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1

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

2

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

PubMed

The vacuolated lens (vl) mouse mutant arose spontaneously on the C3H/HeSn background and exhibits neural tube defects (NTDs), congenital cataract, and occasionally a white belly spot. We previously reported that 1) the vl phenotypes are due to a mutation in an orphan G protein-coupled receptor (GPCR), Gpr161; 2) the penetrance of the vl NTD and cataract phenotypes are affected by genetic background, allowing three unlinked quantitative trait loci (QTL) to be mapped (modifiers of vacuolated lens, Modvl1-3); and 3) phenotype-based bioinformatics followed by genetic and molecular analysis identified a lens-specific transcription factor that contributes to the cataract-modifying effect of Modvl3. We now extend this analysis in three ways. First, using the Gpr161 mutation to unequivocally identify mutant adults and embryos, we determined that approximately 50% of vl/vl NTD-affected embryos die during development. Second, the MOLF/Ei genetic background suppresses this embryonic lethality but increases the incidence of the adult belly spot phenotype. Additional QTL analysis was performed, and two novel modifiers were mapped [Modvl4, logarithm of odds ratio (LOD) 4.4; Modvl5, LOD 5.0]. Third, phenotype-based bioinformatics identified candidate genes for these modifiers including two GPCRs that cause NTD or skin/pigmentation defects (Modvl4: Frizzled homolog 6; Modvl5: Melanocortin 5 receptor). Because GPCRs form oligomeric complexes, these genes were resequenced and nonsynonymous coding variants were identified. Bioinformatics and protein modeling suggest that these variants may be functional. Our studies further establish vl as a multigenic mouse model for NTDs and identify additional QTL that interact with Gpr161 to regulate neurulation. PMID:18796533

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

2008-09-16

3

Phenotypic variation and quantitative trait locus identification for osmotic potential in an interspecific hybrid inbred F2 poplar pedigree grown in contrasting environments  

SciTech Connect

Elucidation of the mechanisms of dehydration tolerance in popular (Populus sp.) trees will permit development of biochemical and molecular indicators to indentify dehydration-tolerant genotypes during genetic selection. The objectives of the study were to characterize the degree of phenotypic variation in osmotic potential (a determinant of dehydration tolerance), determine the relationship between osmotic potential at full turgor and relative growth rate, and identify quantitative trait loci (QTL) for osmotic potential in an advanced-generation, interpsecific popular pedigree established in contrasting environments.

Tschaplinski, Timothy J [ORNL; Tuskan, Gerald A [ORNL; Sewell, Mitchell [ORNL; Gebre, G [ORNL; Todd Jr, Donald E [ORNL; Pendley, Carrie D [ORNL

2006-01-01

4

Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions  

PubMed Central

During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ?500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus.

Giurumescu, Claudiu A.; Sternberg, Paul W.; Asthagiri, Anand R.

2009-01-01

5

Phenotypic and genetic variations in crown-gall tumour cells of tobacco  

Microsoft Academic Search

Phenotypic and genetic variations of tumour cells were analysed both quantitatively and qualitatively in clones and subclones of a crown-gall strain. Thus, growth rates, grafting tests, octopine synthesis, estimations of the T-DNA contents, modifications in the numbers, and structures of chromosomes were examined. Phenotypic variations are closely associated with genetic changes, including variation in chromosome number (which is shown to

A. Mouras; I. Negrutiu; Y. Dessaux

1987-01-01

6

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

7

Quantitative measurement of variational approximations  

Microsoft Academic Search

Variational problems have long been used to mathematically model physical systems. Their advantage has been the simplicity of the model as well as the ability to deduce information concerning the functional dependence of the system on various parameters embedded in the variational trial functions. However, the only method in use for estimating the error in a variational approximation has been

D. J. Kaup; T. K. Vogel

2007-01-01

8

Variations in genotype-phenotype correlations in phenylketonuria patients  

Microsoft Academic Search

Phenylalanine hydroxylase deficiency is a trait inherited in an autosomal recessive pattern; the associated phenotype varies con- siderably. This variation is mainly due to the considerable allelic hetero- geneity in the phenylalanine hydroxylase enzyme locus. We examined the genotype-phenotype correlation in 54 phenylketonuria (PKU) pa- tients from Minas Gerais, Brazil. Two systems were used. The first was a phenotype prediction

L. L. Santos; C. G. Fonseca; A. L. P. Starling; M. J. B. Aguiar; M. G. C. D. Peixoto; M. R. S. Carvalho

2010-01-01

9

Linking post-translational modifications and variation of phenotypic traits.  

PubMed

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

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

2012-12-27

10

Drosophila bristles and the nature of quantitative genetic variation  

PubMed Central

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.

Mackay, Trudy F.C; Lyman, Richard F

2005-01-01

11

Which evolutionary processes influence natural genetic variation for phenotypic traits?  

Microsoft Academic Search

Although many studies provide examples of evolutionary processes such as adaptive evolution, balancing selection, deleterious variation and genetic drift, the relative importance of these selective and stochastic processes for phenotypic variation within and among populations is unclear. Theoretical and empirical studies from humans as well as natural animal and plant populations have made progress in examining the role of these

John H. Willis; Thomas Mitchell-Olds

2007-01-01

12

[Ehlers-Danlos syndrome IV: phenotype variation].  

PubMed

In three female patients, 20, 4 and 29 years of age, Ehlers-Danlos syndrome (EDS) IV was diagnosed on the basis of a deficiency of collagen III with among other things a hyperextensible skin and joints and easy bruising. Severity of symptoms varies considerably per patient. EDS comprises 10 types. Type IV is the most severe type because of its often lethal complications like arterial rupture. Deficiency of collagen III is also seen in EDS patients without the classical severe EDS IV phenotype. It is suggested to restrict collagen III analysis to patients who are suspected of having classical EDS IV. PMID:9148166

Engels, C H; van Dongen, P W; Boers, G H; Steijlen, P M; Hamel, B C

1997-02-01

13

Extracting quantitative genetic interaction phenotypes from matrix combinatorial RNAi  

PubMed Central

Background Systematic measurement of genetic interactions by combinatorial RNAi (co-RNAi) is a powerful tool for mapping functional modules and discovering components. It also provides insights into the role of epistasis on the way from genotype to phenotype. The interpretation of co-RNAi data requires computational and statistical analysis in order to detect interactions reliably and sensitively. Results We present a comprehensive approach to the analysis of univariate phenotype measurements, such as cell growth. The method is based on a quantitative model and is demonstrated on two example Drosophila cell culture data sets. We discuss adjustments for technical variability, data quality assessment, model parameter fitting and fit diagnostics, choice of scale, and assessment of statistical significance. Conclusions As a result, we obtain quantitative genetic interactions and interaction networks reflecting known biological relationships between target genes. The reliable extraction of presence, absence, and strength of interactions provides insights into molecular mechanisms.

