from permanent habitats matured at a smaller size and were more fecund than those from temporary habitats. The mean phenotypic differentiation over all populations (QST) was lower than the mean genetic differentiation (FST), suggesting stabilizing selection. However, no difference was detected between QST and FST for both habitat regime and habitat openness.

Tian-Bi, Y-NT; Jarne, P; Konan, J-NK; Utzinger, J; N'Goran, E K

2013-01-01

203

Phenotypic evolution and hidden speciation in Candidula unifasciata ssp. (Helicellinae, Gastropoda) inf erred by 16s variathn and quantitative shell traits  

Microsoft Academic Search

In an effort to link quantitative morphometric information with molecular data on the popu- lation level, we have analysed 19 populations of the conchologically variable land snail Candidula unifasciata from across the species range for variation in quantitative shell traits L and at the mitochondrial16S ribosomai (r)DNA locus. In genetic analysis, including 21 additional populations, we observed two fundamental haplotype

MARKUS PFENNINGER; Bio-Campus Siesmayerstra

204

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

PubMed Central

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.

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

205

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

PubMed Central

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.

Perez-Ortega, Sergio; Fernandez-Mendoza, Fernando; Raggio, Jose; Vivas, Mercedes; Ascaso, Carmen; Sancho, Leopoldo G.; Printzen, Christian; de los Rios, Asuncion

2012-01-01

206

Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7.  

PubMed Central

Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and approximately 73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is approximately 15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans.

Duggirala, R.; Stern, M. P.; Mitchell, B. D.; Reinhart, L. J.; Shipman, P. A.; Uresandi, O. C.; Chung, W. K.; Leibel, R. L.; Hales, C. N.; O'Connell, P.; Blangero, J.

1996-01-01

207

Snail phenotypic variation and stress proteins: do different heat response strategies contribute to Waddington's widget in field populations?  

PubMed

On the basis of studies with laboratory strains of Drosophila and Arabidopsis, it has been hypothesized that potential buffers to the expression of phenotypic morphological variation, such as Hsp90 and possibly Hsp70, represent important components of Waddington's widget, which may confer capacitive evolution. As studies on field populations of living organisms to test this hypothesis are lacking, we tested whether a heat response strategy involving high stress protein levels is associated with low morphological variation and vice versa, using four natural populations of Mediterranean pulmonate snails. In response to 8 hr of elevated temperatures, a population of Xeropicta derbentina with uniform shell pigmentation pattern showed remarkably high Hsp70 but low Hsp90 levels. In contrast, a highly variable population of Cernuella virgata kept both Hsp90 and Hsp70 levels low when held at diverse though environmentally relevant temperatures. Two other populations (Theba pisana and another X. derbentina population) with intermediate variation in shell pigmentation pattern were also intermediate in inducing Hsp70, though Hsp90 was maintained at a low level. The observed correlation of stress protein levels and coloration pattern variation provide the first indirect evidence for an association of stress proteins with Waddington's widget under natural conditions. PMID:19065565

Köhler, Heinz-R; Lazzara, Raimondo; Dittbrenner, Nils; Capowiez, Yvan; Mazzia, Christophe; Triebskorn, Rita

2009-03-15

208

Patterns of genetic and phenotypic variation in Iris haynei and I. atrofusca (Iris sect. Oncocyclus = the royal irises) along an ecogeographical gradient in Israel and the West Bank  

Microsoft Academic Search

Iris haynei and I. atrofusca are two closely related narrow endemics distributed vicariously along an ecogeographical north - south gradient in Israel and the West Bank. To obtain baseline information of the taxonomic status, conservation and population history of these taxa, we investigated patterns of phenotypic variation and the partitioning of genetic variation within and among populations using dominant random

R. M. H Arafeh; Y Sapir; A Shmida; N Iraki; O Fragman; H. P Comes

2002-01-01

209

Quantitative genetic variation in the control of ovarian apoptosis under different environments.  

PubMed

Fertility loss in otherwise healthy individuals can be an evolutionary conundrum. Most studies on the evolution of post-reproductive lifespan focus on the fitness effects of survival past the age of last reproduction. A complementary approach, which has been largely neglected, is to develop an understanding of the nature of variation in the mechanism underlying loss of fertility, ovarian apoptosis. Variation in the genetics underlying the regulation of ovarian apoptosis could hold the key to understanding the evolution of midlife fertility loss. We estimated quantitative genetic variation in the regulation of ovarian apoptosis in females of the cockroach Nauphoeta cinerea, an insect with reproductive cycles. We have earlier shown that delaying reproduction incites loss of fertility. Here, we forced females to delay reproduction under conditions of excess or limited food and examined apoptosis under both conditions. We found substantial additive genetic variation in levels of apoptosis when females experienced a limited period of starvation during sexual maturation but not when females had unlimited access to food. Hence, selection could act on the regulation of ovarian apoptosis to change the rate of fertility loss with age at least under some environmental circumstances. Our results suggest that an understanding of how loss of fertility evolves requires an understanding of the interaction between genes involved in the regulation of apoptosis and environmental factors such as diet. PMID:19401711

Edvardsson, M; Hunt, J; Moore, A J; Moore, P J

2009-09-01

210

Transforming growth factor-beta2 is involved in quantitative genetic variation in thymic involution.  

PubMed

The mechanisms regulating thymic involution are unclear. In inbred mouse strains the rate of thymic involution and the function of the hematopoietic stem cell (HSC) compartment are subject to quantitative genetic variation. We have shown previously that transforming growth factor-beta2 (TGF-beta2) is a genetically determined positive regulator of HSCs. Here, we demonstrate that genetic variation in the rate of thymic involution correlates with genetic variation in the responsiveness of hematopoietic stem and progenitor cells to TGF-beta2. Corroborating these correlations, thymic cellularity and peripheral naive T-cell frequency were higher in old Tgfb2+/- mice than in wild-type littermates. The frequency of early T-cell precursors was increased in Tgfb2+/- mice, suggesting that TGF-beta2 affects the earliest stages of T-cell development in old mice. Reciprocal transplantation experiments indicated that TGF-beta2 expressed both in the (micro)environment and in the hematopoietic system can accelerate thymic involution; however, the age of the stem cells appeared irrelevant. Thus, although thymic involution is largely determined by the aged environment, TGF-beta2 plays a major modulatory role that is subject to genetic variation and is possibly mediated through its regulatory effects on early hematopoiesis. PMID:16282338

Kumar, Ritu; Langer, Jessica C; Snoeck, Hans-Willem

2006-03-01

211

Somaclonal variation in Coffea arabica: effects of genotype and embryogenic cell suspension age on frequency and phenotype of variants.  

PubMed

We determined how age of embryogenic cell suspensions affects somaclonal variation in five F1 hybrids of Coffea arabica L. Batches of plants were produced either directly from embryogenic callus, or after 3, 6, 9 and 12 months of embryogenic cell suspension culture. Seven phenotypic variants were characterized. Based on vigor and productivity of the regenerated plants, we classified the variants in order of increasing severity of physiological disorders as: Juvenile leaf color, Giant, Dwarf, Thick leaf (Bullata), Variegata, Angustifolia, and Multi-stem. The Dwarf, Angustifolia and Multi-stem variants were the most frequent among the regenerated plants (1.4, 4.8 and 2.9%, respectively). The frequency (f) of variants increased exponentially with the age (t) of the embryogenic suspension, in accordance with the function f = 0.99e(0.267t). For all genotypes, somaclonal variation was low (1.3%) in plants produced from embryogenic callus or 3-month-old cell suspensions and increased in frequency with increasing suspension age (6, 10 and 25% in plants produced from cell suspensions aged 6, 9 and 12 months, respectively). Large differences in somaclonal variation among genotypes were found only in plants produced from 12-month-old cell suspensions. For two genotypes, the oldest suspensions produced a majority of somaclonal variants (80-90%), whereas somaclonal variation ranged between 8 and 18% in the other genotypes. Cell suspension age and genotype also affected the type of variant produced. The severity of somaclonal variations increased with cell suspension age. For all genotypes combined, the Angustifolia variant was the most common. The other somaclonal variations were specific to certain genotypes or distributed randomly among the genotypes. PMID:12642244

Etienne, H; Bertrand, B

2003-04-01

212

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

PubMed Central

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.

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

2013-01-01

213

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

PubMed

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

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

2013-11-01

214

Quantitative genetics of floral traits in a gynodioecious wild strawberry Fragaria virginiana: implications for the independent evolution of female and hermaphrodite floral phenotypes  

Microsoft Academic Search

The independent evolution of floral phenotype is an important part of the process of gender specialization during the evolution of dioecy from hermaphroditism. However, we have little information on the genetic variation of floral traits in species with separate genders. Gynodioecious species (co-occurrence of females and hermaphrodites) have a breeding system intermediate between hermaphroditism and complete separation of the sexes

Tia Lynn Ashman

1999-01-01

215

Genetic variation and phenotypic plasticity in a trophically polymorphic population of pumpkinseed sunfish ( Lepomis gibbosus )  

Microsoft Academic Search

Summary Adaptive variation can exist at a variety of scales in biological systems, including among species, among local populations of a single species and among individuals within a single population. Trophic or resource polymorphisms in fishes are a good example of the lowest level of this hierarchy. In lakes without bluegill sunfish (Lepomis macrochirus), pumpkinseed sunfish (Lepomis gibbosus) can be

Beren W. Robinson; David Sloan Wilson

1996-01-01

216

Colour and size variation in Junonia villida (Lepidoptera, Nymphalidae): subspecies or phenotypic plasticity?  

Microsoft Academic Search

Colour pattern and size variation in the widespread Indo-Pacific Meadow Argus butterfly, Junonia villida (Fabricius, 1787), are reviewed based largely on examination of c. 1500 museum specimens from across its entire geographical range. Including villida, 14 available species-group names for this taxon are documented. The butterfly is recorded from some 200 islands or island groups. Larvae are reported to feed

R. I. VANE-WRIGHT; W. JOHN TENNENT

2011-01-01

217

Genome-wide association mapping identifies the genetic basis of discrete and quantitative variation in sexual weaponry in a wild sheep population.  

PubMed

Understanding the genetic architecture of phenotypic variation in natural populations is a fundamental goal of evolutionary genetics. Wild Soay sheep (Ovis aries) have an inherited polymorphism for horn morphology in both sexes, controlled by a single autosomal locus, Horns. The majority of males have large normal horns, but a small number have vestigial, deformed horns, known as scurs; females have either normal horns, scurs or no horns (polled). Given that scurred males and polled females have reduced fitness within each sex, it is counterintuitive that the polymorphism persists within the population. Therefore, identifying the genetic basis of horn type will provide a vital foundation for understanding why the different morphs are maintained in the face of natural selection. We conducted a genome-wide association study using ?36000 single nucleotide polymorphisms (SNPs) and determined the main candidate for Horns as RXFP2, an autosomal gene with a known involvement in determining primary sex characters in humans and mice. Evidence from additional SNPs in and around RXFP2 supports a new model of horn-type inheritance in Soay sheep, and for the first time, sheep with the same horn phenotype but different underlying genotypes can be identified. In addition, RXFP2 was shown to be an additive quantitative trait locus (QTL) for horn size in normal-horned males, accounting for up to 76% of additive genetic variation in this trait. This finding contrasts markedly from genome-wide association studies of quantitative traits in humans and some model species, where it is often observed that mapped loci only explain a modest proportion of the overall genetic variation. PMID:21651634

Johnston, Susan E; McEwan, John C; Pickering, Natalie K; Kijas, James W; Beraldi, Dario; Pilkington, Jill G; Pemberton, Josephine M; Slate, Jon

2011-06-01

218

Variation in antibiotic-induced microbial recolonization impacts on the host metabolic phenotypes of rats.  

PubMed

The interaction between the gut microbiota and their mammalian host is known to have far-reaching consequences with respect to metabolism and health. We investigated the effects of eight days of oral antibiotic exposure (penicillin and streptomycin sulfate) on gut microbial composition and host metabolic phenotype in male Han-Wistar rats (n = 6) compared to matched controls. Early recolonization was assessed in a third group exposed to antibiotics for four days followed by four days recovery (n = 6). Fluorescence in situ hybridization analysis of the intestinal contents collected at eight days showed a significant reduction in all bacterial groups measured (control, 10(10.7) cells/g feces; antibiotic-treated, 10(8.4)). Bacterial suppression reduced the excretion of mammalian-microbial urinary cometabolites including hippurate, phenylpropionic acid, phenylacetylglycine and indoxyl-sulfate whereas taurine, glycine, citrate, 2-oxoglutarate, and fumarate excretion was elevated. While total bacterial counts remained notably lower in the recolonized animals (10(9.1) cells/g faeces) compared to the controls, two cage-dependent subgroups emerged with Lactobacillus/Enterococcus probe counts dominant in one subgroup. This dichotomous profile manifested in the metabolic phenotypes with subgroup differences in tricarboxylic acid cycle metabolites and indoxyl-sulfate excretion. Fecal short chain fatty acids were diminished in all treated animals. Antibiotic treatment induced a profound effect on the microbiome structure, which was reflected in the metabotype. Moreover, the recolonization process was sensitive to the microenvironment, which may impact on understanding downstream consequences of antibiotic consumption in human populations. PMID:21591676

Swann, Jonathan R; Tuohy, Kieran M; Lindfors, Peter; Brown, Duncan T; Gibson, Glenn R; Wilson, Ian D; Sidaway, James; Nicholson, Jeremy K; Holmes, Elaine

2011-08-01

219

Quantitative variation of the common acute lymphoblastic leukemia antigen (gp100) on leukemic marrow blasts.  

PubMed Central

Marrow blasts from children with B cell precursor acute lymphoblastic leukemia (ALL) were studied for differences in quantitative expression of the common ALL antigen (CALLA). Of 42 untreated patients, 35 had detectable amounts of CALLA by flow cytometric (FCM) analysis of J-5 monoclonal antibody binding. Using an FCM technique that provides correlated measurements of a given cell surface antigen, cell size, and DNA content, we detected increased CALLA expression as lymphoblasts moved from G0/G1 phase through S phase of the cell cycle. The density of the antigen (per unit of blast surface area) remained relatively constant over the same interval, indicating that the change was not due to S phase-specific enhancement of CALLA expression. Eight cases had hyperdiploid cellular DNA content and in seven of these, only cells with clonal abnormalities of DNA content expressed the CALLA marker. Mean amounts of CALLA for each patient ranged widely within the study group, from very high to marginally detectable. This variation had no discernible relation to cell size, stem-line DNA content, percentage of cells in S phase, or the presence or absence of cytoplasmic immunoglobulin. Results of a univariate proportional hazards analysis showed that both quantitative level of CALLA for S phase cells (P = 0.048) and white blood cell count (P = 0.012) had made significant contributions to treatment outcome. Patients with relative amounts of CALLA less than the median value for the entire CALLA+ group had a higher rate of failure, which was virtually identical to that for the seven HLA-DR+ patients whose blasts lacked detectable CALLA. The observed interpatient variation in quantitative expression of CALLA is consistent with recognized steps in B cell precursor differentiation and may be useful in distinguishing patients with a less favorable prognosis. Images

Look, A T; Melvin, S L; Brown, L K; Dockter, M E; Roberson, P K; Murphy, S B

1984-01-01

220

From micro- to macroevolution through quantitative genetic variation: positive evidence from field crickets.  

PubMed

Quantitative genetics has been introduced to evolutionary biologists with the suggestion that microevolution could be directly linked to macroevolutionary patterns using, among other parameters, the additive genetic variance/ covariance matrix (G) which is a statistical representation of genetic constraints to evolution. However, little is known concerning the rate and pattern of evolution of G in nature, and it is uncertain whether the constraining effect of G is important over evolutionary time scales. To address these issues, seven species of field crickets from the genera Gryllus and Teleogryllus were reared in the laboratory, and quantitative genetic parameters for morphological traits were estimated from each of them using a nested full-sibling family design. We used three statistical approaches (T method, Flury hierarchy, and Mantel test) to compare G matrices or genetic correlation matrices in a phylogenetic framework. Results showed that G matrices were generally similar across species, with occasional differences between some species. We suggest that G has evolved at a low rate, a conclusion strengthened by the consideration that part of the observed across-species variation in G can be explained by the effect of a genotype by environment interaction. The observed pattern of G matrix variation between species could not be predicted by either morphological trait values or phylogeny. The constraint hypothesis was tested by comparing the multivariate orientation of the reconstructed ancestral G matrix to the orientation of the across-species divergence matrix (D matrix, based on mean trait values). The D matrix mainly revealed divergence in size and, to a much smaller extent, in a shape component related to the ovipositor length. This pattern of species divergence was found to be predictable from the ancestral G matrix in agreement with the expectation of the constraint hypothesis. Overall, these results suggest that the G matrix seems to have an influence on species divergence, and that macroevolution can be predicted, at least qualitatively, from quantitative genetic theory. Alternative explanations are discussed. PMID:15562691

Bégin, Mattieu; Roff, Derek A

2004-10-01

221

Rapid Visualisation of Microarray Copy Number Data for the Detection of Structural Variations Linked to a Disease Phenotype  

PubMed Central

Whilst the majority of inherited diseases have been found to be caused by single base substitutions, small insertions or deletions (<1Kb), a significant proportion of genetic variability is due to copy number variation (CNV). The possible role of CNV in monogenic and complex diseases has recently attracted considerable interest. However, until the development of whole genome, oligonucleotide micro-arrays, designed specifically to detect the presence of copy number variation, it was not easy to screen an individual for the presence of unknown deletions or duplications with sizes below the level of sensitivity of optical microscopy (3–5 Mb). Now that currently available oligonucleotide micro-arrays have in excess of a million probes, the problem of copy number analysis has moved from one of data production to that of data analysis. We have developed CNViewer, to identify copy number variation that co-segregates with a disease phenotype in small nuclear families, from genome-wide oligonucleotide micro-array data. This freely available program should constitute a useful addition to the diagnostic armamentarium of clinical geneticists.