2011-01-01

14

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

NSDL National Science Digital Library

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

CYNTHIA WEINIG and JOHANNA SCHMITT (;)

2004-07-01

15

Phenotypic variation in Azospirillum brasilense exposed to starvation.  

PubMed

Bacteria have developed mechanisms that allow them maintaining cell viability during starvation and resuming growth when nutrients become available. Among these mechanisms are adaptive mutations and phase variation, which are often associated with DNA rearrangements. Azospirillum brasilense is a Gram-negative, nitrogen-fixing, plant growth-promoting rhizobacterium. Here we report phenotypic variants of A. brasilense that were collected after exposure to prolonged starvation or after re-isolation from maize roots. The variants differed in several features from the parental strains, including pigmentation, aggregation ability, EPS amount and composition and LPS structure. One of the phenotypic variants, overproducing EPS and showing an altered LPS structure, was further characterized and showed differential response to several stresses and antibiotics relative to its parental strain. Characterization of the variants by repetitive-PCR revealed that phenotypic variation was often associated with DNA rearrangements. PMID:23766228

Lerner, Anat; Valverde, Angel; Castro-Sowinski, Susana; Lerner, Hadas; Okon, Yaacov; Burdman, Saul

2010-03-01

16

Molar Intercuspal Dimensions: Genetic Input to Phenotypic Variation  

Microsoft Academic Search

Molecular studies indicate that epigenetic events are important in determining how the internal enamel epithelium folds during odontogenesis. Since this process of folding leads to the subsequent arrangement of cusps on molar teeth, we hypothesized that intercuspal distances of human molar teeth would display greater phenotypic variation but lower heritabilities than overall crown diameters. Intercuspal distances and maximum crown diameters

G. Townsend; L. Richards; T. Hughes

2003-01-01

17

Causes of Variation in the Cystic Fibrosis Phenotype  

Microsoft Academic Search

Cystic fibrosis (CF) is caused by abnormal function of the CF transmembrane conductance regulator (CFTR) gene. CF is highly variable with some individuals succumbing to the disease in their first decade while others live into their fourth and fifth decades. Patients also differ in the involvement of organ systems and in complications. Some of the variation in CF phenotype can

Garry R. Cutting

2006-01-01

18

Phenotypic Variation of Fluoride Responses between Inbred Strains of Mice  

PubMed Central

Excessive systemic exposure to fluoride (F) can lead to disturbances in bone homeostasis and dental enamel development. We have previously shown strain-specific responses to F in the development of dental fluorosis (DF) and in bone formation/mineralization. The current study was undertaken to further investigate F responsive variations in bone metabolism and to determine possible relationships with DF susceptibility. Seven-week-old male mice from FVB/NJ, C57BL/6J, C3H/HeJ, A/J, 129S1/SvImJ, AKR/J, DBA/2J, and BALB/cByJ inbred strains were exposed to NaF (0 or 50 ppm as F–) in drinking water for 60 days. Sera were collected for F, Ca, Mg, PO4, iPTH, sRANKL, and ALP levels. Bone marrow cells were subjected to ex vivo cell culture for osteoclast potential and CFU colony assays (CFU-fibroblast, CFU-osteoblast, CFU-erythrocyte/granulocyte/macrophage/megakaryocyte, CFU-granulocyte/macrophage, CFU-macrophage, and CFU-granulocyte). Femurs and vertebrae were subjected to micro-CT analyses, biomechanical testing, and F, Mg, and Ca content assays. DF was evaluated using quantitative fluorescence and clinical criteria. Strain-specific responses to F were observed for DF, serum studies, ex vivo cell culture studies, and bone quality. Among the strains, there were no patterns or significant correlations between DF severity and the actions of F on bone homeostasis (serum studies, ex vivo assays, or bone quality parameters). The genetic background continues to play a role in the actions of F on tooth enamel development and bone homeostasis. F exposure led to variable phenotypic responses between strains involving dental enamel development and bone metabolism.

Yan, Dong; Willett, Thomas L.; Gu, Xiao-Mei; Martinez-Mier, E. Angeles; Sardone, Laura; McShane, Lauren; Grynpas, Marc; Everett, Eric T.

2011-01-01

19

Natural Variation of Model Mutant Phenotypes in Ciona intestinalis  

PubMed Central

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

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

2008-01-01

20

Linkage analysis merging replicate phenotypes: an application to three quantitative phenotypes in two African samples  

PubMed Central

We report two approaches for linkage analysis of data consisting of replicate phenotypes. The first approach is specifically designed for the unusual (in human data) replicate structure of the Genetic Analysis Workshop 17 pedigree data. The second approach consists of a standard linkage analysis that, although not specifically tailored to data consisting of replicate genotypes, was envisioned as providing a sounding board against which our novel approach could be assessed. Both approaches are applied to the analysis of three quantitative phenotypes (Q1, Q2, and Q4) in two sets of African families. All analyses were carried out blind to the generating model (i.e., the “answers”). Using both methods, we found numerous significant linkage signals for Q1, although population colocalization was absent for most of these signals. The linkage analysis of Q2 and Q4 failed to reveal any strong linkage signals.

2011-01-01

21

Phenotypic Variation in a Large Family with Autosomal Dominant Hypocalcaemia  

Microsoft Academic Search

Background\\/Aims: Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium- sensing receptor (CASR). We aimed to describe the phenotypic variation within a large family with ADH, especially kidney and cerebral basal ganglia calcifications. Methods: Fifteen related subjects carrying the CASR mutation T151M participated in a cross-sectional study of calcium homeostasis, renal ultrasonography, cerebral CT, bone mineral density,

J. I. Sørheim; E. S. Husebye; B. G. Nedrebø; E. Svarstad; J. Lind; H. Boman; K. Løvås

2010-01-01

22

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

23

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

PubMed Central

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

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

2012-01-01

24

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

2013-09-02

25

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

26

Evolution of adaptive phenotypic variation patterns by direct selection for evolvability  

PubMed Central

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.

Pavlicev, Mihaela; Cheverud, James M.; Wagner, Gunter P.

2011-01-01

27

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

PubMed

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. PMID:23306084

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

2013-01-10

28

Phenotypic variation of tuberous sclerosis in a single extended kindred.  

PubMed Central

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a great degree of phenotypic variability. Given the presence of two gene loci underlying this disorder, locus heterogeneity may account for some of the variability. However, significant within family variation suggests that different genes do not explain the majority of this variation. The purpose of this research is to identify physical and behavioural variation in expression of TSC in a single large extended kindred. TSC in this kindred is cosegregating with markers localised to chromosome 16p13.3. The expression of TSC in this kindred is quite variable with a substantial proportion of persons showing very mild physical expression of TSC. In contrast to very mild physical expression of TSC in some family members, there is a significant clustering of psychiatric disorders among persons affected with TSC compared to their unaffected relatives. This finding, coupled with the mild physical expression of TSC in some family members, supports a hypothesis that the TSC2 gene may present phenotypically as mild skin signs and significant behavioural problems.

Smalley, S L; Burger, F; Smith, M

1994-01-01

29

Understanding phenotypic variation in rodent models with germline Apc mutations.  

PubMed

Adenomatous polyposis coli (APC) is best known for its crucial role in colorectal cancer suppression. Rodent models with various Apc mutations have enabled experimental validation of different Apc functions in tumors and normal tissues. Since the development of the first mouse model with a germline Apc mutation in the early 1990s, 20 other Apc mouse and rat models have been generated. This article compares and contrasts currently available Apc rodent models with particular emphasis on providing potential explanations for their reported variation in three areas: (i) intestinal polyp multiplicity, (ii) intestinal polyp distribution, and (iii) extraintestinal phenotypes. PMID:23580574

Zeineldin, Maged; Neufeld, Kristi L

2013-04-11

30

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

PubMed

Alternative splicing (AS) of pre-messenger RNA is a common phenomenon that creates different transcripts from a single gene, and these alternative transcripts affect phenotypes. The majority of AS research has examined tissue and developmental specificity of expression of particular AS transcripts, how this specificity affects cell function, and how aberrant AS is related to disease. Few studies have examined quantitative between-individual variation in AS within a cell or tissue type, or in relation to phenotypes, but the results are compelling: quantitative variation in AS affects plastic traits such as stress, anxiety, fear, egg production, muscle performance, energetics and plant growth. Genomic analyses of AS are also at a nascent stage, but have revealed a number of significant evolutionary patterns. Growing knowledge of upstream genes and kinases that regulate AS provides the as-yet little explored potential to examine how these genes and pathways respond to environmental and genotype variables. Research in this area can provide glimpses of a labyrinth of genetic architectures that have rarely been considered in evolutionary and organismal biology, or in quantitative genetics. The scarcity of contribution to knowledge about AS from these fields is illustrated by the fact that heritability of quantitative variation in AS has not yet been determined for any gene in any organism. New research tactics that incorporate quantitative analyses of AS will allow organismal and evolutionary biologists to attain a fuller mechanistic understanding of many of the traits they study, and may lead to more rapid discovery of functionally important polymorphisms. PMID:17006532

Marden, J H

2006-09-27

31

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

32

Mutations and quantitative genetic variation: lessons from Drosophila  

PubMed Central

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.

Mackay, Trudy F. C.

2010-01-01

33

Evolution of pleiotropy: Epistatic interaction pattern supports a mechanistic model underlying variation in genotype-phenotype map  

PubMed Central

The genotype-phenotype map consists of developmental and physiological mechanisms mapping genetic onto phenotypic variation. It determines the distribution of heritable phenotypic variance on which selection can act. Comparative studies of morphology as well as of gene regulatory networks show that the genotype-phenotype map itself evolves, yet little is known about the actual evolutionary mechanisms involved. The study of such mechanisms requires exploring the variation in genotype-phenotype maps at the population level, which presently is easier to quantify by statistical genetic methods rather than by regulatory network structures. We focus on the evolution of pleiotropy, a major structural aspect of the genotype-phenotype map. Pleiotropic genes affect multiple traits and underlie genetic covariance between traits, often causing evolutionary constraints. Previous quantitative genetic studies have demonstrated population-level variation in pleiotropy in the form of loci, at which genotypes differ in the genetic covariation between traits. This variation can potentially fuel evolution of the genotype-phenotype map under selection and/or drift. Here, we propose a developmental mechanism underlying population genetic variation in covariance, and test its predictions. Specifically, the mechanism predicts that the loci identified as responsible for genetic variation in pleiotropy are involved in trait-specific epistatic interactions. We test this prediction for loci affecting allometric relationships between traits in an advanced intercross between inbred mouse strains. The results consistently support the prediction. We further find a high degree of sign epistasis in these interactions, which we interpret as an indication of adaptive gene complexes within the diverged parental lines.

Pavlicev, Mihaela; Norgard, Elizabeth A.; Fawcett, Gloria L.; Cheverud, James M.

2011-01-01

34

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

PubMed

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

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

2011-10-26

35

The study of eQTL variations by RNA-seq: from SNPs to phenotypes.  