Carr, Ian M.; Diggle, Christine P.; Khan, Kamron; Inglehearn, Chris; McKibbin, Martin; Bonthron, David T.; Markham, Alexander F.; Anwar, Rashida; Dobbie, Angus; Pena, Sergio D.J.; Ali, Manir

2012-01-01

222

Phenotypic Variation in Senescence in Miscanthus : Towards Optimising Biomass Quality and Quantity  

Microsoft Academic Search

Senescence impacts the harvestable biomass yield and quality in Miscanthus. Very early autumn senescence shortens the canopy duration reducing yield potential. When senescence is too late or slow,\\u000a the crop does not ripen sufficiently before harvest, resulting in high moisture and nutrient offtakes that reduce biomass\\u000a quality. In this study, variation in senescence was monitored over 3 years in a trial

Paul Robson; Michal Mos; John Clifton-Brown; Iain Donnison

223

Quantitative prediction of the effect of genetic variation using hidden Markov models  

PubMed Central

Background With the development of sequencing technologies, more and more sequence variants are available for investigation. Different classes of variants in the human genome have been identified, including single nucleotide substitutions, insertion and deletion, and large structural variations such as duplications and deletions. Insertion and deletion (indel) variants comprise a major proportion of human genetic variation. However, little is known about their effects on humans. The absence of understanding is largely due to the lack of both biological data and computational resources. Results This paper presents a new indel functional prediction method HMMvar based on HMM profiles, which capture the conservation information in sequences. The results demonstrate that a scoring strategy based on HMM profiles can achieve good performance in identifying deleterious or neutral variants for different data sets, and can predict the protein functional effects of both single and multiple mutations. Conclusions This paper proposed a quantitative prediction method, HMMvar, to predict the effect of genetic variation using hidden Markov models. The HMM based pipeline program implementing the method HMMvar is freely available at https://bioinformatics.cs.vt.edu/zhanglab/hmm.

2014-01-01

224

DNA variation in the phenotypically-diverse brown alga Saccharina japonica  

PubMed Central

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.

2012-01-01

225

The relationship between phenotypic variation among offspring and mother body mass in wild boar: evidence of coin-flipping?  

PubMed

1. In highly variable environments, the optimal reproductive tactics of iteroparous organisms should minimize variance in yearly reproductive success to maximize the long-term average reproductive success. To minimize among-year variation in reproductive success, individuals can either minimize the variance in the number of offspring produced at each reproductive attempt (classical bet-hedging) or maximize the phenotypic diversity of offspring produced within or among reproductive attempts (coin-flipping). 2. From a long-term detailed study of an intensively exploited population facing a highly unpredictable environment, we identify a continuum of reproductive tactics in wild boar females depending on their body mass. 3. At one end, light females adjusted litter size to their body mass and produced highly similar-sized offspring within a litter. These females fitted the hypothesis of individual optimization commonly reported in warm-blooded species, which involves both an optimal mass and an optimal number of offspring for a given mother. At the other end of the continuum, heavy females produced litters of variable size including a mixture of heavy and light offspring within litters. 4. Prolific heavy wild boar females diversify the phenotype of their offspring, providing a first evidence for coin-flipping in a warm-blooded species. PMID:23495696

Gamelon, Marlène; Gaillard, Jean-Michel; Baubet, Eric; Devillard, Sébastien; Say, Ludovic; Brandt, Serge; Gimenez, Olivier

2013-09-01

226

Phenotypic variation and host interactions of Xenorhabdus bovienii SS-2004, the entomopathogenic symbiont of Steinernema jollieti nematodes  

PubMed Central

Summary Xenorhabdus bovienii (SS-2004) bacteria reside in the intestine of the infective-juvenile (IJ) stage of the entomopathogenic nematode, Steinernema jollieti. The recent sequencing of the X. bovienii genome facilitates its use as a model to understand host-symbiont interactions. To provide a biological foundation for such studies, we characterized X. bovienii in vitro and host-interaction phenotypes. Within the nematode host X. bovienii was contained within a membrane bound envelope that also enclosed the nematode-derived intravesicular structure. S. jollieti nematodes cultivated on mixed lawns of X. bovienii expressing green or DsRed fluorescent proteins were predominantly colonized by one or the other strain, suggesting the colonizing population is founded by a few cells. X. bovienii exhibits phenotypic variation between orange-pigmented primary form and cream-pigmented secondary form. Each form can colonize IJ nematodes when cultured in vitro on agar. However, IJs did not develop or emerge from Galleria mellonella insects infected with secondary form. Unlike primary-form infected insects that were soft and flexible, secondary-form infected insects retained a rigid exoskeleton structure. X. bovienii primary and secondary form isolates are virulent toward Manduca sexta and several other insects. However, primary form stocks present attenuated virulence, suggesting that X. bovienii, like X. nematophila may undergo virulence modulation.

Sugar, Darby R.; Murfin, Kristen E.; Chaston, John M.; Andersen, Aaron W.; Richards, Gregory R.; deLeon, Limaris; Baum, James A.; Clinton, William P.; Forst, Steven; Goldman, Barry S.; Krasomil-Osterfeld, Karina C.; Slater, Steven; Stock, S. Patricia; Goodrich-Blair, Heidi

2011-01-01

227

Identification of reproductively isolated lineages of Amur grayling (Thymallus grubii Dybowski 1869): concordance between phenotypic and genetic variation.  

PubMed

We analysed variation at maternally (mitochondrial DNA control region sequences) and bi-parentally (10 microsatellites) inherited genetic markers, as well as across 12 meristic characters in 7 populations of Amur grayling, Thymallus grubii, from eastern Siberia. All three data sets were concordant in supporting the existence of three diagnosable, reciprocally monophyletic, and most probably reproductively isolated, lineages of grayling within the Amur drainage. There was a significant correlation between genetic and phenotypic divergence, both within and among lineages. Two phenotypically distinct forms (with and without an orange spot on the posterior portion of the dorsal fin), found in sympatry in the lower Amur, most likely result from secondary contact, as they demonstrate 4.6% sequence divergence at the mitochondrial DNA control region. This divergence, together with the existence of at least one nearby population of orange spot grayling outside the Amur drainage (0.8% divergence) underscore the palaeo-hydrological complexity of the system, which presumably promoted genetic divergence in a shifting allopatric framework throughout the Pleistocene. Grayling from the upper Amur, corresponding to the type locality for the species, formed a sister group (1.4-1.6% divergent) to the orange spot lineage perhaps diverging in the early Pleistocene (1.4-1.6 Ma). PMID:12919473

Froufe, E; Knizhin, I; Koskinen, M T; Primmer, C R; Weiss, S

2003-09-01

228

Physiological and morphological variation in Metrosideros polymorpha , a dominant Hawaiian tree species, along an altitudinal gradient: the role of phenotypic plasticity  

Microsoft Academic Search

Metrosideros polymorpha, a dominant tree species in Hawaiian ecosystems, occupies a wide range of habitats. Complementary field and common-garden\\u000a studies of M. polymorpha populations were conducted across an altitudinal gradient at two different substrate ages to ascertain if the large phenotypic\\u000a variation of this species is determined by genetic differences or by phenotypic modifications resulting from environmental\\u000a conditions. Several characteristics,

S. Cordell; G. Goldstein; D. Mueller-Dombois; D. Webb; P. M. Vitousek

1998-01-01

229

Variations in the Coding Region of the Agouti Signaling Protein Gene Do Not Explain Agouti\\/Non-agouti Phenotypes in Macaques  

Microsoft Academic Search

Agouti is a common pigmentation phenotype in mammals including primates. Mutations in the agouti signaling protein gene (ASIP) are known to result in non-agouti black hairs in laboratory mice. It is still unclear whether sequence variation in ASIP is linked with the agouti\\/non-agouti phenotypes in macaques (Genus Macaca). To address this issue, we have determined and compared nucleotide sequences of

Kazuhiro Nakayama; Takayoshi Shotake; Osamu Takeneka; Takafumi Ishida

2010-01-01

230

Genotypic and phenotypic variation among Lysobacter capsici strains isolated from Rhizoctonia suppressive soils.  

PubMed

Four Gram-negative bacterial strains, recovered from clay soils cultivated with different crops in the Netherland, were subjected to a polyphasic taxonomic study in order to clarify their taxonomic status. Comparative analysis of the 16S rRNA gene sequences revealed that they belong to the genus Lysobacter and to be highly related to the type strains of L. antibioticus DSM 2044(T), L. gummosus DSM 6980(T), and L. capsici DSM 19286(T), displaying 99.1-99.3%, 99.2-99.6% and 99.4-100% sequence similarities, respectively, to these species. The results of DNA-DNA hybridization studies unambigiously indicated that the four strains belonged to the species L. capsici. Nevertheless, DNA fingerprinting and phenotypic characterization indicated that there was a considerable diversification and niche differentiation among the strains belonging to L. capsici. The newly identified L. capsici strains strongly inhibit Rhizoctonia solani AG2 and originate from Rhizoctonia-suppressive soils where also populations of L. antibioticus and L. gummosus were present. This is the first report of the presence of combined populations of closely related Lysobacter spp. within agricultural soils. PMID:20399056

Postma, J; Nijhuis, E H; Yassin, A F

2010-06-01

231

Phenotypic and Genetic Variation in the Susceptibility of Haemophilus influenzae Type b to Antibodies to Somatic Antigens  

PubMed Central

Haemophilus influenzae type b (H.i.b) has been investigated with respect to phenotypic and genetic variations resulting in differential susceptibility to bactericidal antibody. Previous studies had shown that after growth in infected rats or in dialysate of rat serum, H.i.b strain Eag became more resistant to the bactericidal activity of antisomatic antibody. We now report that a similar phenotypic shift occurs when strain Eag is incubated with dialysate of human serum, that the increased resistance is to antibodies against determinants in the lipopolysaccharide not for the somatic antigens generally, and that most strains of H.i.b undergo the shift. To assess genetic differences in exposed antigens, a panel of 13 H.i.b isolates from cerebrospinal fluid were analyzed with cross-adsorbed antisera. Seven different patterns were found that could be accounted for through the variable expression of six antigens. These ranged from infrequent (found on 1:13 strains) to common (10:13 strains). At least four were somatic rather than capsular determinants; the most common (antigen 1) was contained in lipopolysaccharide. The epidemiologic relevance of the genetic variations was explored using pairs of isolates from two children who had had two documented infections with H.i.b. In both cases the isolates varied in somatic antigen expression. The strains from one patient differed in the expression of antigen 1. The isolates from the other were indistinguishable in sub-typing for the six classified antigens, but differed in the expression of an additional antigen identified by use of the patient's serum.

Anderson, Porter; Flesher, Alan; Shaw, Stephen; Harding, A. Lynn; Smith, David H.

1980-01-01

232

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

PubMed Central

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.

2014-01-01

233

Phenotypic plasticity in Pinus pinaster ? 13 C: environment modulates genetic variation  

Microsoft Academic Search

– \\u000a \\u000a • Carbon isotope composition (?13C) is a complex trait involved in acclimation, adaptive processes and related to water use efficiency (WUE) and\\/or productivity.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a • To estimate the genetic variation in ?13C and growth (h), their relationship, and the genotype by environment interaction effect in both variables, we analyzed three Pinus pinaster populations and six to ten families per

Leyre Corcuera; Eustaquio Gil-Pelegrin; Eduardo Notivol

2010-01-01

234

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

PubMed Central

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 QTL might be sex-specific. Bone structure at the proximal femur was measured in 205 pairs of brothers age 18–61. Heritability was calculated and linkage analysis performed on phenotypes at the proximal femur. Heritability estimates ranged from 0.99 to 0.39. A genome wide scan identified suggestive QTL (LOD>2.2) for femoral shaft width on chromosome 14q (LOD=2.69 at position 99cM), calcar femorale at chromosome 2p (LOD= 3.97 at position 194cM) and at the X chromosome (LOD= 3.01 at position 77cM), femoral neck width on chromosome 5p (LOD=2.28 at position 0 cM), femoral head width on chromosome 11q (LOD=2.30 at position 131 cM) and 15q (LOD=3.11 at position 90 cM), and pelvic axis length on chromosome 4q (LOD= 4.16 at 99cM) and 17q (LOD=2.80 at position 112 cM). Comparison with published data in 437 pairs of premenopausal sisters from the same geographical region suggested that 3 of the 7 autosomal QTL were male-specific. This study demonstrates that bone structure at the proximal femur in healthy men is highly heritable. The occurrence of sex-specific genes in humans for bone structure has important implications for the pathogenesis and treatment of osteoporosis.

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

2006-01-01

235

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

PubMed Central

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.

2014-01-01

236

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

SciTech Connect

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.

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

237

Quantitative trait loci affecting phenotypic plasticity and the allometric relationship of ovariole number and thorax length in Drosophila melanogaster.  

PubMed

Environmental factors during juvenile growth such as temperature and nutrition have major effects on adult morphology and life-history traits. In Drosophila melanogaster, ovary size, measured as ovariole number, and body size, measured as thorax length, are developmentally plastic traits with respect to larval nutrition. Herein we investigated the genetic basis for plasticity of ovariole number and body size, as well the genetic basis for their allometric relationship using recombinant inbred lines (RILs) derived from a natural population in Winters, California. We reared 196 RILs in four yeast concentrations and measured ovariole number and body size. The genetic correlation between ovariole number and thorax length was positive, but the strength of this correlation decreased with increasing yeast concentration. Genetic variation and genotype-by-environment (G x E) interactions were observed for both traits. We identified quantitative trait loci (QTL), epistatic, QTL-by-environment, and epistatic-by-environment interactions for both traits and their scaling relationships. The results are discussed in the context of multivariate trait evolution. PMID:18716336

Bergland, Alan O; Genissel, Anne; Nuzhdin, Sergey V; Tatar, Marc

2008-09-01

238

Daily stress reactivity and serotonin transporter gene (5-HTTLPR) variation: internalizing responses to everyday stress as a possible transdiagnostic phenotype  

PubMed Central

Background Recent studies examining the interaction between the 5-HTTLPR locus in the serotonin transporter gene and life stress in predicting depression have yielded equivocal results, leading some researchers to question whether 5-HTTLPR variation indeed regulates depressive responses to stress. Two possible sources of inconsistent data in this literature are imprecise stress assessment methodologies and a restricted focus on depression phenotypes as the outcome of interest, as opposed to transdiagnostic emotional symptoms such as internalizing and externalizing dimensions. The present study aimed to address these critical limitations in prior research by examining how 5-HTTLPR acts in concert with idiographically assessed daily life stress to predict transdiagnostic emotional outcomes. Results One hundred and four healthy young adults genotyped for 5-HTTLPR reported on their life stress exposure and internalizing and externalizing experiences for 14 consecutive days. As hypothesized, daily stress levels were associated with severity of internalizing symptoms, but only for 5-HTTLPR S allele carriers. Additional analyses revealed that these interactive effects of 5-HTTLPR and daily life stress on internalizing symptoms extended to both the distress and fear subdomains of internalizing symptoms. Conclusions Considered together, these results support the validity of the 5-HTTLPR stress sensitivity hypothesis and suggest for the first time that variation at 5-HTTLPR moderates the effects of daily life stress on broadband symptom profiles.

2014-01-01

239

Quantitative genetic variation in an island population of the speckled wood butterfly (Pararge aegeria).  

PubMed

Evidence of changes in levels of genetic variation in the field is scarce. Theoretically, selection and a bottleneck may lead to the depletion of additive genetic variance (V(A)) but not of nonadditive, dominance variance (V(D)), although a bottleneck may converse V(D) to V(A). Here we analyse quantitative genetic variation for the Speckled Wood butterfly Pararge aegeria on the island of Madeira about 120 generations after first colonisation. Colonisation of the island involved both a bottleneck and strong natural selection, changing the average value of traits. Several life history and morphological traits with varying levels of change since colonisation were analysed. In accordance with expectations, all traits except one showed relatively low levels of V(A), with an average heritability (h(2)) of 0.078. Levels of V(D) for these traits were relatively high, 20-94% of total variance and on average 80% of V(G). The exception was a morphological trait that probably had not experienced strong natural selection after colonisation, for which a h(2) of 0.27 was found. Another interesting observation is that the population seems resistant to inbreeding effects, which may be the result of purging of deleterious alleles. PMID:15254491

Windig, J J; Veerkamp, R F; Nylin, S

2004-11-01

240

Multivariate stabilizing selection and pleiotropy in the maintenance of quantitative genetic variation.  

PubMed

We investigate maintenance of quantitative genetic variation at mutation-selection balance for multiple traits. The intrinsic strength of real stabilizing selection on one of these traits denoted the "target trait" and the observed strength of apparent stabilizing selection on the target trait can be quite different: the latter, which is estimable, is much smaller (i.e., implying stronger selection) than the former. Distinguishing them may enable the mutation load to be relaxed when considering multivariate stabilizing selection. It is shown that both correlations among mutational effects and among strengths of real stabilizing selection on the traits are not important unless they are high. The analysis for independent situations thus provides a good approximation to the case where mutant and stabilizing selection effects are correlated. Multivariate stabilizing selection can be regarded as a combination of stabilizing selection on the target trait and the pleiotropic direct selection on fitness that is solely due to the effects of real stabilizing selection on the hidden traits. As the overall fitness approaches a constant value as the number of traits increases, multivariate stabilizing selection can maintain abundant genetic variance only under quite weak selection. The common observations of high polygenic variance and strong stabilizing selection thus imply that if the mutation-selection balance is the true mechanism of maintenance of genetic variation, the apparent stabilizing selection cannot arise solely by real stabilizing selection simultaneously on many metric traits. PMID:14503618

Zhang, Xu-Sheng; Hill, William G

2003-08-01

241

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

PubMed

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

Wayne, M L; Mackay, T F

1998-01-01

242

Quantitative Estimation of Temperature Variations in Plantar Angiosomes: A Study Case for Diabetic Foot  

PubMed Central

Thermography is a useful tool since it provides information that may help in the diagnostic of several diseases in a noninvasive and fast way. Particularly, thermography has been applied in the study of the diabetic foot. However, most of these studies report only qualitative information making it difficult to measure significant parameters such as temperature variations. These variations are important in the analysis of the diabetic foot since they could bring knowledge, for instance, regarding ulceration risks. The early detection of ulceration risks is considered an important research topic in the medicine field, as its objective is to avoid major complications that might lead to a limb amputation. The absence of symptoms in the early phase of the ulceration is conceived as the main disadvantage to provide an opportune diagnostic in subjects with neuropathy. Since the relation between temperature and ulceration risks is well established in the literature, a methodology that obtains quantitative temperature differences in the plantar area of the diabetic foot to detect ulceration risks is proposed in this work. Such methodology is based on the angiosome concept and image processing.

Peregrina-Barreto, H.; Morales-Hernandez, L. A.; Rangel-Magdaleno, J. J.; Avina-Cervantes, J. G.; Ramirez-Cortes, J. M.; Morales-Caporal, R.

2014-01-01

243

Genomic and phenotypic variation in epidemic-spanning Salmonella enterica serovar Enteritidis isolates  

PubMed Central

Background Salmonella enterica serovar Enteritidis (S. Enteritidis) has caused major epidemics of gastrointestinal infection in many different countries. In this study we investigate genome divergence and pathogenic potential in S. Enteritidis isolated before, during and after an epidemic in Uruguay. Results 266 S. Enteritidis isolates were genotyped using RAPD-PCR and a selection were subjected to PFGE analysis. From these, 29 isolates spanning different periods, genetic profiles and sources of isolation were assayed for their ability to infect human epithelial cells and subjected to comparative genomic hybridization using a Salmonella pan-array and the sequenced strain S. Enteritidis PT4 P125109 as reference. Six other isolates from distant countries were included as external comparators. Two hundred and thirty three chromosomal genes as well as the virulence plasmid were found as variable among S. Enteritidis isolates. Ten out of the 16 chromosomal regions that varied between different isolates correspond to phage-like regions. The 2 oldest pre-epidemic isolates lack phage SE20 and harbour other phage encoded genes that are absent in the sequenced strain. Besides variation in prophage, we found variation in genes involved in metabolism and bacterial fitness. Five epidemic strains lack the complete Salmonella virulence plasmid. Significantly, strains with indistinguishable genetic patterns still showed major differences in their ability to infect epithelial cells, indicating that the approach used was insufficient to detect the genetic basis of this differential behaviour. Conclusion The recent epidemic of S. Enteritidis infection in Uruguay has been driven by the introduction of closely related strains of phage type 4 lineage. Our results confirm previous reports demonstrating a high degree of genetic homogeneity among S. Enteritidis isolates. However, 10 of the regions of variability described here are for the first time reported as being variable in S. Enteritidis. In particular, the oldest pre-epidemic isolates carry phage-associated genetic regions not previously reported in S. Enteritidis. Overall, our results support the view that phages play a crucial role in the generation of genetic diversity in S. Enteritidis and that phage SE20 may be a key marker for the emergence of particular isolates capable of causing epidemics.

2009-01-01

244

Phenotypic Variation in Dentinogenesis Imperfecta/Dentin Dysplasia Linked to 4q21  

PubMed Central

Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders that primarily affect the formation of tooth dentin. Both conditions are autosomal-dominant and can be caused by mutations in the dentin sialophospho-protein gene (DSPP, 4q21.3). We recruited 23 members of a four-generation kindred, including ten persons with dentin defects, and tested the hypothesis that these defects are linked to DSPP. The primary dentition showed amber discoloration, pulp obliteration, and severe attrition. The secondary dentition showed either pulp obliteration with bulbous crowns and gray discoloration or thistle-tube pulp configurations, normal crowns, and mild gray discoloration. Haplotype analyses showed no recombination between three 4q21-q24 markers and the disease locus. Mutational analyses identified no coding or intron junction sequence variations associated with affection status in DMP1, MEPE, or the DSP portion of DSPP. The defects in the permanent dentition were typically mild and consistent with a diagnosis of DD-II, but some dental features associated with DGI-II were also present. We conclude that DD-II and DGI-II are milder and more severe forms, respectively, of the same disease.

Beattie, M.L.; Kim, J.-W.; Gong, S.-G.; Murdoch-Kinch, C.A.; Simmer, J.P.; Hu, J.C.-C.

2008-01-01

245

Familial concordance of phenotype and microbial variation among siblings with CF.  

PubMed

The clinical spectrum of cystic fibrosis (CF) is influenced by the cystic fibrosis transmembrane conductance regulator (CFTR) genotype. However, variable courses of the disease were demonstrated among patients with identical genotypes. Since siblings share identical CFTR mutations and environmental factors, they can serve as a model to assess the effect of modifier genes on disease expression, and also to evaluate cross-infection. The aim of this study was to compare disease expression among siblings with CF. All sibling pairs treated at 7 CF centers in Israel were included in the study. Data were collected from patients' medical charts. Fifty families with at least 2 siblings were identified. As expected, the second-born sibling was diagnosed at an earlier age compared to the first-born. The mode of CF presentation at diagnosis showed significant familial concordance. In the families where the first sibling presented with gastrointestinal manifestations, 79% of the second siblings also presented with gastrointestinal manifestations. When gastrointestinal manifestations were absent in the first sibling, only 12% of the second siblings presented with gastrointestinal manifestations (P < 0.0001). Likewise, when the first sibling presented with respiratory symptoms, 60% of the second siblings presented with the similar symptoms. However, when the first sibling presented without respiratory symptoms, only 12% of the second siblings presented with respiratory symptoms (P < 0.001). Meconium ileus (MI) was present in 20 patients (21%). In 10 families where the first-born sibling had MI, 8 (80%) of the subsequent siblings had MI. On the other hand, in the 39 families where the first-born sibling did not have MI, only 2 (5%) subsequent siblings had MI (P < 0.001). Pancreatic insufficiency (PI) also had high familial concordance (P < 0.0001). Percentile growth for weights and heights and lung function (FVC, FEV(1), and FEF(25-75)) at ages 7 and 10 years were similar between siblings. P. aeruginosa grew from sputum in 89% of our study patients. When P. aeruginosa was isolated from the first-born patient, 91% of the second siblings were also positive for P. aeruginosa, whereas when the initial sibling was not a carrier of P. aeruginosa, only 50% of subsequent siblings were positive (P < 0.0001). This familial concordance was not observed for S. aureus. By contrast, the age of first isolation of P. aeruginosa and S. aureus was significantly earlier in the second sibling than in the first for the two bacteria: 10.3 +/- 5.1 vs. 7.3 +/- 5.2 years (P < 0.05) for P. aeruginosa, and 11.5 +/- 5.4 years vs. 6.8 +/- 5.1 years (P < 0.05) for S. aureus. CF siblings tend to share similar phenotypes that are not mutation-dependent. The lack of variability between siblings in mode of initial CF presentation, rates of MI, pulmonary function, and nutritional status supports the role of modifier genes in the determination of these factors. PMID:15334505

Picard, Elie; Aviram, Micha; Yahav, Yaakov; Rivlin, Joseph; Blau, Hanna; Bentur, Lea; Avital, Avraham; Villa, Yael; Schwartz, Shepard; Kerem, Batsheva; Kerem, Eitan

2004-10-01

246

Geographic and phenotypic variation in heartwood and essential-oil characters in natural populations of Santalum austrocaledonicum in Vanuatu.  

PubMed

Phenotypic variation in heartwood and essential-oil characters of Santalum austrocaledonicum was assessed across eleven populations on seven islands of Vanuatu. Trees differed significantly in their percentage heartwood cross-sectional area and this varied independently of stem diameter. The concentrations of the four major essential-oil constituents (alpha-santalol, beta-santalol, (Z)-beta-curcumen-12-ol, and cis-nuciferol) of alcohol-extracted heartwood exhibited at least tenfold and continuous tree-to-tree variation. Commercially important components alpha- and beta-santalol found in individual trees ranged from 0.8-47% and 0-24.1%, respectively, across all populations, and significant (P<0.05) differences for each were found between individual populations. The Erromango population was unique in that the mean concentrations of its monocyclic ((Z)-beta-curcumen-12-ol and cis-nuciferol) sesquiterpenes exceeded those of its bi- and tricyclic (alpha- and beta-santalol) sesquiterpenes. Heartwood colour varied between trees and spanned 65 colour categories, but no identifiable relationships were found between heartwood colour and alpha- and beta-santalol, although a weak relationship was evident between colour saturation and total oil concentration. These results indicate that the heartwood colour is not a reliable predictive trait for oil quality. The results of this study highlight the knowledge gaps in fundamental understanding of heartwood biology in Santalum genus. The intraspecific variation in heartwood cross-sectional area, oil concentration, and oil quality traits is of considerable importance to the domestication of sandalwood and present opportunities for the development of highly superior S. austrocaledonicum cultivars that conform to the industry's International Standards used for S. album. PMID:20730962

Page, Tony; Southwell, Ian; Russell, Mike; Tate, Hanington; Tungon, Joseph; Sam, Chanel; Dickinson, Geoff; Robson, Ken; Leakey, Roger R B

2010-08-01

247

Genome-wide linkage scan for quantitative trait loci underlying normal variation in heel bone ultrasound measures  

Microsoft Academic Search

Quantitative ultrasound (QUS) traits are correlated with bone mineral density (BMD), but predict risk for future fracture\\u000a independent of BMD. Only a few studies, however, have sought to identify specific genes influencing calcaneal QUS measures.\\u000a The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing normal\\u000a variation in QUS traits. QUS

Miryoung Lee; A. C. Choh; K. D. Williams; V. Schroeder; T. D. Dyer; J. Blangero; S. A. Cole; Wm. C. Chumlea; D. L. Duren; R. J. Sherwood; R. M. Siervogel; B. Towne; S. A. Czerwinski

248

Genetic and phenotypic variation of Fusarium proliferatum isolates from different host species.  

PubMed

Fusarium proliferatum (Matsushima) Nirenberg is a common pathogen infecting numerous crop plants and occurring in various climatic zones. It produces large amounts of fumonisins, a group of polyketide-derived mycotoxins. Fumonisin biosynthesis is determined by the presence and activity of the FUM cluster, several co-regulated genes with a common expression pattern. In the present work, we analyzed 38 F. proliferatum isolates from different host plant species, demonstrating host-specific polymorphisms in partial sequences of the key FUM1 gene (encoding polyketide synthase). We also studied growth rates across different temperatures and sample origin and tried to establish the relationships between DNA sequence polymorphism and toxigenic potential. Phylogenetic analysis was conducted based on FUM1 and tef-1? sequences for all isolates. The results indicated the greatest variations of both toxigenic potential and growth patterns found across the wide selection of isolates derived from maize. Fumonisin production for maize isolates ranged from 3.74 to 4,500 ?g/g of fumonisin B(1). The most efficient producer isolates obtained from other host plants were only able to synthesize 1,820-2,419 ?g/g of this metabolite. A weak negative rank correlation between fumonisin content and isolate growth rates was observed. All garlic-derived isolates formed a distinct group on a FUM1-based dendrogram. A second clade consisted of tropical and sub-tropical strains (isolated from pineapple and date palm). Interestingly, isolates with the fastest growth patterns were also grouped together and included both isolates originating from rice. The sequence of the FUM1 gene was found to be useful in revealing the intraspecific polymorphism, which is, to some extent, specifically correlated with the host plant. PMID:21796391

St?pie?, Lukasz; Koczyk, Grzegorz; Wa?kiewicz, Agnieszka

2011-11-01

249

Copy number variations of MICAL-L2 shaping gene expression contribute to different phenotypes of cattle.  

PubMed

Copy number variations (CNVs) recently have been recognized as an important source of genetic variability. Compelling evidence has indicated that CNVs are responsible for phenotypic traits by altering the copy numbers of functional genes. The molecule interacting with CasL-like protein 2 (MICAL-L2) gene plays a critical role in muscle fiber development and has been identified in the CNV region by comparative genomic hybridization array. In the present study, we detected the different distributions of MICAL-L2 gene copy numbers in four Chinese cattle breeds (QC, NY, LX, and CY) and investigated the functional effects of MICAL-L2 CNVs on the gene's expression level and the phenotypic traits in QC and NY cattle. The results showed that the copy number loss (relative to Angus cattle) was more frequent in CY than in the other breeds. The MICAL-L2 gene copy number presented a moderate negative correlation with the transcriptional expression in fetal skeletal muscles (P < 0.05). Statistical analysis revealed that the MICAL-L2 CNVs were significantly associated with body weight, body height, and body length of NY cattle in the early stages (6 and 12 months old), and the copy number loss showed better traits than the gain and/or median groups (P < 0.05). No significance was found at the late stages in QC (24 months old) and NY cattle (18 and 24 months old). These observations provided further insight into the associations between cattle CNVs and economic traits, suggesting that the CNVs may be considered promising markers for the molecular breeding of Chinese beef cattle. PMID:24196410

Xu, Yao; Zhang, Liangzhi; Shi, Tao; Zhou, Yang; Cai, Hanfang; Lan, Xianyong; Zhang, Chunlei; Lei, Chuzhao; Chen, Hong

2013-12-01

250

Quantitative NMR Metabolite Profiling of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Discriminates between Biofilm and Planktonic Phenotypes.  

PubMed

Wound bioburden in the form of colonizing biofilms is a major contributor to nonhealing wounds. Staphylococcus aureus is a Gram-positive, facultative anaerobe commonly found in chronic wounds; however, much remains unknown about the basic physiology of this opportunistic pathogen, especially with regard to the biofilm phenotype. Transcriptomic and proteomic analysis of S. aureus biofilms have suggested that S. aureus biofilms exhibit an altered metabolic state relative to the planktonic phenotype. Herein, comparisons of extracellular and intracellular metabolite profiles detected by (1)H NMR were conducted for methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus strains grown as biofilm and planktonic cultures. Principal component analysis distinguished the biofilm phenotype from the planktonic phenotype, and factor loadings analysis identified metabolites that contributed to the statistical separation of the biofilm from the planktonic phenotype, suggesting that key features distinguishing biofilm from planktonic growth include selective amino acid uptake, lipid catabolism, butanediol fermentation, and a shift in metabolism from energy production to assembly of cell-wall components and matrix deposition. These metabolite profiles provide a basis for the development of metabolite biomarkers that distinguish between biofilm and planktonic phenotypes in S. aureus and have the potential for improved diagnostic and therapeutic use in chronic wounds. PMID:24809402

Ammons, Mary Cloud B; Tripet, Brian P; Carlson, Ross P; Kirker, Kelly R; Gross, Michael A; Stanisich, Jessica J; Copié, Valérie

2014-06-01

251

The Strength of Phenotypic Selection in Natural Populations  

Microsoft Academic Search

How strong is phenotypic selection on quantitative traits in the wild? We reviewed the literature from 1984 through 1997 for studies that estimated the strength of linear and quadratic selection in terms of standardized selection gradients or differentials on natural variation in quantitative traits for field populations. We tabulated 63 published studies of 62 species that reported over 2,500 estimates

J. G. Kingsolver; H. E. Hoekstra; J. M. Hoekstra; D. Berrigan; S. N. Vignieri; C. E. Hill; A. Hoang; P. Gibert; P. Beerli

2001-01-01

252

The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation  

Microsoft Academic Search

The melanocortin 1 receptor (MC1R) is known to play an important role in determining physiological variation in human pigmentation, and consequently human susceptibility to ultraviolet radiation. A reason for wider interest is that the considerable phenotypic diversity has been in part generated by the effects of gene dosage, and the presence of a large number of mutations at this G-protein

Terence Hawkin Wong; Jonathan Laurence Rees

2005-01-01

253

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

PubMed

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

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

2014-05-01

254

Quantitative ultrasound imaging of the calcaneus: precision and variations during a 120-Day bed rest.  

PubMed

This study reports on the precision and variation of quantitative ultrasound (US) parameters [broadband ultrasonic attenuation (BUA) or slope of the frequency-dependent attenuation in dB/MHz and speed of sound (SOS m/second)] after 120 days of continuous bed rest in six normal male volunteers. Quantitative US was measured at the calcaneus using a new US bone imaging scanner. The measurements were carried out on both heels at approximately 2-week intervals. The short-term precision was 0.31% for SOS and 2.8% for BUA. The long-term precision was 0.58% for SOS, 4.7% for BUA. A significant decrease of SOS values of -26 m/second (P < 0.0001) for the right heel and -17 m/second (P < 0.05) for the left heel was found at the group level. In terms of percentage change this represents -1.7% for the right heel and -1.1% for the left heel. These percentage decrements were 3.5-5.5 times that of the short-term precision and 2-3 times that of the long-term precision of the technique. At the individual level, the decrease of SOS was statistically significant (P < 0.05) or marginally significant (P < 0.1) for four out of 6 subjects. For 2 other subjects, similar trends were observed, but without reaching statistical significance. BUA did not change significantly during follow-up. These results are consistent with previous findings on changes of ultrasonic properties from the calcaneus during aging, pregnancy, or therapy, showing that calcaneus SOS is a valuable index of bone loss. These preliminary data suggest that prolonged exposure to simulated weightlessness may lead to a lower SOS, which then could be used for the follow-up of bone demineralization occurring during long-term space flights. PMID:10602839

Laugier, P; Novikov, V; Elmann-Larsen, B; Berger, G

2000-01-01

255

Variation in Estrogen-Related Genes Associated with Cardiovascular Phenotypes and Circulating Estradiol, Testosterone, and Dehydroepiandrosterone Sulfate Levels  

PubMed Central

Background: Younger age at the onset of menopause and lower circulating levels of estrogen are risk factors for cardiovascular disease. Several studies have detected associations between variations in genes encoding estrogen receptors ? (ESR1) and ? (ESR2), and enzyme aromatase (CYP19A1), which regulates the estrogen to testosterone ratio, and cardiovascular phenotypes in the Framingham Heart Study. To explore potential mechanisms by which these gene variants may contribute to cardiovascular disease, we tested the hypothesis that the polymorphisms were associated with endogenous steroid hormone levels. Methods: Multiple regression analysis was used to assess the relation between reported polymorphisms and total serum estradiol, testosterone, and dehydroepiandrosterone sulfate levels in 834 men and 687 women who attended the third and fourth Framingham Heart Study examination cycles. Results: In men, significant associations were detected between CYP19A1 polymorphisms and estradiol and testosterone levels, and the estradiol to testosterone ratio (P ranges 0.0005–0.01). Specifically, carriers of common haplotype rs700518[G]-(TTTA)n [L]-rs726547[C] had higher estradiol levels (5% per copy; P = 0.0004), lower testosterone levels (17% per copy; P = 0.036), and a higher estradiol to testosterone ratio (24% per copy; P < 0.0001) compared with the rs700518[A]-(TTTA)n [S]-rs726547[C] carriers. In addition, postmenopausal carriers of the ESR2 (CA)n long allele and rs1256031 [C] allele had moderately higher estradiol levels (P ? 0.03). No significant associations with the ESR1 variants were detected. Conclusions: Our findings suggest that variations in CYP19A1 correlate with steroid hormone levels in men. Knowledge that a specific carrier status may predispose to altered steroid hormone levels may lead to targeted intervention strategies to reduce health risks in genetically susceptible individuals.

Peter, Inga; Kelley-Hedgepeth, Alyson; Fox, Caroline S.; Adrienne Cupples, L.; Huggins, Gordon S.; Housman, David E.; Karas, Richard H.; Mendelsohn, Michael E.; Levy, Daniel; Murabito, Joanne M.

2008-01-01

256

Qualitative and Quantitative Variation in Monoterpene Co-Occurrence and Composition in the Essential Oil of Thymus vulgaris Chemotypes  

Microsoft Academic Search

Thymus vulgaris has a chemical polymorphism with six different chemotypes that show marked spatial segregation in nature. Although some populations have a single chemotype in majority, many have two or three chemotypes. In this study we analyze the quantitative variation among T. vulgaris populations in the percentage of oil composed of the dominant monoterpene(s) for each chemotype. In general, phenolic

John D. Thompson; Jean-Claude Chalchat; ANDR ´ E MICHET; Yan B. Linhart; Bodil Ehlers

2003-01-01

257

Quantitative genetic variation for thermal performance curves within and among natural populations of Drosophila serrata.  