PubMed

Common DNA variants alter the expression levels and patterns of many human genes. Loci responsible for this genetic control are known as expression quantitative trait loci (eQTLs). The resulting variation of gene expression across individuals has been postulated to be a determinant of phenotypic variation and susceptibility to complex disease. In the past, the application of expression microarray and genetic variation data to study populations enabled the rapid identification of eQTLs in model organisms and humans. Now, a new technology promises to revolutionize the field. Massively parallel RNA sequencing (RNA-seq) provides unprecedented resolution, allowing us to accurately monitor not only the expression output of each genomic locus but also reconstruct and quantify alternatively spliced transcripts. RNA-seq also provides new insights into the regulatory mechanisms underlying eQTLs. Here, we discuss the major advances introduced by RNA-seq and summarize current progress towards understanding the role of eQTLs in determining human phenotypic diversity. PMID:21122937

Majewski, Jacek; Pastinen, Tomi

2010-11-29

36

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.

37

Analysis of copy number variation using quantitative interspecies competitive PCR  

Microsoft Academic Search

Over recent years small submicroscopic DNA copy- number variants (CNVs) have been highlighted as an important source of variation in the human genome, human phenotypic diversity and disease suscep- tibility. Consequently, there is a pressing need for the development of methods that allow the efficient, accurate and cheap measurement of genomic copy number polymorphisms in clinical cohorts. We have developed

Nigel M. Williams; Hywel Williams; Elisa Majounie; Nadine Norton; Beate Glaser; Huw R. Morris; Michael J. Owen; Michael C. O'Donovan

2008-01-01

38

The Loci of repeated evolution: a catalog of genetic hotspots of phenotypic variation.  

PubMed

What is the nature of the genetic changes underlying phenotypic evolution? We have catalogued 1008 alleles described in the literature that cause phenotypic differences among animals, plants, and yeasts. Surprisingly, evolution of similar traits in distinct lineages often involves mutations in the same gene ("gene reuse"). This compilation yields three important qualitative implications about repeated evolution. First, the apparent evolution of similar traits by gene reuse can be traced back to two alternatives, either several independent causative mutations or a single original mutational event followed by sorting processes. Second, hotspots of evolution-defined as the repeated occurrence of de novo mutations at orthologous loci and causing similar phenotypic variation-are omnipresent in the literature with more than 100 examples covering various levels of analysis, including numerous gain-of-function events. Finally, several alleles of large effect have been shown to result from the aggregation of multiple small-effect mutations at the same hotspot locus, thus reconciling micromutationist theories of adaptation with the empirical observation of large-effect variants. Although data heterogeneity and experimental biases prevented us from extracting quantitative trends, our synthesis highlights the existence of genetic paths of least resistance leading to viable evolutionary change. PMID:23617905

Martin, Arnaud; Orgogozo, Virginie

2013-03-21

39

Genic and nongenic contributions to natural variation of quantitative traits in maize  

PubMed Central

The complex genomes of many economically important crops present tremendous challenges to understand the genetic control of many quantitative traits with great importance in crop production, adaptation, and evolution. Advances in genomic technology need to be integrated with strategic genetic design and novel perspectives to break new ground. Complementary to individual-gene–targeted research, which remains challenging, a global assessment of the genomic distribution of trait-associated SNPs (TASs) discovered from genome scans of quantitative traits can provide insights into the genetic architecture and contribute to the design of future studies. Here we report the first systematic tabulation of the relative contribution of different genomic regions to quantitative trait variation in maize. We found that TASs were enriched in the nongenic regions, particularly within a 5-kb window upstream of genes, which highlights the importance of polymorphisms regulating gene expression in shaping the natural variation. Consistent with these findings, TASs collectively explained 44%–59% of the total phenotypic variation across maize quantitative traits, and on average, 79% of the explained variation could be attributed to TASs located in genes or within 5 kb upstream of genes, which together comprise only 13% of the genome. Our findings suggest that efficient, cost-effective genome-wide association studies (GWAS) in species with complex genomes can focus on genic and promoter regions.

Li, Xianran; Zhu, Chengsong; Yeh, Cheng-Ting; Wu, Wei; Takacs, Elizabeth M.; Petsch, Katherine A.; Tian, Feng; Bai, Guihua; Buckler, Edward S.; Muehlbauer, Gary J.; Timmermans, Marja C.P.; Scanlon, Michael J.; Schnable, Patrick S.; Yu, Jianming

2012-01-01

40

Efficient quantitative morphological phenotyping of genetically altered organisms using stereology  

Microsoft Academic Search

Genetically modified organisms present the challenge of quantifying structures and functions in organs, tissues and cells.\\u000a Morphological investigation is greatly facilitated by taking sections in MRI, CAT scanning, histological preparations or EM,\\u000a and powerful unbiased quantitative tools called stereology can use these sections in a sampling based approach to measure\\u000a volume, number surface and length. Stereological tools have become methods

John Milton Lucocq

2007-01-01

41

From phenotypic to molecular polymorphisms involved in naturally occurring variation of plant development.  

PubMed

An enormous amount of naturally occurring genetic variation affecting development is found within wild and domesticated plant species. This diversity is presumably involved in plant adaptation to different natural environments or in human preferences. In addition, such intraspecific variation provides the basis for the evolution of plant development at larger evolutionary scales. Natural phenotypic differences are now amenable to genetic dissection up to the identification of causal DNA polymorphisms. Here we describe 30 genes and their functional nucleotide polymorphisms currently found as underlying allelic variation accounting for plant intraspecific developmental diversity. These studies provide molecular and cellular mechanisms that determine natural variation for quantitative and qualitative traits such as: fruit and seed morphology, colour and composition; flowering time; seedling emergence; plant architecture and inflorescence or flower morphology. Besides, analyses of flowering time variation within several distant species allow molecular comparisons between species, which are detecting homologous genes with partly different functions and unrelated genes with analogous functions. Thus, considerable gene function differences are being revealed also among species. Inspection of a catalogue of intraspecific nucleotide functional polymorphisms shows that transcriptional regulators are the main class of genes involved. Furthermore, barely more than half of the polymorphisms described are located in coding regions and affect protein structure, while the rest are regulatory changes altering gene expression. These limited analyses of intraspecific developmental variation support Doebley and Lukens's proposition (1998) that modifications in cis -regulatory regions of transcriptional regulators represent a predominant mode for the evolution of novel forms, but await more detailed studies in wild plant species. PMID:16096977

Alonso-Blanco, Carlos; Mendez-Vigo, Belén; Koornneef, Maarten

2005-01-01

42

EVALUATING QUANTITATIVE VARIATION IN THE GENOME OF ZEA MAYS  

Microsoft Academic Search

Genomic diversity within the species Zea mays has been examined by measur- ing the variation in the repetitive component of the nuclear genome among North American inbred lines and varieties. This was done by preparing a set of clones of repetitive maize sequences that differ in function, molecular arrange- ment and multiplicity and then using these as probes for quantitative

CAROL J. RIVIN; CHRISTOPHER A. CULLIS; VIRGINIA WALBOT

1986-01-01

43

Sources of variation in quantitative computed tomography of the lung.  