PubMed

Thermal performance curves (TPCs) provide a powerful framework for studying the evolution of continuous reaction norms and for testing hypotheses of thermal adaptation. Although featured heavily in comparative studies, the framework has been comparatively underutilized for quantitative genetic tests of thermal adaptation. We assayed the distribution of genetic (co)variance for TPC (locomotor activity) within and among three natural populations of Drosophila serrata and performed replicated tests of two hypotheses of thermal adaptation--that 'hotter is better' and that a generalist-specialist trade-off underpins the evolution of thermal sensitivity. We detected significant genetic variance within, and divergence among, populations. The 'hotter is better' hypothesis was not supported as the genetic correlations between optimal temperature (T(opt)) and maximum performance (z(max)) were consistently negative. A pattern of variation consistent with a generalist-specialist trade-off was detected within populations and divergence among populations indicated that performance curves were narrower and had higher optimal temperatures in the warmer, but less variable tropical population. PMID:21306462

Latimer, C A L; Wilson, R S; Chenoweth, S F

2011-05-01

258

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

PubMed Central

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.

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

2012-01-01

259

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

PubMed

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

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

2012-06-01

260

Quantitative Assessment of Autism Symptom-Related Traits in Probands and Parents: Broader Phenotype Autism Symptom Scale  

ERIC Educational Resources Information Center

Autism susceptibility genes likely have effects on continuously distributed autism-related traits, yet few measures of such traits exist. The Broader Phenotype Autism Symptom Scale (BPASS), developed for use with affected children and family members, measures social motivation, social expressiveness, conversational skills, and flexibility. Based…

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

2007-01-01

261

Rapid Publication PhenoChipping of Psychotic Disorders: A Novel Approach for Deconstructing and Quantitating Psychiatric Phenotypes  

Microsoft Academic Search

Psychiatric phenotypes as currently defined are primarily the result of clinical consensus criteria rather than empirical research. We propose, and present initial proof of principle for, a novel approach to characterizing psychiatric pheno- types. We have termed our approach PhenoChip- ping, by analogy with, and borrowing paradigms and tools from, gene expression microarray studies (GeneChipping). A massive parallel profil- ing

Alexander B. Niculescu; Len L. Lulow; Corey A. Ogden; Helen Le-Niculescu; Daniel R. Salomon; Nicholas J. Schork; Michael P. Caligiuri; James B. Lohr

262

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

PubMed

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

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

2006-06-01

263

Combination of differential growth at two different temperatures with a quantitative real-time polymerase chain reaction to determine temperature-sensitive phenotype of Mycoplasma synoviae.  

PubMed

Mycoplasma synoviae infections result in significant economic losses in the chicken and turkey industries. A commercially available live temperature-sensitive (ts (+)) vaccine strain MS-H has been found to be effective in controlling M. synoviae infections in commercial layer and broiler breeder farms in various countries, including Australia. Detection and differentiation of MS-H from field strains (ts (-)) and from ts (-) MS-H reisolates in vaccinated flocks is vital in routine flock status monitoring. At present microtitration is the only available technique to determine the ts phenotype of M. synoviae. This technique is time consuming and not amenable to automation. In the present study, a quantitative real-time polymerase chain reaction (Q-PCR) was combined with simultaneous culturing of M. synoviae at two different temperatures (33°C and 39.5°C) to determine the ts phenotype of 22 Australian M. synoviae strains/isolates. The M. synoviae type strain WVU-1853 was also included for comparison. A ratio of the copy numbers of the variable lipoprotein haemagglutinin (vlhA) gene at the two temperatures was calculated and a cut-off value was determined and used to delineate the ts phenotype. In all M. synoviae strains/isolates tested in this study, the ts phenotype determined using Q-PCR was in agreement with that determined using conventional microtitration. Combination of Q-PCR with differential growth at two different temperatures is a rapid, reliable and accurate technique that could be used as an effective tool in laboratories actively involved in ts phenotyping of M. synoviae strains/isolates. PMID:23581447

Shahid, Muhammad A; Ghorashi, Seyed A; Agnew-Crumpton, Rebecca; Markham, Philip F; Marenda, Marc S; Noormohammadi, Amir H

2013-04-01

264

Genetic variations and humoral immune responses to myelin oligodendroglia glycoprotein in adult phenotypes of X-linked adrenoleukodystrophy  

Microsoft Academic Search

The lack of phenotype\\/genotype association in X-linked adrenoleukodystrophy (X-ALD) has prompted the search for disease modifying factors. We previously demonstrated increased serum antibody responses against myelin oligodendrocyte glycoprotein (MOG) in various clinical phenotypes of X-ALD allowing speculations that myelin specific humoral immune responses might be involved in phenotype generation of X-ALD. In the present study, we investigated the possible association

Stephan Schmidt; Giovanna Maria Marrosu; Heike Kölsch; Claus G. Haase; Stanislav Ferenczik; Piotr Sokolowski; Wolfgang Köhler; Martina Schmidt; Andreas Papassotiropoulos; Reinhard Heun; Hans Grosse-Wilde; Thomas Klockgether

2003-01-01

265

Deleterious Mutations, Apparent Stabilizing Selection and the Maintenance of Quantitative Variation  

PubMed Central

Apparent stabilizing selection on a quantitative trait that is not causally connected to fitness can result from the pleiotropic effects of unconditionally deleterious mutations, because as N. Barton noted, ``... individuals with extreme values of the trait will tend to carry more deleterious alleles ....'' We use a simple model to investigate the dependence of this apparent selection on the genomic deleterious mutation rate, U; the equilibrium distribution of K, the number of deleterious mutations per genome; and the parameters describing directional selection against deleterious mutations. Unlike previous analyses, we allow for epistatic selection against deleterious alleles. For various selection functions and realistic parameter values, the distribution of K, the distribution of breeding values for a pleiotropically affected trait, and the apparent stabilizing selection function are all nearly Gaussian. The additive genetic variance for the quantitative trait is kQa(2), where k is the average number of deleterious mutations per genome, Q is the proportion of deleterious mutations that affect the trait, and a(2) is the variance of pleiotropic effects for individual mutations that do affect the trait. In contrast, when the trait is measured in units of its additive standard deviation, the apparent fitness function is essentially independent of Q and a(2); and ?, the intensity of selection, measured as the ratio of additive genetic variance to the ``variance'' of the fitness curve, is very close to s = U/k, the selection coefficient against individual deleterious mutations at equilibrium. Therefore, this model predicts appreciable apparent stabilizing selection if s exceeds about 0.03, which is consistent with various data. However, the model also predicts that ? must equal V(m)/V(G), the ratio of new additive variance for the trait introduced each generation by mutation to the standing additive variance. Most, although not all, estimates of this ratio imply apparent stabilizing selection weaker than generally observed. A qualitative argument suggests that even when direct selection is responsible for most of the selection observed on a character, it may be essentially irrelevant to the maintenance of variation for the character by mutation-selection balance. Simple experiments can indicate the fraction of observed stabilizing selection attributable to the pleiotropic effects of deleterious mutations.

Kondrashov, A. S.; Turelli, M.

1992-01-01

266

The effect of temperature and wing morphology on quantitative genetic variation in the cricket Gryllus firmus, with an appendix examining the statistical properties of the Jackknife-MANOVA method of matrix comparison.  

PubMed

We investigated the effect of temperature and wing morphology on the quantitative genetic variances and covariances of five size-related traits in the sand cricket, Gryllus firmus. Micropterous and macropterous crickets were reared in the laboratory at 24, 28 and 32 degrees C. Quantitative genetic parameters were estimated using a nested full-sib family design, and (co)variance matrices were compared using the T method, Flury hierarchy and Jackknife-manova method. The results revealed that the mean phenotypic value of each trait varied significantly among temperatures and wing morphs, but temperature reaction norms were not similar across all traits. Micropterous individuals were always smaller than macropterous individuals while expressing more phenotypic variation, a finding discussed in terms of canalization and life-history trade-offs. We observed little variation between the matrices of among-family (co)variation corresponding to each combination of temperature and wing morphology, with only one matrix of six differing in structure from the others. The implications of this result are discussed with respect to the prediction of evolutionary trajectories. PMID:15525410

Bégin, M; Roff, D A; Debat, V

2004-11-01

267

Quantitative proteomic profiling reveals photosynthesis responsible for inoculum size dependent variation in Chlorella sorokiniana.  

PubMed

High density cultivation is essential to industrial production of biodiesel from microalgae, which involves in variations of micro-environment around individual cells, including light intensity, nutrition distribution, other abiotic stress and so on. To figure out the main limit factor in high inoculum cultivation, a quantitative proteomic analysis (iTRAQ-on-line 2-D nano-LC/MS) in a non-model green microalga, Chlorella sorokiniana, under different inoculum sizes was conducted. The resulting high-quality proteomic dataset consisted of 695 proteins. Using a cutoff of P < 0.05, 241 unique proteins with differential expression levels were identified between control and different inoculum sizes. Functional analysis showed that proteins participating in photosynthesis (light reaction) and Calvin cycle (carbon reaction pathway) had highest expression levels under inoculum size of 1 × 10(6) cells mL(-1), and lowest levels under 1 × 10(7) cells mL(-1). Canonical correlation analysis of the photosynthesis related proteins and metabolites biomarkers showed that a good correlation existed between them (canonical coefficient was 0.987), suggesting photosynthesis process greatly affected microalgae biodiesel productivity and quality. Proteomic study of C. sorokiniana under different illuminations was also conducted to confirm light intensity as a potential limit factor of high inoculum size. Nearly two thirds of proteins showed up-regulation under the illumination of 70-110 µmol m(-2) s(-1), compared to those of 40 µmol m(-2) s(-1). This result suggested that by elegantly adjusting light conditions, high cell density cultivation and high biodiesel production might be achieved. PMID:23096779

Ma, Qian; Wang, Jiangxin; Lu, Shuhuan; Lv, Yajin; Yuan, Yingjin

2013-03-01

268

An indirect enzyme-linked immunosorbent assay for rapid and quantitative assessment of Type III virulence phenotypes of Pseudomonas aeruginosa isolates  

PubMed Central

Background The presence of a Type III secretion system in clinical isolates of Pseudomonas aeruginosa is associated with severe disease and poor outcomes in infections caused by this pathogen. We describe an indirect enzyme-linked immunosorbent assay that rapidly and quantitatively detects two exotoxins, ExoU and ExoT, and two structural components, PopD and PcrV, of the P. aeruginosa Type III secretion system after in-vitro growth in a calcium-free minimal medium. Methods We used this assay to characterize the Type III secretion phenotype of 74 clinical isolates of P. aeruginosa. Findings were compared with results of standard immunoblotting and correlated with Type III secretion-dependent virulence of isolates toward cultured epithelial cells. Results Results of the ELISA assay were concordant with immunoblot detection of the secreted antigens for 73 of 74 isolates. The Type III secretion phenotype assessed by this immunoassay predicted bacterial virulence toward epithelial cells in vitro for all but five of the clinical isolates. Conclusion The availability of an ELISA assay for rapid detection of Type III secreted virulence factors will facilitate large clinical studies to examine whether the Type III secretion phenotype of a P. aeruginosa isolate predicts the course of clinical disease in a patient and should be taken into account in determining optimal treatment strategies for infected patients.

Li, Li; Ledizet, Michel; Kar, Kalipada; Koski, Raymond A; Kazmierczak, Barbara I

2005-01-01

269

Inactivations of rsbU and sarA by IS256 represent novel mechanisms of biofilm phenotypic variation in Staphylococcus epidermidis.  

PubMed

Expression of ica operon-mediated biofilm formation in Staphylococcus epidermidis RP62A is subject to phase variable regulation. Reversible transposition of IS256 into icaADBC or downregulation of icaADBC expression are two important mechanisms of biofilm phenotypic variation. Interestingly, the presence of IS256 was generally associated with a more rapid rate of phenotypic variation, suggesting that IS256 insertions outside the ica locus may affect ica transcription. Consistent with this, we identified variants with diminished ica expression, which were associated with IS256 insertions in the sigmaB activator rsbU or sarA. Biofilm development and ica expression were activated only by ethanol and not NaCl in rsbU::IS256 insertion variants, which were present in approximately 11% of all variants. sigmaB activity was impaired in rsbU::IS256 variants, as evidenced by reduced expression of the sigmaB-regulated genes asp23, csb9, and rsbV. Moreover, expression of sarA, which is sigmaB regulated, and SarA-regulated RNAIII were also suppressed. A biofilm-forming phenotype was restored to rsbU::IS256 variants only after repeated passage and was not associated with IS256 excision from rsbU. Only one sarA::IS256 insertion mutant was identified among 43 biofilm-negative variants. Both NaCl and ethanol-activated ica expression in this sarA::IS256 variant, but only ethanol increased biofilm development. Unlike rsbU::IS256 variants, reversion of the sarA::IS256 variant to a biofilm-positive phenotype was accompanied by precise excision of IS256 from sarA and restoration of normal ica expression. These data identify new roles for IS256 in ica and biofilm phenotypic variation and demonstrate the capacity of this element to influence the global regulation of transcription in S. epidermidis. PMID:15342591

Conlon, Kevin M; Humphreys, Hilary; O'Gara, James P

2004-09-01

270

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

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.

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

271

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

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

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

272

Effect of Genetic Variation in STXBP5 and STX2 on von Willebrand Factor and Bleeding Phenotype in Type 1 von Willebrand Disease Patients  

PubMed Central

Background In type 1 von Willebrand Disease (VWD) patients, von Willebrand Factor (VWF) levels and bleeding symptoms are highly variable. Recently, the association between genetic variations in STXBP5 and STX2 with VWF levels has been discovered in the general population. We assessed the relationship between genetic variations in STXBP5 and STX2, VWF levels, and bleeding phenotype in type 1 VWD patients. Methods In 158 patients diagnosed with type 1 VWD according to the current ISTH guidelines, we genotyped three tagging-SNPs in STXBP5 and STX2 and analyzed their relationship with VWF:Ag levels and the severity of the bleeding phenotype, as assessed by the Tosetto bleeding score. Results In STX2, rs7978987 was significantly associated with VWF:Ag levels (bèta-coefficient (?)?=??0.04 IU/mL per allele, [95%CI ?0.07;?0.001], p?=?0.04) and VWF:CB activity (??=??0.12 IU/mL per allele, [95%CI ?0.17;?0.06], p<0.0001). For rs1039084 in STXBP5 a similar trend with VWF:Ag levels was observed: (??=??0.03 IU/mL per allele [95% CI ?0.06;0.003], p?=?0.07). In women, homozygous carriers of the minor alleles of both SNPs in STXBP5 had a significantly higher bleeding score than homozygous carriers of the major alleles. (Rs1039084 p?=?0.01 and rs9399599 p?=?0.02). Conclusions Genetic variation in STX2 is associated with VWF:Ag levels in patients diagnosed with type 1 VWD. In addition, genetic variation in STXBP5 is associated with bleeding phenotype in female VWD patients. Our findings may partly explain the variable VWF levels and bleeding phenotype in type 1 VWD patients.

van Loon, Janine E.; Sanders, Yvonne V.; de Wee, Eva M.; Kruip, Marieke J. H. A.; de Maat, Moniek P. M.; Leebeek, Frank W. G.

2012-01-01

273

Natural Variation in Neuron Number in Mice Is Linked to a Major Quantitative Trait Locus on Chr 11  

Microsoft Academic Search

d Erbb2--- encodereceptors for retinoic acid, thyroxine, and neuregulin, respectively.Each receptor is expressed in the retina during development,and their ligands affect the proliferation or survival ofretinal cells.Key words: brain evolution; brain weight; composite intervalmapping; gene polymorphism; inner nuclear layer; linkage analysis;mouse chromosome 11; natural variation; neuron number;optic nerve; outer nuclear layer; quantitative trait locus; recombinantinbred strains;...

Robert W. Williams; Richelle C. Strom; Dan Goldowitz

1998-01-01

274

Variation of quantitative composition of phenolic compounds in rowan (Sorbus aucuparia L.) leaves during the growth season.  

PubMed

The aim of our study was to explore variation peculiarities of qualitative and quantitative composition of phenolic compounds in leaf samples of rowan (Sorbus aucuparia L.) plants growing in natural habitats of Lithuania during their growth season using the HPLC method. In rowan leaf samples, collected during different phenological stages, qualitative and quantitative estimation of neochlorogenic acid, chlorogenic acid, caffeic acid, hyperoside, isoquercitrin, rutin, astragalin, ( - )-epicatechin, procyanidin B1 and procyanidin B2 was performed. Analysis of the qualitative and quantitative composition of phenolic compounds in ethanol extracts of leaf samples of S. aucuparia growing in natural habitats of Lithuania revealed a close relationship between the content of phenolic compounds in S. aucuparia raw plant material and different growth stages. PMID:24697599

Gaivelyte, Kristina; Jakstas, Valdas; Razukas, Almantas; Janulis, Valdimaras

2014-07-01

275

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

PubMed Central

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.

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

2010-01-01

276

A single nucleotide polymorphism tags variation in the arylamine N-acetyltransferase 2 phenotype in populations of European background  

PubMed Central

Objective The arylamine N-acetyltransferase 2 (NAT2) slow acetylation phenotype is an established risk factor for urinary bladder cancer. We previously reported on this risk association using NAT2 phenotypic categories inferred from NAT2 haplotypes based on 7 single nucleotide polymorphisms (SNPs) in a study in Spain. In a subsequent genome-wide scan, we have identified a single common tag SNP (rs1495741) located in the 3? end of NAT2 that is also associated with bladder cancer risk. The aim of this report is to evaluate the agreement between the common tag SNP and the 7-SNP NAT2 inferred phenotype. Methods The agreement between the 7-SNP NAT2 inferred phenotype and the tag SNP, rs1495741, was initially assessed in 2,174 subjects from the Spanish Bladder Cancer Study (SBCS), and confirmed in a subset of subjects from the Main and Vermont component the New England Bladder Cancer Study (NEBCS). We also investigated the association of rs1495741 genotypes with NAT2 catalytic activity in cryopreserved hepatocytes from 154 individuals of European background. Results We observed very strong agreement between rs1495741 and the 7-SNP inferred NAT2 phenotype: sensitivity and specificity for the NAT2 slow phenotype was 99% and 95%, respectively. Our findings were replicated in an independent population from the United States. Estimates for the association between NAT2 slow phenotype and bladder cancer risk in the SBCS and its interaction with cigarette smoking were comparable for the 7-SNP inferred NAT2 phenotype and rs1495741. In addition, rs1495741 genotypes were strongly related to NAT2 activity measured in hepatocytes (P<0.0001). Conclusion A novel NAT2 tag SNP (rs1495741) predicts with high accuracy the 7- SNP inferred NAT2 phenotype, and thus can be used as a sole marker in pharmacogenetic or epidemiological studies of populations of European background. These findings illustrate the utility of tag SNPs, often employed in genome-wide association studies (GWAS), to identify novel phenotypic markers. Further studies are required to determine the functional implications of this novel SNP and the structure and evolution of the haplotype on which it resides.

Garcia-Closas, Montserrat; Hein, David W.; Silverman, Debra; Malats, Nuria; Yeager, Meredith; Jacobs, Kevin; Doll, Mark A; Figueroa, Jonine D; Baris, Dalsu; Schwenn, Molly; Kogevinas, Manolis; Johnson, Alison; Chatterjee, Nilanjan; Moore, Lee E.; Moeller, Timothy; Real, Francisco X.; Chanock, Stephen; Rothman, Nathaniel

2010-01-01

277

Temporal Variations of Skin Pigmentation in C57Bl\\/6 Mice Affect Optical Bioluminescence Quantitation  

Microsoft Academic Search

Purpose  Depilation-induced skin pigmentation in C57Bl\\/6 mice is a known occurrence, and presents a unique problem for quantitative\\u000a optical imaging of small animals, especially for bioluminescence. The work reported here quantitatively investigated the optical\\u000a attenuation of bioluminescent light due to melanin pigmentation in the skin of transgenic C57Bl\\/6 mice, modified such that\\u000a luciferase expression is under the transcription control of a

Allison Curtis; Katherine Calabro; Jean-Rene Galarneau; Irving J. Bigio; Thomas Krucker

278

Transforming growth factor-2 is involved in quantitative genetic variation in thymic involution  

Microsoft Academic Search

The mechanisms regulating thymic invo- lution are unclear. In inbred mouse strains the rate of thymic involution and the function of the hematopoietic stem cell (HSC) compartment are subject to quanti- tative genetic variation. We have shown previously that transforming growth fac- tor-2 (TGF-2) is a genetically deter- mined positive regulator of HSCs. Here, we demonstrate that genetic variation in

Ritu Kumar; Jessica C. Langer; Hans-Willem Snoeck

279

A pyramid breeding of eight grain-yield related quantitative trait loci based on marker-assistant and phenotype selection in rice (Oryza sativa L.).  

PubMed

1000-Grain weight and spikelet number per panicle are two important components for rice grain yield. In our previous study, eight quantitative trait loci (QTLs) conferring spikelet number per panicle and 1000-grain weight were mapped through sequencing-based genotyping of 150 rice recombinant inbred lines (RILs). In this study, we validated the effects of four QTLs from Nipponbare using chromosome segment substitution lines (CSSLs), and pyramided eight grain yield related QTLs. The new lines containing the eight QTLs with positive effects showed increased panicle and spikelet size as compared with the parent variety 93-11. We further proposed a novel pyramid breeding scheme based on marker-assistant and phenotype selection (MAPS). This scheme allowed pyramiding of as many as 24 QTLs at a single hybridization without massive cross work. This study provided insights into the molecular basis of rice grain yield for direct wealth for high-yielding rice breeding. PMID:22835980

Zong, Guo; Wang, Ahong; Wang, Lu; Liang, Guohua; Gu, Minghong; Sang, Tao; Han, Bin

2012-07-20

280

Genotype-phenotype mapping in a post-GWAS world  

PubMed Central

Understanding how metabolic reactions, cell signaling, and developmental pathways translate the genome of an organism into its phenotype is a grand challenge in biology. Genome-wide association studies (GWAS) statistically connect genotypes to phenotypes, without any recourse to known molecular interactions, whereas a molecular biology approach directly ties gene function to phenotype through gene regulatory networks (GRNs). Using natural variation in allele-specific expression, GWAS and GRN approaches can be merged into a single framework via structural equation modeling (SEM). This approach leverages the myriad of polymorphisms in natural populations to elucidate and quantitate the molecular pathways that underlie phenotypic variation. The SEM framework can be used to quantitate a GRN, evaluate its consistency across environments or sexes, identify the differences in GRNs between species, and annotate GRNs de novo in non-model organisms.

Nuzhdin, Sergey V.; Friesen, Maren L.; McIntyre, Lauren M.

2012-01-01

281

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.  

PubMed

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation. The maximum pointwise P values, expressed as the negative logarithm (base 10), were found on 1q (3.95), 4q (3.84), 7p (3.90), 12q (4.74), and 13q (3.81). These five loci met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value). QTLs on chromosomes 1, 12, and 13 are likely to be female specific. One locus, on chromosome 1, is syntenic with that reported from QTL mapping of rodent emotionality, an animal model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous. PMID:12612864

Fullerton, Jan; Cubin, Matthew; Tiwari, Hemant; Wang, Chenxi; Bomhra, Amarjit; Davidson, Stuart; Miller, Sue; Fairburn, Christopher; Goodwin, Guy; Neale, Michael C; Fiddy, Simon; Mott, Richard; Allison, David B; Flint, Jonathan

2003-04-01

282

Genetic linkage map of the guppy, Poecilia reticulata, and quantitative trait loci analysis of male size and colour variation  

PubMed Central

We report construction of a genetic linkage map of the guppy genome using 790 single nucleotide polymorphism markers, integrated from six mapping crosses. The markers define 23 linkage groups (LGs), corresponding to the known haploid number of guppy chromosomes. The map, which spans a genetic length of 899?cM, includes 276 markers linked to expressed genes (expressed sequence tag), which have been used to derive broad syntenic relationships of guppy LGs with medaka chromosomes. This combined linkage map should facilitate the advancement of genetic studies for a wide variety of complex adaptive phenotypes relevant to natural and sexual selection in this species. We have used the linkage data to predict quantitative trait loci for a set of variable male traits including size and colour pattern. Contributing loci map to the sex LG for many of these traits.

Tripathi, Namita; Hoffmann, Margarete; Willing, Eva-Maria; Lanz, Christa; Weigel, Detlef; Dreyer, Christine

2009-01-01

283

Quantitative genetic variation for oviposition preference with respect to phenylthiocarbamide in Drosophila melanogaster.  

PubMed

Seven isogenic strains of Drosophila melanogaster were assayed for oviposition preference on food with phenylthiocarbamide (PTC) versus plain food. There was significant variation among strains for the percentage of eggs oviposited on each medium, ranging from 70 +/- 4% (SE) preference for plain food to no significant preference. Reciprocal hybrid, backcross, and F2 generations derived from two extreme parent strains revealed significant additive and nonadditive genetic variation but no evidence of maternal, paternal, or sex-chromosome effects. PMID:10547926

Possidente, B; Mustafa, M; Collins, L

1999-05-01

284

A Novel Quantitative Approach for Eliminating Sample-To-Sample Variation Using a Hue Saturation Value Analysis Program  

PubMed Central

Objectives As computing technology and image analysis techniques have advanced, the practice of histology has grown from a purely qualitative method to one that is highly quantified. Current image analysis software is imprecise and prone to wide variation due to common artifacts and histological limitations. In order to minimize the impact of these artifacts, a more robust method for quantitative image analysis is required. Methods and Results Here we present a novel image analysis software, based on the hue saturation value color space, to be applied to a wide variety of histological stains and tissue types. By using hue, saturation, and value variables instead of the more common red, green, and blue variables, our software offers some distinct advantages over other commercially available programs. We tested the program by analyzing several common histological stains, performed on tissue sections that ranged from 4 µm to 10 µm in thickness, using both a red green blue color space and a hue saturation value color space. Conclusion We demonstrated that our new software is a simple method for quantitative analysis of histological sections, which is highly robust to variations in section thickness, sectioning artifacts, and stain quality, eliminating sample-to-sample variation.

McMullen, Eri; Figueiredo, Jose Luiz; Aikawa, Masanori; Aikawa, Elena

2014-01-01

285

Association of an insulin-like growth factor 1 gene microsatellite with phenotypic variation and estimated breeding values of growth traits in Canchim cattle.  

PubMed

A population of 1398 Canchim (CA) cattle was genotyped to assess the association of an insulin-like growth factor 1 (IGF1) gene microsatellite with phenotypic variation and estimated breeding values of pre-weaning, weaning and post-weaning growth traits. After an initial analysis, the IGF1 genotype only had a significant effect (P < 0.05) on birth weight (BW) and weaning weight adjusted to 240 days (WW240). For these two traits, direct and maternal breeding values were estimated using the restricted maximum likelihood (reml). Two analyses were carried out. In the first (Model I), all fixed effects were fitted. In the second (Model II), the fixed effect of the IGF1 genotype was omitted. The estimated genetic and phenotypic components of variance were similar for every trait in both models. For Model I, estimated direct and maternal heritabilities were 0.26 and 0.16 for BW and 0.23 and 0.14 for WW240 respectively. The genetic and phenotypic correlations between BW and WW240 were 0.38 and 0.38 (Model I) and 0.19 and 0.38 (Model II) respectively. Fifty animals were classified according to their direct and maternal breeding values for both traits. Spearman rank-order correlation between animal rankings in the two models was used to assess the effect of including the IGF1 genotype in the model. Non-significant values from this correlation were indicative of a difference in breeding value rankings between the two approaches. The IGF1 gene was found to be associated with phenotypic variation and breeding values in the early phase of growth. PMID:18637878

Andrade, P C; Grossi, D A; Paz, C C P; Alencar, M M; Regitano, L C A; Munari, D P

2008-10-01

286

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

PubMed

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

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

2004-01-01

287

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

Microsoft Academic Search

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

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

1997-01-01

288

Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster  

Microsoft Academic Search

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

Thomas L. Turner; Andrew D. Stewart; Andrew T. Fields; William R. Rice; Aaron M. Tarone

2011-01-01

289

3D Geometry and Quantitative Variation of the Cervico-Thoracic Region in Crocodylia.  

PubMed

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. Anat Rec, 297:1278-1291, 2014. © 2014 Wiley Periodicals, Inc. PMID:24753482

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

2014-07-01

290

A Semi-Quantitative Method to Denote Generic Physical Activity Phenotypes from Long-Term Accelerometer Data - The ATLAS Index  

PubMed Central

Background Physical activity is inversely correlated to morbidity and mortality risk. Large cohort studies use wearable accelerometer devices to measure physical activity objectively, providing data potentially relevant to identify different activity patterns and to correlate these to health-related outcome measures. A method to compute relevant characteristics of such data not only with regard to duration and intensity, but also to regularity of activity events, is necessary. The aims of this paper are to propose a new method – the ATLAS index (Activity Types from Long-term Accelerometric Sensor data) – to derive generic measures for distinguishing different characteristic activity phenotypes from accelerometer data, to propose a comprehensive graphical representation, and to conduct a proof-of-concept with long-term measurements from different devices and cohorts. Methods The ATLAS index consists of the three dimensions regularity (reg), duration (dur) and intensity (int) of relevant activity events identified in long-term accelerometer data. It can be regarded as a 3D vector and represented in a 3D cube graph. 12 exemplary data sets of three different cohort studies with 99,467 minutes of data were chosen for concept validation. Results Five archetypical activity types are proposed along with their dimensional characteristics (insufficiently active: low reg, int and dur; busy bee: low dur and int, high reg; cardio-active: medium reg, int and dur, endurance athlete: high reg, int and dur; and weekend warrior: high int and dur, low reg). The data sets are displayed in one common graph, indicating characteristic differences in activity patterns. Conclusion The ATLAS index incorporates the relevant regularity dimension apart from the widely-used measures of duration and intensity. Along with the 3D representation, it allows to compare different activity types in cohort study populations, both visually and computationally using vector distance measures. Further research is necessary to validate the ATLAS index in order to find normative values and group centroids.

Marschollek, Michael

2013-01-01

291

Quantitative genetic variation of enzyme activities in natural populations of Drosophila melanogaster  

PubMed Central

The genetic component of variation of enzyme activity in natural populations of Drosophila melanogaster was investigated by using two sets of chromosome substitution lines. The constitution of a line of each type is: i1/i1;+2/ +2;i3/i3 and i1/i1;i2/ i2;+3/+3, where i refers to a chromosome from a highly inbred line and + refers to a chromosome from a natural population. The + but not the i chromosomes vary within a set of lines. By use of a randomized block design to test and estimate components of variance, 50 of the second- and 50 of the third- chromosome substitution lines have been screened for variation in the activity levels of seven enzymes. Six of the seven enzymes show a significant genetic component in at least one set of lines, and five of the seven enzymes show activity variations attributable to factors that are not linked to the structural gene. These unlinked activity modifiers identify possible regulatory elements. Analyses of covariance show that most of the genetic variation of enzyme activities cannot be accounted for by genetic variation of live weight or protein content. These results and the lack of strong correlations between the genetic effects on the activities of different enzymes indicate that the effects are mainly specific for individual enzymes.

Laurie-Ahlberg, C. C.; Maroni, G.; Bewley, G. C.; Lucchesi, J. C.; Weir, B. S.

1980-01-01

292

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

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

293

Complex genetics controls natural variation among seed quality phenotypes in a recombinant inbred population of an interspecific cross between Solanum lycopersicum × Solanum pimpinellifolium.  

PubMed

Seed quality in tomato is associated with many complex physiological and genetic traits. While plant processes are frequently controlled by the action of small- to large-effect genes that follow classic Mendelian inheritance, our study suggests that seed quality is primarily quantitative and genetically complex. Using a recombinant inbred line population of Solanum lycopersicum?×?Solanum pimpinellifolium, we identified quantitative trait loci (QTLs) influencing seed quality phenotypes under non-stress, as well as salt, osmotic, cold, high-temperature and oxidative stress conditions. In total, 42 seed quality traits were analysed and 120 QTLs were identified for germination traits under different conditions. Significant phenotypic correlations were observed between germination traits under optimal conditions, as well as under different stress conditions. In conclusion, one or more QTLs were identified for each trait with some of these QTLs co-locating. Co-location of QTLs for different traits can be an indication that a locus has pleiotropic effects on multiple traits due to a common mechanistic basis. However, several QTLs also dissected seed quality in its separate components, suggesting different physiological mechanisms and signalling pathways for different seed quality attributes. PMID:22074055

Kazmi, Rashid H; Khan, Noorullah; Willems, Leo A J; VAN Heusden, Adriaan W; Ligterink, Wilco; Hilhorst, Henk W M

2012-05-01

294

Quantitative correlation between the local coercivity variation and magnetization reversal dynamics in Co/Pd multilayer thin films  

NASA Astrophysics Data System (ADS)

We report the existence of a quantitative correlation between magnetization reversal dynamics and spatial variation of the local coercivity, ?HC, in Co/Pd multilayer thin films. The ?HC was directly probed by measuring hysteresis loops on spatially resolved local regions by means of a magneto-optical microscope magnetometer and magnetization reversal dynamics was characterized by analyzing the wall-motion speed V and the nucleation rate R. We found a linear relationship between log(V/R) and log(?HC), where a small variation of the local coercivity results in a large V/R showing wall-motion dominant reversal behavior. A Monte Carlo simulation considering magnetic nonuniformity well predicts the observed experimental relationship.

Jang, Hyuk-Jae; Choe, Sug-Bong; Shin, Sung-Chul

2003-06-01

295

GENETIC CONTROL OF QUANTITATIVE VARIATION IN SELF-INCOMPATIBILITY PROTEINS DETECTED BY IMMUNODIFFUSION1  

Microsoft Academic Search

Single radial immunodiffusion was used to study the self-incompatibility (S) proteins present in stigmas of two inbred lines of Brassica oleracea: a self- incompatible line and a self-compatible mutant derived from it. The genetic basis of observed quantitative differences in S proteins between the two inbreds was shown to be determined by a single gene with dosage effects. Self-pdli- nation

M. E. NASRALLAH

296

The contribution of dominance to the understanding of quantitative genetic variation.  

PubMed

SummaryKnowledge of the genetic architecture of a quantitative trait is useful to adjust methods for the prediction of genomic breeding values and to discover the extent to which common assumptions in quantitative trait locus (QTL) mapping experiments and breeding value estimation are violated. It also affects our ability to predict the long-term response of selection. In this paper, we focus on additive and dominance effects of QTL. We derive formulae that can be used to estimate the number of QTLs that affect a quantitative trait and parameters of the distribution of their additive and dominance effects from variance components, inbreeding depression and results from QTL mapping experiments. It is shown that a lower bound for the number of QTLs depends on the ratio of squared inbreeding depression to dominance variance. That is, high inbreeding depression must be due to a sufficient number of QTLs because otherwise the dominance variance would exceed the true value. Moreover, the second moment of the dominance coefficient depends only on the ratio of dominance variance to additive variance and on the dependency between additive effects and dominance coefficients. This has implications on the relative frequency of overdominant alleles. It is also demonstrated how the expected number of large QTLs determines the shape of the distribution of additive effects. The formulae are applied to milk yield and productive life in Holstein cattle. Possible sources for a potential bias of the results are discussed. PMID:21481291

Wellmann, Robin; Bennewitz, Jörn

2011-04-01

297

The impact of intraspecific variation in a fish predator on the evolution of phenotypic plasticity and investment in sex in Daphnia ambigua.  

PubMed

Theory predicts that the evolution of phenotypic plasticity depends upon cues that indicate environmental change. Predators typically induce plastic responses in prey. However, variation among populations of predators alters the frequency of predation and, possibly, the evolution of plasticity. We compared responses to predator cues in Daphnia ambigua from lakes where alewife (Alosa pseudoharengus) either do (anadromous) or do not (landlocked) migrate between marine and freshwater. In 'anadromous' lakes, Daphnia are abundant each spring but eliminated by alewives in summer, whereas Daphnia are constantly under the threat of predation in 'landlocked' lakes. Daphnia from 'anadromous' lakes grew faster, matured earlier and larger, produced more offspring and invested more in sex than Daphnia from landlocked lakes. We observed several significant lake type-by-predator treatment interactions. These interactions, whereby the differences between lakes were greater in predator-conditioned water, agree with theory and argue that Daphnia plasticity has been influenced by variation in alewives. PMID:22022990

Walsh, Matthew R; Post, D M

2012-01-01

298

Quantitative variation in maize kernel row number is controlled by the FASCIATED EAR2 locus.  

PubMed

Domestication of cereal crops, such as maize, wheat and rice, had a profound influence on agriculture and the establishment of human civilizations. One major improvement was an increase in seed number per inflorescence, which enhanced yield and simplified harvesting and storage. The ancestor of maize, teosinte, makes 2 rows of kernels, and modern varieties make ?8-20 rows. Kernel rows are initiated by the inflorescence shoot meristem, and shoot meristem size is controlled by a feedback loop involving the CLAVATA signaling proteins and the WUSCHEL transcription factor. We present a hypothesis that variation in inflorescence meristem size affects kernel row number (KRN), with the potential to increase yield. We also show that variation in the CLAVATA receptor-like protein FASCIATED EAR2 leads to increased inflorescence meristem size and KRN. These findings indicate that modulation of fundamental stem cell proliferation control pathways has the potential to enhance crop yields. PMID:23377180

Bommert, Peter; Nagasawa, Namiko Satoh; Jackson, David

2013-03-01

299

Quantitative genetic variation in populations of Amsinckia spectabilis that differ in rate of self-fertilization.  