PubMed

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

Coxson, Harvey O

2013-09-01

44

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

45

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

PubMed Central

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

2013-01-01

46

Phenotypic variations of orpk mutation and chromosomal localization of modifiers influencing kidney phenotype  

Microsoft Academic Search

The Oak Ridge polycystic kidney (orpk) mutant mouse model resulted from a transgene insertion into the Tg737 gene and exhibits a pleiotropic syndrome with lesions in the kidney, liver, and pancreas. We found marked differences in the phenotypic expression of the orpk mutation when bred on different genetic backgrounds. In the FVB\\/N background, the phenotype is very severe for kidney,

C Sommardahl; M Cottrell; J E Wilkinson; R P Woychik; D K Johnson

2001-01-01

47

Multiple-trait quantitative trait locus mapping with incomplete phenotypic data  

Microsoft Academic Search

BACKGROUND: Conventional multiple-trait quantitative trait locus (QTL) mapping methods must discard cases (individuals) with incomplete phenotypic data, thereby sacrificing other phenotypic and genotypic information contained in the discarded cases. Under standard assumptions about the missing-data mechanism, it is possible to exploit these cases. RESULTS: We present an expectation-maximization (EM) algorithm, derived for recombinant inbred and F2 genetic models but extensible

Zhigang Guo; James C Nelson

2008-01-01

48

Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes  

Microsoft Academic Search

Extensive studies are currently being performed to associate disease susceptibility with one form of genetic variation, namely, single-nucleotide polymorphisms (SNPs). In recent years, another type of common genetic variation has been characterized, namely, structural variation, including copy number variants (CNVs). To determine the overall contribution of CNVs to complex phenotypes, we have performed association analyses of expression levels of 14,925

Barbara E. Stranger; Matthew S. Forrest; Mark Dunning; Catherine E. Ingle; Claude Beazley; Natalie Thorne; Richard Redon; Christine P. Bird; Anna de Grassi; Charles Lee; Chris Tyler-Smith; Nigel Carter; Stephen W. Scherer; Simon Tavaré; Panagiotis Deloukas; Matthew E. Hurles; Emmanouil T. Dermitzakis

2007-01-01

49

Epigenetic Programming of Phenotypic Variations in Reproductive Strategies in the Rat Through Maternal Care  

Microsoft Academic Search

Studies across multiple organisms reveal considerable phenotypic variation in reproductive tac- tics. In some species, this variation is associated with maternal effects in which variation in maternal investment results in stable individual differences in reproductive function. Recent studies with the rat suggest that maternal effects can alter the function of neuroendocrine sys- tems associated with female sexual behaviour as well

N. M. Cameron; D. Shahrokh; A. Del Corpo; S. K. Dhir; M. Szyf; F. A. Champagne; M. J. Meaney

2008-01-01

50

Phenotypic Variation in FAM83H-associated Amelogenesis Imperfecta  

PubMed Central

FAM83H gene mutations are associated with autosomal-dominant hypocalcified amelogenesis imperfecta (ADHCAI), which is typically characterized by enamel having normal thickness and a markedly decreased mineral content. This study tested the hypothesis that there are phenotype and genotype associations in families with FAM83H-associated ADHCAI. Seven families segregating ADHCAI (147 individuals) were evaluated. Phenotyping included clinical, radiographic, histological, and biochemical studies, and genotyping was by mutational analysis. Multiple novel FAM83H mutations were identified, including two 2-bp-deletion mutations, the first non-nonsense mutations identified. Craniofacial deviation from normal was more prevalent in the affected individuals. Affected individuals having truncating FAMH3H mutations of 677 or fewer amino acids presented a generalized ADHCAI phenotype, while those having mutations capable of producing a protein of at least 694 amino acids had a unique and previously unreported phenotype affecting primarily the cervical enamel. This investigation shows that unique phenotypes are associated with specific FAM83H mutations.

Wright, J.T.; Frazier-Bowers, S.; Simmons, D.; Alexander, K.; Crawford, P.; Han, S.T.; Hart, P.S.; Hart, T.C.

2009-01-01

51

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans  

Microsoft Academic Search

OBJECTIVE:To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM).DESIGN:An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach.SUBJECTS:Sib-pairs affected with T2DM from the Africa America

G Chen; A A Adeyemo; T Johnson; J Zhou; A Amoah; S Owusu; J Acheampong; K Agyenim-Boateng; B A Eghan; J Oli; G Okafor; F Abbiyesuku; G M Dunston; Y Chen; F Collins; C Rotimi

2005-01-01

52

From Genotype to Phenotype: Systems Biology Meets Natural Variation  

PubMed Central

The promise that came with genome sequencing was that we would soon know what genes do, particularly genes involved in human diseases and those of importance to agriculture. 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.

Benfey, Philip N.; Mitchell-Olds, Thomas

2009-01-01

53

Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons  

Microsoft Academic Search

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

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

2010-01-01

54

Cerebral asymmetry: a quantitative, multifactorial, and plastic brain phenotype.  

PubMed

The longitudinal fissure separates the human brain into two hemispheres that remain connected through the corpus callosum. The left and the right halves of the brain resemble each other, and almost every structure present in one side has an equivalent structure in the other. Despite this exceptional correspondence, the two hemispheres also display important anatomical differences and there is marked lateralization of certain cognitive and motor functions such as language and handedness. However, the mechanisms that underlie the establishment of these hemispheric specializations, as well as their physiological and behavioral implications, remain largely unknown. Thanks to recent advances in neuroimaging, a series of studies documenting variation in symmetry and asymmetry as a function of age, gender, brain region, and pathological state, have been published in the past decade. Here, we review evidence of normal and atypical cerebral asymmetry, and the factors that influence it at the macrostructural level. Given the prominent role that cerebral asymmetry plays in the organization of the brain, and its possible implication in neurodevelopmental and psychiatric conditions, further research in this area is anticipated. PMID:22856374

Rentería, Miguel E

2012-06-01

55

Contrasting patterns of morphological and physiological differentiation across insular environments: phenotypic variation and heritability of light-related traits in Olea europaea.  