PubMed

Self-fertilization is expected to reduce genetic diversity within populations and consequently to limit adaptability to changing environments. Little is known, however, about the way the evolution of self-fertilization changes the amount or pattern of the components of genetic variation in natural populations. In this study, a reciprocal North Carolina II design and maximum-likelihood methods were implemented to investigate the genetic basis of variation for 15 floral and vegetative traits in four populations of the annual plant Amsinckia spectabilis (Boraginaceae) differing in mating system. Six variance components were estimated according to Cockerham and Weir's "bio" model c. Compared to the three partially selfing populations, we found significantly lower levels of nuclear variance for several traits in the nearly completely self-fertilizing population. Furthermore, for 11 of 15 traits we did not detect nuclear variation to be significantly greater than zero. We also found high maternal variance in one of the partially selfing populations for several traits, and little dominance variance in any population. These results are in agreement with the evolutionary dead-end hypothesis for highly self-fertilizing taxa. PMID:19236472

Bartkowska, Magdalena P; Johnston, Mark O

2009-05-01

300

The Contribution of RNA Decay Quantitative Trait Loci to Inter-Individual Variation in Steady-State Gene Expression Levels  

PubMed Central

Recent gene expression QTL (eQTL) mapping studies have provided considerable insight into the genetic basis for inter-individual regulatory variation. However, a limitation of all eQTL studies to date, which have used measurements of steady-state gene expression levels, is the inability to directly distinguish between variation in transcription and decay rates. To address this gap, we performed a genome-wide study of variation in gene-specific mRNA decay rates across individuals. Using a time-course study design, we estimated mRNA decay rates for over 16,000 genes in 70 Yoruban HapMap lymphoblastoid cell lines (LCLs), for which extensive genotyping data are available. Considering mRNA decay rates across genes, we found that: (i) as expected, highly expressed genes are generally associated with lower mRNA decay rates, (ii) genes with rapid mRNA decay rates are enriched with putative binding sites for miRNA and RNA binding proteins, and (iii) genes with similar functional roles tend to exhibit correlated rates of mRNA decay. Focusing on variation in mRNA decay across individuals, we estimate that steady-state expression levels are significantly correlated with variation in decay rates in 10% of genes. Somewhat counter-intuitively, for about half of these genes, higher expression is associated with faster decay rates, possibly due to a coupling of mRNA decay with transcriptional processes in genes involved in rapid cellular responses. Finally, we used these data to map genetic variation that is specifically associated with variation in mRNA decay rates across individuals. We found 195 such loci, which we named RNA decay quantitative trait loci (“rdQTLs”). All the observed rdQTLs are located near the regulated genes and therefore are assumed to act in cis. By analyzing our data within the context of known steady-state eQTLs, we estimate that a substantial fraction of eQTLs are associated with inter-individual variation in mRNA decay rates.

Pai, Athma A.; Cain, Carolyn E.; Mizrahi-Man, Orna; De Leon, Sherryl; Lewellen, Noah; Veyrieras, Jean-Baptiste; Degner, Jacob F.; Gaffney, Daniel J.; Pickrell, Joseph K.; Stephens, Matthew; Pritchard, Jonathan K.; Gilad, Yoav

2012-01-01

301

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

PubMed Central

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.

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

2013-01-01

302

Variation in Psychosis Gene ZNF804A Is Associated With a Refined Schizotypy Phenotype but Not Neurocognitive Performance in a Large Young Male Population  

PubMed Central

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.

Stefanis, Nicholas C.

2013-01-01

303

Identification of Quantitative Trait Loci Affecting Murine Long Bone Length in a Two-Generation Intercross of LG\\/J and SM\\/J Mice  

Microsoft Academic Search

Introduction: Study of mutations with large phenotypic effects has allowed the identification of key players in skeletal development. However, the molecular nature of variation in large, phenotypically normal populations tends to be characterized by smaller phenotypic effects that remain undefined. Materials and Methods: We use interval mapping and quantitative trait locus (QTL) mapping techniques in the combined F2-F3 populations (n

Elizabeth A Norgard; Charles C Roseman; Gloria L Fawcett; Mihaela Pavlicev; Clinton D Morgan; L Susan Pletscher; Bing Wang; James M Cheverud

2008-01-01

304

Effects of bottlenecks on quantitative genetic variation in the butterfly Bicyclus anynana.  

PubMed

The effects of a single population bottleneck of differing severity on heritability and additive genetic variance was investigated experimentally using a butterfly. An outbred laboratory stock was used to found replicate lines with one pair, three pairs and 10 pairs of adults, as well as control lines with approximately 75 effective pairs. Heritability and additive genetic variance of eight wing pattern characters and wing size were estimated using parent-offspring covariances in the base population and in all daughter lines. Individual morphological characters and principal components of the nine characters showed a consistent pattern of treatment effects in which average heritability and additive genetic variance was lower in one pair and three pair lines than in 10 pair and control lines. Observed losses in heritability and additive genetic variance were significantly greater than predicted by the neutral additive model when calculated with coefficients of inbreeding estimated from demographic parameters alone. However, use of molecular markers revealed substantially more inbreeding, generated by increased variance in family size and background selection. Conservative interpretation of a statistical analysis incorporating this previously undetected inbreeding led to the conclusion that the response to inbreeding of the morphological traits studied showed no significant departure from the neutral additive model. This result is consistent with the evidence for minimal directional dominance for these traits. In contrast, egg hatching rate in the same experimental lines showed strong inbreeding depression, increased phenotypic variance and rapid response to selection, highly indicative of an increase in additive genetic variance due to dominance variance conversion. PMID:11355572

Saccheri, I J; Nichols, R A; Brakefield, P M

2001-04-01

305

The cost of keeping eggs fresh: quantitative genetic variation in females that mate late relative to sexual maturation.  

PubMed

In many species, females abandon mate choice to ensure that eggs are fertilized before they are lost. But why do females not just maintain oocytes longer if there is a benefit to mate choice? We conducted a quantitative genetic study in the cockroach Nauphoeta cinerea to test whether genetic constraints prevent the evolution of oocyte maintenance or selection against oocyte loss is weak when females mate late relative to sexual maturity. We found standing genetic variation within the population and no evidence for genetic constraints. Levels of genetic variation are of the magnitude found for life-history traits in general, suggesting that this trait has been exposed to selection. We unexpectedly found two categories of females: those that delay reproduction and those that reproduce at a normal time when mating late, which could indicate alternative strategies. However, frequency-dependent selection does not maintain this variation as females that delay always reproduce less well. Given these findings, we suggest that there may be advantages to egg degradation. The evolution of maintenance of fertilizable oocytes over time would then be constrained by the need to maintain the mechanism by which females control the distribution of resources between current and future reproductive events. PMID:17243076

Moore, Patricia J; Harris, W Edwin; Moore, Allen J

2007-03-01

306

Rapid and Inexpensive Screening of Genomic Copy Number Variations Using a Novel Quantitative Fluorescent PCR Method  

PubMed Central

Detection of human microdeletion and microduplication syndromes poses significant burden on public healthcare systems in developing countries. With genome-wide diagnostic assays frequently inaccessible, targeted low-cost PCR-based approaches are preferred. However, their reproducibility depends on equally efficient amplification using a number of target and control primers. To address this, the recently described technique called Microdeletion/Microduplication Quantitative Fluorescent PCR (MQF-PCR) was shown to reliably detect four human syndromes by quantifying DNA amplification in an internally controlled PCR reaction. Here, we confirm its utility in the detection of eight human microdeletion syndromes, including the more common WAGR, Smith-Magenis, and Potocki-Lupski syndromes with 100% sensitivity and 100% specificity. We present selection, design, and performance evaluation of detection primers using variety of approaches. We conclude that MQF-PCR is an easily adaptable method for detection of human pathological chromosomal aberrations.

Han, Joan C.; Elsea, Sarah H.; Pena, Heloisa B.; Pena, Sergio Danilo Junho

2013-01-01

307

Rapid and inexpensive screening of genomic copy number variations using a novel quantitative fluorescent PCR method.  

PubMed

Detection of human microdeletion and microduplication syndromes poses significant burden on public healthcare systems in developing countries. With genome-wide diagnostic assays frequently inaccessible, targeted low-cost PCR-based approaches are preferred. However, their reproducibility depends on equally efficient amplification using a number of target and control primers. To address this, the recently described technique called Microdeletion/Microduplication Quantitative Fluorescent PCR (MQF-PCR) was shown to reliably detect four human syndromes by quantifying DNA amplification in an internally controlled PCR reaction. Here, we confirm its utility in the detection of eight human microdeletion syndromes, including the more common WAGR, Smith-Magenis, and Potocki-Lupski syndromes with 100% sensitivity and 100% specificity. We present selection, design, and performance evaluation of detection primers using variety of approaches. We conclude that MQF-PCR is an easily adaptable method for detection of human pathological chromosomal aberrations. PMID:24288428

Stofanko, Martin; Han, Joan C; Elsea, Sarah H; Pena, Heloísa B; Gonçalves-Dornelas, Higgor; Pena, Sérgio Danilo Junho

2013-01-01

308

Quantitative Analysis of Competition in Posttranscriptional Regulation Reveals a Novel Signature in Target Expression Variation  

PubMed Central

When small RNAs are loaded onto Argonaute proteins they can form the RNA-induced silencing complexes (RISCs), which mediate RNA interference (RNAi). RISC-formation is dependent on a shared pool of Argonaute proteins and RISC-loading factors, and is susceptible to competition among small RNAs. We present a mathematical model that aims to understand how small RNA competition for RISC-formation affects target gene repression. We discuss that small RNA activity is limited by RISC-formation, RISC-degradation, and the availability of Argonautes. We show that different competition conditions for RISC-loading result in different signatures of RNAi determined also by the amount of RISC-recycling taking place. In particular, we find that the small RNAs, although less efficient at RISC-formation, can perform in the low RISC-recycling range as well as their more effective counterparts. Additionally, we predict that under conditions of low RISC-loading efficiency and high RISC-recycling, the variation in target levels increases linearly with the target transcription rate. Furthermore, we show that RISC-recycling determines the effect that Argonaute scarcity conditions have on target expression variation. Our observations, taken together, offer a framework of predictions that can be used to infer from data the particular characteristics of underlying RNAi activity.

Klironomos, Filippos D.; Berg, Johannes

2013-01-01

309

Exploring patterns of interspecific variation in quantitative traits using sequential phylogenetic eigenvector regressions.  

PubMed

A number of metrics have been developed for estimating phylogenetic signal in data and to evaluate correlated evolution, inferring broad-scale evolutionary and ecological processes. Here, we proposed an approach called phylogenetic signal-representation (PSR) curve, built upon phylogenetic eigenvector regression (PVR). In PVR, selected eigenvectors extracted from a phylogenetic distance matrix are used to model interspecific variation. In the PSR curve, sequential PVR models are fitted after successively increasing the number of eigenvectors and plotting their R(2) against the accumulated eigenvalues. We used simulations to show that a linear PSR curve is expected under Brownian motion and that its shape changes under alternative evolutionary models. The PSR area, expressing deviations from Brownian motion, is strongly correlated (r= 0.873; P < 0.01) with Blomberg's K-statistics, so nonlinear PSR curves reveal if traits are evolving at a slower or higher rate than expected by Brownian motion. The PSR area is also correlated with phylogenetic half-life under an Ornstein-Uhlenbeck process, suggesting how both methods describe the shape of the relationship between interspecific variation and time since divergence among species. The PSR curve provides an elegant exploratory method to understand deviations from Brownian motion, in terms of acceleration or deceleration of evolutionary rates occurring at large or small phylogenetic distances. PMID:22486690

Diniz Filho, José Alexandre Felizola; Rangel, Thiago F; Santos, Thiago; Bini, Luis Mauricio

2012-04-01

310

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

PubMed

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

Talluto, Matthew V; Benkman, Craig W

2014-07-01

311

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

PubMed Central

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.

Remond, 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

312

Pleiotropic Quantitative Trait Loci Contribute to Population Divergence in Traits Associated With Life-History Variation in Mimulus guttatus  

PubMed Central

Evolutionary biologists seek to understand the genetic basis for multivariate phenotypic divergence. We constructed an F2 mapping population (N = 539) between two distinct populations of Mimulus guttatus. We measured 20 floral, vegetative, and life-history characters on parents and F1 and F2 hybrids in a common garden experiment. We employed multitrait composite interval mapping to determine the number, effect, and degree of pleiotropy in quantitative trait loci (QTL) affecting divergence in floral, vegetative, and life-history characters. We detected 16 QTL affecting floral traits; 7 affecting vegetative traits; and 5 affecting selected floral, vegetative, and life-history traits. Floral and vegetative traits are clearly polygenic. We detected a few major QTL, with all remaining QTL of small effect. Most detected QTL are pleiotropic, implying that the evolutionary shift between these annual and perennial populations is constrained. We also compared the genetic architecture controlling floral trait divergence both within (our intraspecific study) and between species, on the basis of a previously published analysis of M. guttatus and M. nasutus. Eleven of our 16 floral QTL map to approximately the same location in the interspecific map based on shared, collinear markers, implying that there may be a shared genetic basis for floral divergence within and among species of Mimulus.

Hall, Megan C.; Basten, Christopher J.; Willis, John H.

2006-01-01

313

Simple Absolute Quantification Method Correcting for Quantitative PCR Efficiency Variations for Microbial Community Samples  

PubMed Central

Real-time quantitative PCR (qPCR) is a widely used technique in microbial community analysis, allowing the quantification of the number of target genes in a community sample. Currently, the standard-curve (SC) method of absolute quantification is widely employed for these kinds of analysis. However, the SC method assumes that the amplification efficiency (E) is the same for both the standard and the sample target template. We analyzed 19 bacterial strains and nine environmental samples in qPCR assays, targeting the nifH and 16S rRNA genes. The E values of the qPCRs differed significantly, depending on the template. This has major implications for the quantification. If the sample and standard differ in their E values, quantification errors of up to orders of magnitude are possible. To address this problem, we propose and test the one-point calibration (OPC) method for absolute quantification. The OPC method corrects for differences in E and was derived from the ??CT method with correction for E, which is commonly used for relative quantification in gene expression studies. The SC and OPC methods were compared by quantifying artificial template mixtures from Geobacter sulfurreducens (DSM 12127) and Nostoc commune (Culture Collection of Algae and Protozoa [CCAP] 1453/33), which differ in their E values. While the SC method deviated from the expected nifH gene copy number by 3- to 5-fold, the OPC method quantified the template mixtures with high accuracy. Moreover, analyzing environmental samples, we show that even small differences in E between the standard and the sample can cause significant differences between the copy numbers calculated by the SC and the OPC methods.

Bodenhausen, Natacha; Zeyer, Josef; Burgmann, Helmut

2012-01-01

314

Genetic variation in leaf pigment, optical and photosynthetic function among diverse phenotypes of Metrosideros polymorpha grown in a common garden  

Microsoft Academic Search

Coordinated variation has been reported for leaf structure, composition and function, across and within species, and theoretically\\u000a should occur across populations of a species that span an extensive environmental range. We focused on Hawaiian keystone tree\\u000a species Metrosideros polymorpha, specifically, 13-year old trees grown (2–4 m tall) in a common garden (approximately 1 ha field with 2–3 m between trees)\\u000a from seeds collected

Roberta E. Martin; Gregory P. Asner; Lawren Sack

2007-01-01

315

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

PubMed Central

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.

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

2012-01-01

316

Genome-Wide Linkage Scan for Quantitative Trait Loci Underlying Normal Variation in Heel Bone Ultrasound Measures  

PubMed Central

Quantitative ultrasound (QUS) traits are correlated with bone mineral density (BMD), but predict risk for future fracture independent of BMD. Only a few studies, however, have sought to identify specific genes influencing calcaneal QUS measures. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing normal variation in QUS traits. QUS measures were collected from a total of 719 individuals (336 males and 383 females) from the Fels Longitudinal Study who have been genotyped and have at least one set of QUS measurements. Participants ranged in age from 18.0 to 96.6 years and were distributed across 110 nuclear and extended families. Using the Sahara ® bone sonometer, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI) were collected from the right heel. Variance components based linkage analysis was performed on the three traits using 400 polymorphic short tandem repeat (STR) markers spaced approximately 10 cM apart across the autosomes to identify QTL influencing the QUS traits. Age, sex, and other significant covariates were simultaneously adjusted. Heritability estimates (h2) for the QUS traits ranged from 0.42 to 0.57. Significant evidence for a QTL influencing BUA was found on chromosome 11p15 near marker D11S902 (LOD = 3.11). Our results provide additional evidence for a QTL on chromosome 11p that harbors a potential candidate gene(s) related to BUA and bone metabolism.

Lee, M.; Choh, A.C.; Williams, K.D.; Schroeder, V.; Dyer, T.D.; Blangero, J.; Cole, S.A.; Chumlea, WM.C.; Duren, D.L.; Sherwood, R.J.; Siervogel, R.M.; Towne, B.; Czerwinski, S.A.

2012-01-01

317

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

PubMed Central

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.

2013-01-01

318

Mitochondrial control region and protein coding genes sequence variation among phenotypic forms of brown trout Salmo trutta from northern Italy.  

PubMed

The Pô River basin of northern Italy is the home of distinctive and endemic morphological forms of brown trout Salmo trutta. We used PCR-direct sequencing and RFLP techniques to study variation in the mitochondrial control region of 225 trout in order to assess genetic relatedness among 18 populations from that region. The distribution analysis of these genotypes among north Italian populations confirmed the phylogenetic differentiation of marbled trout Salmo trutta marmoratus populations and the postglacial origin of S. t. carpio. Extensive genetic heterogeneity was observed among morphologically identical S. t. fario populations. Introgression with domestic strains of Atlantic basin origin was detected in all forms. In order to assess the phylogenetic congruence detected in coding and noncoding regions of the mitochondrial genome, we also analysed sequence variation in segments of the cytochrome b and ATPase subunit VI genes among representatives of all variants detected in the analysis of the control region. Variation in protein coding genes was only slightly less than that observed in the control region of the same individuals, both in terms of number of variants detected and of pairwise sequence divergence estimates among variants. Phylogenetic analysis based on protein coding genes sequences identified the same phylogenetic groupings defined by the control region analysis and also allowed a partial resolution of their phyletic relationships that was previously unresolved. However, coding and noncoding segments differed substantially in the transition-transversion ratio (17:0 in coding segments vs. 17:6 in control region segments). PMID:7912616

Giuffra, E; Bernatchez, L; Guyomard, R

1994-04-01

319

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

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.