PubMed

Phenotypic variation of traits can reflect the ability of plants to adjust to particular environments, but how much of this variation is heritable is not frequently analyzed in natural populations. In the present paper, we investigated the patterns of phenotypic expression in light-related leaf traits of Olea europaea subsp. guanchica, a woody sclerophyllous species endemic to the Canary Islands. We explored phenotypic differentiation and heritable variation across several island populations differing in light environment. A suite of morpho-functional (leaf size, SLA and leaf angle) and physiological (pigment pools: Chl a/b ratio, xantophyll cycle and ?-carotene) traits was measured in six populations on three islands. In addition, we estimated heritabilities for these traits following Ritland's method. Variation in morpho-functional, but not in physiological, traits was observed across the islands and was significantly related to the amount of diffuse light experienced by each population. In addition, significant heritabilities were found for morpho-functional traits, whereas expression of similar phenotypes among populations was accompanied by a lack of heritable variation in physiological traits. Most recently established populations did not exhibit lower heritabilities in quantitative traits than older populations, and apparently displayed congruent phenotypes under the local conditions. Our results strongly support the idea that different types of traits show contrasted levels of genetic and phenotypic variation in populations experiencing marked environmental differences. PMID:20532918

García-Verdugo, C; Méndez, M; Velázquez-Rosas, N; Balaguer, L

2010-06-09

56

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

PubMed Central

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

Fournier-Level, Alexandre; Le Cunff, Loic; Gomez, Camila; Doligez, Agnes; Ageorges, Agnes; Roux, Catherine; Bertrand, Yves; Souquet, Jean-Marc; Cheynier, Veronique; This, Patrice

2009-01-01

57

Human olfaction: from genomic variation to phenotypic diversity  

Microsoft Academic Search

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

Yehudit Hasin-Brumshtein; Doron Lancet; Tsviya Olender

2009-01-01

58

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

59

Phenotypic variations of orpk mutation and chromosomal localization of modifiers influencing kidney phenotype.  

PubMed

The Oak Ridge polycystic kidney (orpk) mutant mouse model resulted from a transgene insertion into the Tg737 gene and exhibits a pleiotropic syndrome with lesions in the kidney, liver, and pancreas. We found marked differences in the phenotypic expression of the orpk mutation when bred on different genetic backgrounds. In the FVB/N background, the phenotype is very severe for kidney, pancreas, and liver lesions. To evaluate better how genetic background might influence the expressivity of the orpk phenotype, we bred the transgene into the C3HeB/FeJLe (C3H) genetic background. We performed a genome-wide scan using backcross and intercross populations with more than 150 markers to map the chromosomal location of the modifier genes that differ in the FVB/N and C3H genetic backgrounds that affect the severity of kidney disease in the orpk mouse. Low-resolution interval mapping was performed using the Map Manager QTb program, with the interval explaining a significant portion of the variance being the distal end of chromosome 4. PMID:11773599

Sommardahl, C; Cottrell, M; Wilkinson, J E; Woychik, R P; Johnson, D K

2001-12-21

60

Quantitative trait loci responsible for variation in sexually dimorphic traits in Drosophila melanogaster.  

PubMed

To understand the mechanisms of morphological evolution and species divergence, it is essential to elucidate the genetic basis of variation in natural populations. Sexually dimorphic characters, which evolve rapidly both within and among species, present attractive models for addressing these questions. In this report, we map quantitative trait loci (QTL) responsible for variation in sexually dimorphic traits (abdominal pigmentation and the number of ventral abdominal bristles and sex comb teeth) in a natural population of Drosophila melanogaster. To capture the pattern of genetic variation present in the wild, a panel of recombinant inbred lines was created from two heterozygous flies taken directly from nature. High-resolution mapping was made possible by cytological markers at the average density of one per 2 cM. We have used a new Bayesian algorithm that allows QTL mapping based on all markers simultaneously. With this approach, we were able to detect small-effect QTL that were not evident in single-marker analyses. Our results show that at least for some sexually dimorphic traits, a small number of QTL account for the majority of genetic variation. The three strongest QTL account for >60% of variation in the number of ventral abdominal bristles. Strikingly, a single QTL accounts for almost 60% of variation in female abdominal pigmentation. This QTL maps to the chromosomal region that Robertson et al. have found to affect female abdominal pigmentation in other populations of D. melanogaster. Using quantitative complementation tests, we demonstrate that this QTL is allelic to the bric a brac gene, whose expression has previously been shown to correlate with interspecific differences in pigmentation. Multiple bab alleles that confer distinct phenotypes appear to segregate in natural populations at appreciable frequencies, suggesting that intraspecific and interspecific variation in abdominal pigmentation may share a similar genetic basis. PMID:12618413

Kopp, Artyom; Graze, Rita M; Xu, Shizhong; Carroll, Sean B; Nuzhdin, Sergey V

2003-02-01

61

Patterns of Phenotypic Variation in a Germplasm Collection of Carthamus tinctorius L. from the Middle East  

Microsoft Academic Search

Phenotypic diversity was assessed for quantitative and qualitative traits in a salt-tolerant subset of the international safflower\\u000a (Carthamus tinctorius L.) germplasm collection originating from 11 countries in three regions (Central Asia, Southwest Asia and Africa) of the\\u000a Middle East. Phenotypically, the germplasm, among and within regions, was highly variable, especially for rosette- and yield-related\\u000a traits. Frequency of desirable variants of

A. A. Jaradat; M. Shahid

2006-01-01

62

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

63

Molecular ABO phenotyping in cynomolgus macaques using real-time quantitative PCR.  