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

1992-01-01

320

The effect of variation in physical properties of porous bioactive glass on the expression and maintenance of the osteoblastic phenotype  

NASA Astrophysics Data System (ADS)

Revision surgery to replace failed hip implants is a significant health care issue that is expected to escalate as life expectancy increases. A major goal of revision surgery is to reconstruct femoral intramedullary bone-stock loss. To address this problem of bone loss, grafting techniques are widely used. Although fresh autografts remain the optimal material for all forms of surgery seeking to restore structural integrity to the skeleton, it is evident that the supply of such tissue is limited. In recent years, calcium phosphate ceramics have been studied as alternatives to autografts and allografts. The significant limitations associated with the use of biological and synthetic grafts have led to a growing interest in the in vitro synthesis of bone tissue. The approach is to synthesize bone tissue in vitro with the patient's own cells, and use this tissue for the repair of bony defects. Various substrates including metals, polymers, calcium phosphate ceramics and bioactive glasses, have been seeded with osteogenic cells. The selection of bioactive glass in this study is based on the fact that this material has shown an intense beneficial biological effect which has not been reproduced by other biomaterials. Even though the literature provides extensive data on the effect of pore size and porosity on in vivo bone tissue ingrowth into porous materials for joint prosthesis fixation, the data from past studies cannot be applied to the use of bioactive glass as a substrate for the in vitro synthesis of bone tissue. First, unlike the in vivo studies in the literature, this research deals with the growth of bone tissue in vitro. Second, unlike the implants used in past studies, bioactive glass is a degradable and resorbable material. Thus, in order to establish optimal substrate characteristics (porosity and pore size) for bioactive glass, it was important to study these parameters in an in vitro model. We synthesized porous bioactive glass substrates (BG) with varying pore sizes and porosity and determined the effect of substrate properties on the expression and maintenance of the osteoblastic phenotype, using an in vitro culture of osteoblast-like cells. Our data showed that porous bioactive glass substrates support the proliferation and maturation of osteoblast-like cells. Within the conditions of the experiment, we also found that at a given porosity of 44% the pore size of bioactive glass neither directs nor modulates the in vitro expression of the osteoblastic phenotype. On the other hand, at an average pore size of 92 mum, when cultures are maintained for 14 days, cell activity is greatly affected by the substrate porosity. As the porosity increases from 35% to 59%, osteoblast activity is adversely affected. (Abstract shortened by UMI.)

Effah Kaufmann, Elsie Akosua Biraa

321

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

PubMed Central

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.

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

2011-01-01

322

Cranial ontogeny in Stegoceras validum (Dinosauria: Pachycephalosauria): a quantitative model of pachycephalosaur dome growth and variation.  

PubMed

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

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

2011-01-01

323

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

SciTech Connect

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.

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

2011-01-01

324

Changes in disease resistance phenotypes associated with plant physiological age are not caused by variation in R gene transcript abundance.  

PubMed

Foliar late blight is one of the most important diseases of potato. Foliar blight resistance has been shown to change as a plant ages. In other pathosystems, resistance (R) gene transcript levels appear to be correlated to disease resistance. The cloning of the broad-spectrum, foliar blight resistance gene RB provided the opportunity to explore how foliar blight resistance and R-gene transcript levels vary with plant age. Plants of Solanum bulbocastanum PT29, from which RB, including the native promoter and other flanking regions, was cloned, and S. tuberosum cv. Dark Red Norland (nontransformed and RB-transformed) representing three different developmental stages were screened for resistance to late blight and RB transcript levels. Preflowering plants of all genotypes exhibited the highest levels of resistance, followed by postflowering and near-senescing plants. The RB transgene significantly affected resistance, enhancing resistance levels of all RB-containing lines, especially in younger plants. RB transgene transcripts were detected at all plant ages, despite weak correlation with disease resistance. Consistent transcript levels in plants of different physiological ages with variable levels of disease resistance demonstrate that changes in disease-resistance phenotypes associated with plant age cannot be attributed to changes in R-gene transcript abundance. PMID:19245330

Millett, Benjamin P; Mollov, Dimitre S; Iorizzo, Massimo; Carputo, Domenico; Bradeen, James M

2009-03-01

325

A comprehensive genotype-phenotype interaction of different Toll-like receptor variations in a renal transplant cohort.  

PubMed

To date, the impact of the TLR (Toll-like receptor) system on early and late kidney transplantation outcome, such as ARE (acute rejection episodes) or cardiovascular morbidity and mortality, has still not been elucidated conclusively. Genetically determined alterations in TLR expression exhibit a possibility to evaluate their role in transplantation. In the present study, we sought to determine a comprehensive genotype-phenotype association with early and late allograft outcomes. We studied 11 SNPs (single nucleotide polymorphisms) in TLR2, TLR3, TLR4, TLR5, TLR9 and within a co-molecule CD14 in 265 patients receiving their first kidney transplant and the association of these with the occurrence of DGF (delayed graft function), ARE or MACE (major adverse cardiovascular events). ARE were significantly more frequent in patients carrying the TLR3 TT/CT allele (43.8 compared with 25.8%; P=0.001) as were rates of DGF (21.4 compared with 12.0%; P=0.030). Furthermore, TLR9 was significantly involved in the occurrence of MACE (TLR9 -1237; P=0.030). Interestingly, there was no significant effect of any TLR polymorphism on graft survival or renal function and the incidence of any infection, including CMV (cytomegalovirus) infection. In conclusion, our present study in renal transplant recipients suggests that the TLR system may be involved in both acute rejection and MACE. Modulation of the TLR system may be a promising target in future therapeutic strategies. PMID:20604744

Krüger, Bernd; Banas, Miriam C; Walberer, Andreas; Böger, Carsten A; Farkas, Stefan; Hoffmann, Ute; Fischereder, Michael; Banas, Bernhard; Krämer, Bernhard K

2010-12-01

326

Joint effects of pleiotropic selection and stabilizing selection on the maintenance of quantitative genetic variation at mutation-selection balance.  

PubMed

In quantitative genetics, there are two basic "conflicting" observations: abundant polygenic variation and strong stabilizing selection that should rapidly deplete that variation. This conflict, although having attracted much theoretical attention, still stands open. Two classes of model have been proposed: real stabilizing selection directly on the metric trait under study and apparent stabilizing selection caused solely by the deleterious pleiotropic side effects of mutations on fitness. Here these models are combined and the total stabilizing selection observed is assumed to derive simultaneously through these two different mechanisms. Mutations have effects on a metric trait and on fitness, and both effects vary continuously. The genetic variance (V(G)) and the observed strength of total stabilizing selection (V(s,t)) are analyzed with a rare-alleles model. Both kinds of selection reduce V(G) but their roles in depleting it are not independent: The magnitude of pleiotropic selection depends on real stabilizing selection and such dependence is subject to the shape of the distributions of mutational effects. The genetic variation maintained thus depends on the kurtosis as well as the variance of mutational effects: All else being equal, V(G) increases with increasing leptokurtosis of mutational effects on fitness, while for a given distribution of mutational effects on fitness, V(G) decreases with increasing leptokurtosis of mutational effects on the trait. The V(G) and V(s,t) are determined primarily by real stabilizing selection while pleiotropic effects, which can be large, have only a limited impact. This finding provides some promise that a high heritability can be explained under strong total stabilizing selection for what are regarded as typical values of mutation and selection parameters. PMID:12242254

Zhang, Xu-Sheng; Hill, William G

2002-09-01

327

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

PubMed Central

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.

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

2010-01-01

328

Variations in type III effector repertoires, pathological phenotypes and host range of Xanthomonas citri pv. citri pathotypes.  

PubMed

The mechanisms determining the host range of Xanthomonas are still undeciphered, despite much interest in their potential roles in the evolution and emergence of plant pathogenic bacteria. Xanthomonas citri pv. citri (Xci) is an interesting model of host specialization because of its pathogenic variants: pathotype A strains infect a wide range of Rutaceous species, whereas pathotype A*/A(W) strains have a host range restricted to Mexican lime (Citrus aurantifolia) and alemow (Citrus macrophylla). Based on a collection of 55 strains representative of Xci worldwide diversity assessed by amplified fragment length polymorphism (AFLP), we investigated the distribution of type III effectors (T3Es) in relation to host range. We examined the presence of 66 T3Es from xanthomonads in Xci and identified a repertoire of 28 effectors, 26 of which were shared by all Xci strains, whereas two (xopAG and xopC1) were present only in some A*/A(W) strains. We found that xopAG (=avrGf1) was present in all A(W) strains, but also in three A* strains genetically distant from A(W) , and that all xopAG-containing strains induced the hypersensitive response (HR) on grapefruit and sweet orange. The analysis of xopAD and xopAG suggested horizontal transfer between X.?citri pv. bilvae, another citrus pathogen, and some Xci strains. A strains were genetically less diverse, induced identical phenotypic responses and possessed indistinguishable T3E repertoires. Conversely, A*/A(W) strains exhibited a wider genetic diversity in which clades correlated with geographical origin and T3E repertoire, but not with pathogenicity, according to T3E deletion experiments. Our data outline the importance of taking into account the heterogeneity of Xci?A*/A(W) strains when analysing the mechanisms of host specialization. PMID:23437976

Escalon, Aline; Javegny, Stéphanie; Vernière, Christian; Noël, Laurent D; Vital, Karine; Poussier, Stéphane; Hajri, Ahmed; Boureau, Tristan; Pruvost, Olivier; Arlat, Matthieu; Gagnevin, Lionel

2013-06-01

329

Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?  

PubMed Central

A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1 (Ca/04), a virus lethal in mice—herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations—which are also found in the 1918 and seasonal H1N1 viruses—in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.

Ye, Jianqiang; Sorrell, Erin M.; Cai, Yibin; Shao, Hongxia; Xu, Kemin; Pena, Lindomar; Hickman, Danielle; Song, Haichen; Angel, Matthew; Medina, Rafael A.; Manicassamy, Balaji; Garcia-Sastre, Adolfo; Perez, Daniel R.

2010-01-01

330

Quantitative radiography  

Microsoft Academic Search

We have developed a system of quantitative radiography in order to produce quantitative images displaying homogeneity of parts. The materials that we characterize are synthetic composites and may contain important subtle density variations not discernable by examining a raw film x-radiograph. In order to quantitatively interpret film radiographs, it is necessary to digitize, interpret, and display the images. Our integrated

C. M. Logan; J. M. Hernandez; G. J. Devine

1991-01-01

331

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

USGS Publications Warehouse

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.

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

2005-01-01

332

Epigenetic aspects of somaclonal variation in plants  

Microsoft Academic Search

Somaclonal variation is manifested as cytological abnormalities, frequent qualitative and quantitative phenotypic mutation, sequence change, and gene activation and silencing. Activation of quiescent transposable elements and retrotransposons indicate that epigenetic changes occur through the culture process. Epigenetic activation of DNA elements further suggests that epigenetic changes may also be involved in cytogenetic instability through modification of heterochromatin, and as a

Shawn M. Kaeppler; Heidi F. Kaeppler; Yong Rhee

2000-01-01

333

[Quantitative evaluation of the variation of aroma harmony in processed fruit and vegetable juices with gas chromatographic data].  

PubMed

To develop a quantitative evaluation model for the variation of aroma harmony in processed fruit and vegetable juices, gas chromatographic data from juice samples were summed up by mathematic modeling. Based on the original fruit and vegetable juices, the total change in volatile compounds expressed in term of percentage between the treated samples by various processes and the original juice, that is, the deviation of samples, are calculated. They were then used to describe the total change of aroma compounds in the fruit and vegetable juices before and after the processing. To compare the influences of different processes on aroma harmony in fruit and vegetable juices, the samples were analyzed by gas chromatography under the same conditions and the data were obtained by comparing the deviations of the samples. The lemon juices concentrated either by freeze-concentration or by vacuum evaporation were compared against the original lemon juices. The results showed that the freeze-concentration well retained not only the absolute contents of aroma compounds but also the aroma harmony of natural lemons. PMID:16250459

Liu, Ling; Cui, Mingxue; Xue, Yi

2005-07-01

334

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species  

PubMed Central

Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the dopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree. CSF HVA is an index of CNS dopamine activity, which is hypothesized to contribute substantially to behavioral variations in NHP and humans. For quantitative trait locus (QTL) mapping, we carried out a two-stage procedure. We first scanned the genome using a first-generation genetic map of short tandem repeat markers. Subsequently, using >100 SNPs within the most promising region identified by the genome scan, we mapped a QTL for CSF HVA at a genome-wide level of significance (peak logarithm of odds score >4) to a narrow well delineated interval (<10 Mb). The SNP discovery exploited conserved segments between human and rhesus macaque reference genome sequences. Our findings demonstrate the potential of using existing primate reference genome sequences for designing high-resolution genetic analyses applicable across a wide range of NHP species, including the many for which full genome sequences are not yet available. Leveraging genomic information from sequenced to nonsequenced species should enable the utilization of the full range of NHP diversity in behavior and disease susceptibility to determine the genetic basis of specific biological and behavioral traits.

Freimer, Nelson B.; Service, Susan K.; Ophoff, Roel A.; Jasinska, Anna J.; McKee, Kevin; Villeneuve, Amelie; Belisle, Alexandre; Bailey, Julia N.; Breidenthal, Sherry E.; Jorgensen, Matthew J.; Mann, J. John; Cantor, Rita M.; Dewar, Ken; Fairbanks, Lynn A.

2007-01-01

335

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species.  

PubMed

Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the dopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree. CSF HVA is an index of CNS dopamine activity, which is hypothesized to contribute substantially to behavioral variations in NHP and humans. For quantitative trait locus (QTL) mapping, we carried out a two-stage procedure. We first scanned the genome using a first-generation genetic map of short tandem repeat markers. Subsequently, using >100 SNPs within the most promising region identified by the genome scan, we mapped a QTL for CSF HVA at a genome-wide level of significance (peak logarithm of odds score >4) to a narrow well delineated interval (<10 Mb). The SNP discovery exploited conserved segments between human and rhesus macaque reference genome sequences. Our findings demonstrate the potential of using existing primate reference genome sequences for designing high-resolution genetic analyses applicable across a wide range of NHP species, including the many for which full genome sequences are not yet available. Leveraging genomic information from sequenced to nonsequenced species should enable the utilization of the full range of NHP diversity in behavior and disease susceptibility to determine the genetic basis of specific biological and behavioral traits. PMID:17884980

Freimer, Nelson B; Service, Susan K; Ophoff, Roel A; Jasinska, Anna J; McKee, Kevin; Villeneuve, Amelie; Belisle, Alexandre; Bailey, Julia N; Breidenthal, Sherry E; Jorgensen, Matthew J; Mann, J John; Cantor, Rita M; Dewar, Ken; Fairbanks, Lynn A

2007-10-01

336

Properties of the phenotypic variants of Pseudomonas aurantiaca and P. fluorescens  

Microsoft Academic Search

Different capacity for phenotypic variation of Pseudomonas aurantiaca and P. fluorescens in populations of cyst-like resting cells (CRC) during their germination on solid media, was shown to be a characteristic\\u000a trait of biodiversity for the dormant forms of these bacteria. This biodiversity manifests itself as qualitative and quantitative\\u000a differences in the spectra and emergence frequency of phenotype variants, obtained by

A. L. Mulyukin; A. N. Kozlova; G. I. El’-Registan

2008-01-01

337

Association of Mouse Dlg4 (PSD-95) Gene Deletion and Human DLG4 Gene Variation With Phenotypes Relevant to Autism Spectrum Disorders and Williams' Syndrome  

PubMed Central

Objective Research is increasingly linking autism spectrum disorders and other neurodevelopmental disorders to synaptic abnormalities (“synaptopathies”). PSD-95 (postsynaptic density-95, DLG4) orchestrates protein-protein interactions at excitatory synapses and is a major functional bridge interconnecting a neurexin-neuroligin-SHANK pathway implicated in autism spectrum disorders. Method The authors characterized behavioral, dendritic, and molecular phenotypic abnormalities relevant to autism spectrum disorders in mice with PSD-95 deletion (Dlg4?/?). The data from mice led to the identification of single-nucleotide polymorphisms (SNPs) in human DLG4 and the examination of associations between these variants and neural signatures of Williams’ syndrome in a normal population, using functional and structural neuroimaging. Results Dlg4?/? showed increased repetitive behaviors, abnormal communication and social behaviors, impaired motor coordination, and increased stress reactivity and anxiety-related responses. Dlg4?/? had subtle dysmorphology of amygdala dendritic spines and altered forebrain expression of various synaptic genes, including Cyln2, which regulates cytoskeletal dynamics and is a candidate gene for Williams’ syndrome. A significant association was observed between variations in two human DLG4 SNPs and reduced intraparietal sulcus volume and abnormal cortico-amygdala coupling, both of which characterize Williams’ syndrome. Conclusions These findings demonstrate that Dlg4 gene disruption in mice produces a complex range of behavioral and molecular abnormalities relevant to autism spectrum disorders and Williams’ syndrome. The study provides an initial link between human DLG4 gene variation and key neural endophenotypes of Williams’ syndrome and perhaps cortico-amygdala regulation of emotional and social processes more generally.

Feyder, Michael; Karlsson, Rose-Marie; Mathur, Poonam; Lyman, Matthew; Bock, Roland; Momenan, Reza; Munasinghe, Jeeva; Scattoni, Maria Luisa; Ihne, Jessica; Camp, Marguerite; Graybeal, Carolyn; Strathdee, Douglas; Begg, Alison; Alvarez, Veronica A.; Kirsch, Peter; Rietschel, Marcella; Cichon, Sven; Walter, Henrik; Meyer-Lindenberg, Andreas; Grant, Seth G.N.; Holmes, Andrew

2011-01-01

338

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

PubMed Central

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.

Sudarsanam, Priya; Cohen, Barak A.

2014-01-01

339

Phenotypic convergence along a gradient of predation risk  

PubMed Central

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.

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

2011-01-01

340

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

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

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

2003-02-01

341

Quantitative trait loci in hop (Humulus lupulus L.) reveal complex genetic architecture underlying variation in sex, yield and cone chemistry  

PubMed Central

Background Hop (Humulus lupulus L.) is cultivated for its cones, the secondary metabolites of which contribute bitterness, flavour and aroma to beer. Molecular breeding methods, such as marker assisted selection (MAS), have great potential for improving the efficiency of hop breeding. The success of MAS is reliant on the identification of reliable marker-trait associations. This study used quantitative trait loci (QTL) analysis to identify marker-trait associations for hop, focusing on traits related to expediting plant sex identification, increasing yield capacity and improving bittering, flavour and aroma chemistry. Results QTL analysis was performed on two new linkage maps incorporating transferable Diversity Arrays Technology (DArT) markers. Sixty-three QTL were identified, influencing 36 of the 50 traits examined. A putative sex-linked marker was validated in a different pedigree, confirming the potential of this marker as a screening tool in hop breeding programs. An ontogenetically stable QTL was identified for the yield trait dry cone weight; and a QTL was identified for essential oil content, which verified the genetic basis for variation in secondary metabolite accumulation in hop cones. A total of 60 QTL were identified for 33 secondary metabolite traits. Of these, 51 were pleiotropic/linked, affecting a substantial number of secondary metabolites; nine were specific to individual secondary metabolites. Conclusions Pleiotropy and linkage, found for the first time to influence multiple hop secondary metabolites, have important implications for molecular selection methods. The selection of particular secondary metabolite profiles using pleiotropic/linked QTL will be challenging because of the difficulty of selecting for specific traits without adversely changing others. QTL specific to individual secondary metabolites, however, offer unequalled value to selection programs. In addition to their potential for selection, the QTL identified in this study advance our understanding of the genetic control of traits of current economic and breeding significance in hop and demonstrate the complex genetic architecture underlying variation in these traits. The linkage information obtained in this study, based on transferable markers, can be used to facilitate the validation of QTL, crucial to the success of MAS.