PubMed

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 polymerase chain reaction. 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 exon 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 this study, that assumes the absence of the O allele, suggests the possibility of some mechanism preventing the expression of the A and B transferases. PMID:22861170

Premasuthan, A; Ng, J; Kanthaswamy, S; Trask, J S; Houghton, P; Farkas, T; Sestak, K; Smith, D G

2012-08-03

64

Rapid plant invasion in distinct climates involves different sources of phenotypic variation.  

PubMed

When exotic species spread over novel environments, their phenotype will depend on a combination of different processes, including phenotypic plasticity (PP), local adaptation (LA), environmental maternal effects (EME) and genetic drift (GD). Few attempts have been made to simultaneously address the importance of those processes in plant invasion. The present study uses the well-documented invasion history of Senecio inaequidens (Asteraceae) in southern France, where it was introduced at a single wool-processing site. It gradually invaded the Mediterranean coast and the Pyrenean Mountains, which have noticeably different climates. We used seeds from Pyrenean and Mediterranean populations, as well as populations from the first introduction area, to explore the phenotypic variation related to climatic variation. A reciprocal sowing experiment was performed with gardens under Mediterranean and Pyrenean climates. We analyzed climatic phenotypic variation in germination, growth, reproduction, leaf physiology and survival. Genetic structure in the studied invasion area was characterized using AFLP. We found consistent genetic differentiation in growth traits but no home-site advantage, so weak support for LA to climate. In contrast, genetic differentiation showed a relationship with colonization history. PP in response to climate was observed for most traits, and it played an important role in leaf trait variation. EME mediated by seed mass influenced all but leaf traits in a Pyrenean climate. Heavier, earlier-germinating seeds produced larger individuals that produced more flower heads throughout the growing season. However, in the Mediterranean garden, seed mass only influenced the germination rate. The results show that phenotypic variation in response to climate depends on various ecological and evolutionary processes associated with geographical zone and life history traits. Seeing the relative importance of EME and GD, we argue that a "local adaptation vs. phenotypic plasticity" approach is therefore not sufficient to fully understand what shapes phenotypic variation and genetic architecture of invasive populations. PMID:23383251

Monty, Arnaud; Bizoux, Jean-Philippe; Escarré, José; Mahy, Grégory

2013-01-30

65

Rapid Plant Invasion in Distinct Climates Involves Different Sources of Phenotypic Variation  

PubMed Central

When exotic species spread over novel environments, their phenotype will depend on a combination of different processes, including phenotypic plasticity (PP), local adaptation (LA), environmental maternal effects (EME) and genetic drift (GD). Few attempts have been made to simultaneously address the importance of those processes in plant invasion. The present study uses the well-documented invasion history of Senecio inaequidens (Asteraceae) in southern France, where it was introduced at a single wool-processing site. It gradually invaded the Mediterranean coast and the Pyrenean Mountains, which have noticeably different climates. We used seeds from Pyrenean and Mediterranean populations, as well as populations from the first introduction area, to explore the phenotypic variation related to climatic variation. A reciprocal sowing experiment was performed with gardens under Mediterranean and Pyrenean climates. We analyzed climatic phenotypic variation in germination, growth, reproduction, leaf physiology and survival. Genetic structure in the studied invasion area was characterized using AFLP. We found consistent genetic differentiation in growth traits but no home-site advantage, so weak support for LA to climate. In contrast, genetic differentiation showed a relationship with colonization history. PP in response to climate was observed for most traits, and it played an important role in leaf trait variation. EME mediated by seed mass influenced all but leaf traits in a Pyrenean climate. Heavier, earlier-germinating seeds produced larger individuals that produced more flower heads throughout the growing season. However, in the Mediterranean garden, seed mass only influenced the germination rate. The results show that phenotypic variation in response to climate depends on various ecological and evolutionary processes associated with geographical zone and life history traits. Seeing the relative importance of EME and GD, we argue that a “local adaptation vs. phenotypic plasticity” approach is therefore not sufficient to fully understand what shapes phenotypic variation and genetic architecture of invasive populations.

Monty, Arnaud; Bizoux, Jean-Philippe; Escarre, Jose; Mahy, Gregory

2013-01-01

66

Quantitative trait loci in Drosophila  

Microsoft Academic Search

Phenotypic variation for quantitative traits results from the simultaneous segregation of alleles at multiple quantitative trait loci. Understanding the genetic architecture of quantitative traits begins with mapping quantitative trait loci to broad genomic regions and ends with the molecular definition of quantitative trait loci alleles. This has been accomplished for some quantitative trait loci in Drosophila. Drosophila quantitative trait loci

Trudy F. C. Mackay

2001-01-01

67

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

68

Phenotypic variation for adhesive tenacity in the barnacle Balanus amphitrite  

Microsoft Academic Search

Silicone fouling-release coatings represent a non-toxic alternative to biocide-containing ship hull paints. These coatings allow fouling organisms to attach to the hull surface, but prevent firm adhesion. Adhesive tenacity to fouling-release materials varies both among and within species. We quantified broad-sense genetic and environmental sources of intraspecific variation in tenacity to two silicone substrata, for the barnacle Balanus amphitrite. For

Eric R. Holm; Christopher J. Kavanagh; Beatriz Orihuela; Daniel Rittschof

2009-01-01

69

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

PubMed

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. PMID:18544662

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

2008-06-10

70

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

71

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

Microsoft Academic Search

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

R. Ortiz; S. Madsen; D. Vuylsteke

1998-01-01

72

Selection on quantitative colour variation in Centaurea cyanus: the role of the pollinator's visual system.  