2013-01-01

342

Further studies of the relationships among strains classified as taxon 15, taxon 18, taxon 20, (Pasteurella) granulomatis or the (Pasteurella) haemolytica-complex in ruminants using quantitative evaluation of phenotypic data.  

PubMed

Ninety-three trehalose-negative (P.) haemolytica-like strains of ruminant, porcine and leprine origin were investigated. A quantitative evaluation of phenotypic tests was used and the results obtained were compared with those from 246 previously investigated ruminant strains. Cluster analysis of the results obtained displayed most of the taxa as distinct groups which could be related to differences in key characters. Although only minor phenotypic differences were observed between the taxa investigated and the taxa were internally heterogeneous for many of the tests, it was possible to identify characters separating most groups. However, in three instances, taxa isolated from different species could not be separated by any of the tests used or by quantitative evaluation of all 79 tests--the only difference being the species of animals from which they had been isolated. Taxa which could not be separated by phenotypic tests included the ruminant biogroup 6 of (P.) haemolytica and the porcine taxon 15/biovar 1, the ruminant biogroup 7 of (P.) haemolytica and the porcine taxon 15/biovar 2, and ruminant biogroup 31 of (P.) haemolytica and the leprine taxon 20/biovar 1. PMID:9361379

Angen, O; Olsen, J E; Bisgaard, M

1997-10-01

343

Molecular and Quantitative Genetic Differentiation in European Populations of Silene latifolia (Caryophyllaceae)  

PubMed Central

Background and Aims Among-population differentiation in phenotypic traits and allelic variation is expected as a consequence of isolation, drift, founder effects and local selection. Therefore, investigating molecular and quantitative genetic divergence is a pre-requisite for studies of local adaptation in response to selection under variable environmental conditions. Methods Among- and within-population variation were investigated in six geographically separated European populations of the white campion, Silene latifolia, both for molecular variation at six newly developed microsatellite loci and for quantitative variation in morphological and life-history traits. To avoid confounding effects of the maternal environment, phenotypic traits were measured on greenhouse-reared F1 offspring. Tests were made for clinal variation, and the correlations among molecular, geographic and phenotypic distances were compared with Mantel tests. Key Results The six populations of Silene latifolia investigated showed significant molecular and quantitative genetic differentiation. Geographic and phenotypic distances were significantly associated. Age at first flowering increased significantly with latitude and exhibited a Qst value of 0·17 in females and 0·10 in males, consistent with adaptation to local environmental conditions. By contrast, no evidence of isolation-by-distance and no significant association between molecular and phenotypic distances were found. Conclusions Significant molecular genetic divergence among populations of Silene latifolia, from the European native range is consistent with known limited seed and pollen flow distances, while significant quantitative genetic divergence among populations and clinal variation for age at first flowering suggest local adaptation.

Jolivet, Celine; Bernasconi, Giorgina

2007-01-01

344

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

Microsoft Academic Search

Developmental mechanisms are usually assumed to evolve by natural selection of the morphological traits they produce. Therefore, information on phenotypic traits is an important component of comparative studies of development. 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

Christian Peter Klingenberg

2002-01-01

345

SpA, ClfA, and FnbA genetic variations lead to Staphaurex test-negative phenotypes in bovine mastitis Staphylococcus aureus isolates.  

PubMed

Staphylococcus aureus encodes many proteins that act as virulence factors, leading to a variety of diseases, including mastitis in cows. Among these virulence factors, SpA, ClfA, ClfB, FnbA, and FnbB are important for the ability of S. aureus to adhere to and invade host cells as well as to evade host immune responses. The interaction between these S. aureus surface proteins and human immunoglobulin G and fibrinogen that are coupled to latex particles is utilized to induce latex agglutination reactions, which are used widely in diagnostic kits for confirmation of presumptive S. aureus isolates. In this study, the Staphaurex latex agglutination test was performed on a collection of confirmed bovine mastitis S. aureus isolates. Notably, 54% (43/79 isolates) of these isolates exhibited latex agglutination-negative phenotypes (Staphaurex-negative result). To gain insights into the reasons for the high frequency of Staphaurex-negative bovine mastitis S. aureus isolates, the spa, clfA, clfB, fnbA, and fnbB genes were examined. Specific genetic changes in spa, clfA, and fnbA, as well as a loss of fnbB, which may impair SpA, ClfA, FnbA, and FnbB functions in latex agglutination reactions, were detected in Staphaurex-negative S. aureus isolates. The genetic changes included a premature stop codon in the spa gene, leading to a truncated SpA protein that is unable to participate in S. aureus cell-mediated agglutination of latex particles. In addition, clfA and fnbA genetic polymorphisms were detected that were linked to ClfA and FnbA amino acid changes that may significantly reduce fibrinogen-binding activity. The genetic variations in these S. aureus isolates might also have implications for their bovine mastitis virulence capacity. PMID:21147952

Stutz, Katrin; Stephan, Roger; Tasara, Taurai

2011-02-01

346

SpA, ClfA, and FnbA Genetic Variations Lead to Staphaurex Test-Negative Phenotypes in Bovine Mastitis Staphylococcus aureus Isolates?  

PubMed Central

Staphylococcus aureus encodes many proteins that act as virulence factors, leading to a variety of diseases, including mastitis in cows. Among these virulence factors, SpA, ClfA, ClfB, FnbA, and FnbB are important for the ability of S. aureus to adhere to and invade host cells as well as to evade host immune responses. The interaction between these S. aureus surface proteins and human immunoglobulin G and fibrinogen that are coupled to latex particles is utilized to induce latex agglutination reactions, which are used widely in diagnostic kits for confirmation of presumptive S. aureus isolates. In this study, the Staphaurex latex agglutination test was performed on a collection of confirmed bovine mastitis S. aureus isolates. Notably, 54% (43/79 isolates) of these isolates exhibited latex agglutination-negative phenotypes (Staphaurex-negative result). To gain insights into the reasons for the high frequency of Staphaurex-negative bovine mastitis S. aureus isolates, the spa, clfA, clfB, fnbA, and fnbB genes were examined. Specific genetic changes in spa, clfA, and fnbA, as well as a loss of fnbB, which may impair SpA, ClfA, FnbA, and FnbB functions in latex agglutination reactions, were detected in Staphaurex-negative S. aureus isolates. The genetic changes included a premature stop codon in the spa gene, leading to a truncated SpA protein that is unable to participate in S. aureus cell-mediated agglutination of latex particles. In addition, clfA and fnbA genetic polymorphisms were detected that were linked to ClfA and FnbA amino acid changes that may significantly reduce fibrinogen-binding activity. The genetic variations in these S. aureus isolates might also have implications for their bovine mastitis virulence capacity.

Stutz, Katrin; Stephan, Roger; Tasara, Taurai

2011-01-01

347

Evidence for adaptive phenotypic differentiation in Baltic Sea sticklebacks.  

PubMed

The evidence for adaptive phenotypic differentiation in mobile marine species remains scarce, partly due to the difficulty of obtaining quantitative genetic data to demonstrate the genetic basis of the observed phenotypic differentiation. Using a combination of phenotypic and molecular genetic approaches, we elucidated the relative roles of natural selection and genetic drift in explaining lateral plate number differentiation in threespine sticklebacks (Gasterosteus aculeatus) across the entire Baltic Sea basin (approximately 392 000 km(2) ). We found that phenotypic differentiation (PST  = 0.213) in plate number exceeded that in neutral markers (FST  = 0.008), suggesting an adaptive basis for the observed differentiation. Because a close correspondence was found between plate phenotype and genotype at a quantitative trait loci (QTL; STN381) tightly linked to the gene (Ectodysplasin) underlying plate variation, the evidence for adaptive differentiation was confirmed by comparison of FST at the QTL (FSTQ  = 0.089) with FST at neutral marker loci. Hence, the results provide a comprehensive demonstration of adaptive phenotypic differentiation in a high-gene-flow marine environment with direct, rather than inferred, verification for the genetic basis of this differentiation. In general, the results illustrate the utility of PST -FST -FSTQ comparisons in uncovering footprints of natural selection and evolution and add to the growing evidence for adaptive genetic differentiation in high-gene-flow marine environments, including that of the relatively young Baltic Sea. PMID:23859314

Defaveri, J; Merilä, J

2013-08-01

348

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

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…

Freudenthal, Daniel: Pine, Julian; Gobet, Fernando

2010-01-01

349

Genotype-Phenotype Map Characteristics of an In silico Heart Cell  

PubMed Central

Understanding the causal chain from genotypic to phenotypic variation is a tremendous challenge with huge implications for personalized medicine. Here we argue that linking computational physiology to genetic concepts, methodology, and data provides a new framework for this endeavor. We exemplify this causally cohesive genotype–phenotype (cGP) modeling approach using a detailed mathematical model of a heart cell. In silico genetic variation is mapped to parametric variation, which propagates through the physiological model to generate multivariate phenotypes for the action potential and calcium transient under regular pacing, and ion currents under voltage clamping. The resulting genotype-to-phenotype map is characterized using standard quantitative genetic methods and novel applications of high-dimensional data analysis. These analyses reveal many well-known genetic phenomena like intralocus dominance, interlocus epistasis, and varying degrees of phenotypic correlation. In particular, we observe penetrance features such as the masking/release of genetic variation, so that without any change in the regulatory anatomy of the model, traits may appear monogenic, oligogenic, or polygenic depending on which genotypic variation is actually present in the data. The results suggest that a cGP modeling approach may pave the way for a computational physiological genomics capable of generating biological insight about the genotype–phenotype relation in ways that statistical-genetic approaches cannot.

Vik, Jon Olav; Gjuvsland, Arne B.; Li, Liren; T?ndel, Kristin; Niederer, Steven; Smith, Nicolas P.; Hunter, Peter J.; Omholt, Stig W.

2011-01-01

350

Genetic and Molecular Analyses of Natural Variation Indicate CBF2 as a Candidate Gene for Underlying a Freezing Tolerance Quantitative Trait Locus in Arabidopsis1[w  

PubMed Central

Natural variation for freezing tolerance is a major component of adaptation and geographic distribution of plant species. However, little is known about the genes and molecular mechanisms that determine its naturally occurring diversity. We have analyzed the intraspecific freezing tolerance variation existent between two geographically distant accessions of Arabidopsis (Arabidopsis thaliana), Cape Verde Islands (Cvi) and Landsberg erecta (Ler). They differed in their freezing tolerance before and after cold acclimation, as well as in the cold acclimation response in relation to photoperiod conditions. Using a quantitative genetic approach, we found that freezing tolerance differences after cold acclimation were determined by seven quantitative trait loci (QTL), named FREEZING TOLERANCE QTL 1 (FTQ1) to FTQ7. FTQ4 was the QTL with the largest effect detected in two photoperiod conditions, while five other FTQ loci behaved as photoperiod dependent. FTQ4 colocated with the tandem repeated genes C-REPEAT BINDING FACTOR 1 (CBF1), CBF2, and CBF3, which encode transcriptional activators involved in the cold acclimation response. The low freezing tolerance of FTQ4-Cvi alleles was associated with a deletion of the promoter region of Cvi CBF2, and with low RNA expression of CBF2 and of several CBF target genes. Genetic complementation of FTQ4-Cvi plants with a CBF2-Ler transgene suggests that such CBF2 allelic variation is the cause of CBF2 misexpression and the molecular basis of FTQ4.

Alonso-Blanco, Carlos; Gomez-Mena, Concepcion; Llorente, Francisco; Koornneef, Maarten; Salinas, Julio; Martinez-Zapater, Jose M.

2005-01-01

351

Variation, selection and evolution of function-valued traits  

Microsoft Academic Search

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,

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

2001-01-01

352

Variation, selection and evolution of function-valued traits  

Microsoft Academic Search

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,

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

2001-01-01

353

Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate  

PubMed Central

Kinesin-5 inhibitors (K5Is) are promising anti-mitotic cancer drug candidates. They cause prolonged mitotic arrest and death of cancer cells, but their full range of phenotypic effects in different cell types has been unclear. Using time-lapse microscopy of cancer and normal cell lines, we find that a novel K5I causes several different cancer and non-cancer cell types to undergo prolonged arrest in monopolar mitosis. Subsequent events, however, differed greatly between cell types. Normal diploid cells mostly slipped from mitosis and arrested in tetraploid G1, with little cell death. Several cancer cell lines either died during mitotic arrest, or following slippage. Contrary to prevailing views, mitotic slippage was not required for death, and the duration of mitotic arrest correlated poorly with the probability of death in most cell lines. We also assayed drug reversibility, and long-term responses after transient drug exposure in MCF7 breast cancer cells. While many cells divided after drug washout during mitosis, this treatment resulted in lower survival compared to washout after spontaneous slippage, likely due to chromosome segregation errors in the cells that divided. Our analysis shows that K5Is cause cancer-selective cell killing, provides important kinetic information for understanding clinical responses, and elucidates mechanisms of drug sensitivity versus resistance at the level of phenotype.

Tang, Yangzhong; Shi, Jade; Loy, Clement T.; Amendt, Christiane; Wilm, Claudia; Zenke, Frank T.; Mitchison, Timothy J.

2008-01-01

354

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

ERIC Educational Resources Information Center

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…

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

2014-01-01

355

Quantitative genetic variation of leaf size and shape in a mixed diploid and triploid population of Populus.  

PubMed

In the interspecific cross of Populus trichocarpa x P. deltoides, unexpected simultaneous occurrence of diploid hybrids and triploid hybrids (with two alleles from the female parent and one from the male parent at each locus) led us to examine the evolutionary genetic significance of this phenomenon. As expected, leaf size and shape of the triploid progeny are closer to the female P. trichocarpa than male P. deltoides parent. Although the pure triploid progeny population did not have higher genetic variance in leaf traits than the pure diploid population, the former appears to hide much non-additive genetic variance and display strong genetic control over the phenotypic plasticity of leaf traits. It is suggested that the cryptic non-additive variance, especially epistasis, can be released when a population is disturbed by changes in the environment. A mixed diploid and triploid progeny population combines phenotypic and genetic characteristics of both pure hybrids and is considered to be of adaptive significance for populars to survive and evolve in a fluctuating environment. The significant effect due to general and specific combining ability differences at the population level suggests that the population divergence of these two species is under additive and non-additive genetic control. PMID:10816978

Wu, R L

2000-04-01

356

Molecular and phenotypic characterization of near isogenic lines at QTL for quantitative resistance to Leptosphaeria maculans in oilseed rape (Brassica napus L.).  

PubMed

The most common and effective way to control phoma stem canker (blackleg) caused by Leptosphaeria maculans in oilseed rape (Brassica napus) is by breeding resistant cultivars. Specific resistance genes have been identified in B. napus and related species but in some B. napus cultivars resistance is polygenic [mediated by quantitative trait loci (QTL)], postulated to be race non-specific and durable. The genetic basis of quantitative resistance in the French winter oilseed rape 'Darmor', which was derived from 'Jet Neuf', was previously examined in two genetic backgrounds. Stable QTL involved in blackleg resistance across year and genetic backgrounds were identified. In this study, near isogenic lines (NILs) were produced in the susceptible background 'Yudal' for four of these QTL using marker-assisted selection. Various strategies were used to develop new molecular markers, which were mapped in these QTL regions. These were used to characterize the length and homozygosity of the 'Darmor-bzh' introgressed segment in the NILs. Individuals from each NIL were evaluated in blackleg disease field trials and assessed for their level of stem canker in comparison to the recurrent line 'Yudal'. The effect of QTL LmA2 was clearly validated and to a lesser extent, QTL LmA9 also showed an effect on the disease level. This work provides valuable material that can be used to study the mode of action of genetic factors involved in L. maculans quantitative resistance. PMID:18696043

Delourme, R; Piel, N; Horvais, R; Pouilly, N; Domin, C; Vallée, P; Falentin, C; Manzanares-Dauleux, M J; Renard, M

2008-11-01

357

A quantitative genetic and epigenetic model of complex traits  

PubMed Central

Background Despite our increasing recognition of the mechanisms that specify and propagate epigenetic states of gene expression, the pattern of how epigenetic modifications contribute to the overall genetic variation of a phenotypic trait remains largely elusive. Results We construct a quantitative model to explore the effect of epigenetic modifications that occur at specific rates on the genome. This model, derived from, but beyond, the traditional quantitative genetic theory that is founded on Mendel’s laws, allows questions concerning the prevalence and importance of epigenetic variation to be incorporated and addressed. Conclusions It provides a new avenue for bringing chromatin inheritance into the realm of complex traits, facilitating our understanding of the means by which phenotypic variation is generated.

2012-01-01

358

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

DOEpatents

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.

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

2002-01-01

359

Quantitative genetic variation of metabolism in the nymphs of the sand cricket, Gryllus firmus, inferred from an analysis of inbred-lines.  

PubMed

Compared with morphological and life history traits, quantitative genetic variation of metabolic and related traits in animals has been poorly studied. We used flow-through VCO(2) respirometry and simultaneous activity measurement on nymphs of the sand cricket (Gryllus firmus) from inbred lines to estimate broad-sense heritability of four metabolic variables. In addition, we measured a number of linear dimensions in the adults from the same inbred lines. There were significant multivariate effects of inbred lines for all traits and broad-sense heritability for physiological traits was 4.5%, 5.2%, 10.3% and 8.5% for average, resting, minimum and maximum CO(2) production in nymphs, respectively. Though the MANOVA indicated significant genetic variation among inbred lines in adult morphology, the broad-sense heritabilities were relatively low ranging from 0-18%. Our results indicate that the heritabilities of metabolic measures are large enough to potentially respond to selection. PMID:17657350

Nespolo, Roberto F; Castañeda, Luis E; Roff, Derek A

2007-01-01

360

Quantitative developmental genetic analysis reveals that the ancestral dipteran wing vein prepattern is conserved in Drosophila melanogaster  

Microsoft Academic Search

Quantitative complementation tests provide a quick test of the hypothesis that a particular gene contributes to segregating\\u000a phenotypic variation. A set of wild-type alleles is assayed for variation in their ability to complement the degree of dominance\\u000a of the quantitative effect of a loss of function allele. Analysis of 15 loci known to be involved in wing patterning in Drosophila

Arnar Palsson; Greg Gibson

2000-01-01