PubMed

Even though the importance of selection for trait evolution is well established, we still lack a functional understanding of the mechanisms underlying phenotypic selection. Because animals necessarily use their sensory system to perceive phenotypic traits, the model of sensory bias assumes that sensory systems are the main determinant of signal evolution. Yet, it has remained poorly known how sensory systems contribute to shaping the fitness surface of selected individuals. In a greenhouse experiment, we quantified the strength and direction of selection on floral coloration in a population of cornflowers exposed to bumblebees as unique pollinators during 4 days. We detected significant selection on the chromatic and achromatic (brightness) components of floral coloration. We then studied whether these patterns of selection are explicable by accounting for the visual system of the pollinators. Using data on bumblebee colour vision, we first showed that bumblebees should discriminate among quantitative colour variants. The observed selection was then compared to the selection predicted by psychophysical models of bumblebee colour vision. The achromatic but not the chromatic channel of the bumblebee's visual system could explain the observed pattern of selection. These results highlight that (i) pollinators can select quantitative variation in floral coloration and could thus account for a gradual evolution of flower coloration, and (ii) stimulation of the visual system represents, at least partly, a functional mechanism potentially explaining pollinators' selection on floral colour variants. PMID:24070120

Renoult, J P; Thomann, M; Schaefer, H M; Cheptou, P-O

2013-09-24

73

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

74

Integrating environmental variation, predation pressure, phenotypic plasticity and locomotor performance.  

PubMed

The Wujiang River, a tributary of the Three Gorges Reservoir, has many dams along its length. These dams alter the river's natural habitat and produce various flow regimes and degrees of predator stress. To test whether the swimming performance and external body shape of pale chub (Zacco platypus) have changed as a result of alterations in the flow regime and predator conditions, we measured the steady (U crit) and unsteady (fast-start) swimming performances and morphological characteristics of fish collected from different sites along the Wujiang River. We also calculated the maximum respiratory capacity and cost of transport (COT). We demonstrated significant differences in swimming performance and morphological traits among the sampling sites. Steady swimming performance was positively correlated with water velocity and negatively correlated with the abundance of predators, whereas unsteady swimming performance was negatively correlated with water velocity. The body shape was significantly correlated with both swimming performance and ecological parameters. These findings suggested that selection pressure on swimming performance results in a higher U crit and a more streamlined body shape in fast-flow and (or) in habitats with low predator stress and subsequently results in a lower COT. These characteristics were accompanied by a poorer fast-start performance than that of the fish from the slow-flow and (or) high-predator habitats. The divergence in U crit may also be due in part to variation in respiratory capacity. PMID:23463244

Fu, Shi-Jian; Cao, Zhen-Dong; Yan, Guan-Jie; Fu, Cheng; Pang, Xu

2013-03-06

75

The quantitative genetics of floral trait variation in Lobelia: potential constraints on adaptive evolution.  

PubMed

Although pollinator-mediated natural selection has been measured on many floral traits and in many species, the extent to which selection is constrained from producing optimal floral phenotypes is less frequently studied. In particular, negative correlations between flower size and flower number are hypothesized to be a major constraint on the evolution of floral displays, yet few empirical studies have documented such a trade-off. To determine the potential for genetic constraints on the adaptive evolution of floral displays, I estimated the quantitative genetic basis of floral trait variation in two populations of Lobelia siphilitica. Restricted maximum likelihood (REML) analyses of greenhouse-grown half-sib families were used to estimate genetic variances and covariances for flower number and six measures of flower size. There was significant genetic variation for all seven floral traits in both populations. Flower number was negatively genetically correlated with four measures of flower size in one population and three measures in the other. When the genetic variance-covariance matrices were combined with field estimates of phenotypic selection gradients, the predicted multivariate evolutionary response was less than or opposite in sign to the selection gradient for flower number and five of six measures of flower size, suggesting genetic constraints on the evolution of these traits. More generally, my results indicate that the adaptive evolution of floral displays can be constrained by trade-offs between flower size and number, as has been assumed by many theoretical models of floral evolution. PMID:15154549

Caruso, Christina M

2004-04-01

76

The molecular basis of quantitative variation in foliar secondary metabolites in Eucalyptus globulus.  

PubMed

Eucalyptus is characterized by high foliar concentrations of plant secondary metabolites with marked qualitative and quantitative variation within a single species. Secondary metabolites in eucalypts are important mediators of a diverse community of herbivores. We used a candidate gene approach to investigate genetic associations between 195 single nucleotide polymorphisms (SNPs) from 24 candidate genes and 33 traits related to secondary metabolites in the Tasmanian Blue Gum (Eucalyptus globulus). We discovered 37 significant associations (false discovery rate (FDR) Q < 0.05) across 11 candidate genes and 19 traits. The effects of SNPs on phenotypic variation were within the expected range (0.018 < r(2) < 0.061) for forest trees. Whereas most marker effects were nonadditive, two alleles from two consecutive genes in the methylerythritol phosphate pathway (MEP) showed additive effects. This study successfully links allelic variants to ecologically important phenotypes which can have a large impact on the entire community. It is one of very few studies to identify the genetic variants of a foundation tree that influences ecosystem function. PMID:21609332

Külheim, Carsten; Yeoh, Suat Hui; Wallis, Ian R; Laffan, Shawn; Moran, Gavin F; Foley, William J

2011-05-24

77

Phenotypic plasticity in response to fine-grained environmental variation in predation  

Microsoft Academic Search

Summary 1. In nature, organisms experience environmental variability at coarse-grained (inter-generational) and fine-grained (intra-generational) scales and a common response to environmental variation is phenotypic plasticity. The emphasis of most empirical work on plasticity has been on examining coarse-grained variation with the goal of understanding the costs and benefits of plastic responses in response to a particular environment. 2. In this

Nancy M. Schoeppner; Rick A. Relyea

2009-01-01

78

PhenoMiner: quantitative phenotype curation at the rat genome database.  

PubMed

The Rat Genome Database (RGD) is the premier repository of rat genomic and genetic data and currently houses >40 000 rat gene records as well as human and mouse orthologs, >2000 rat and 1900 human quantitative trait loci (QTLs) records and >2900 rat strain records. Biological information curated for these data objects includes disease associations, phenotypes, pathways, molecular functions, biological processes and cellular components. Recently, a project was initiated at RGD to incorporate quantitative phenotype data for rat strains, in addition to the currently existing qualitative phenotype data for rat strains, QTLs and genes. A specialized curation tool was designed to generate manual annotations with up to six different ontologies/vocabularies used simultaneously to describe a single experimental value from the literature. Concurrently, three of those ontologies needed extensive addition of new terms to move the curation forward. The curation interface development, as well as ontology development, was an ongoing process during the early stages of the PhenoMiner curation project. Database URL: http://rgd.mcw.edu. PMID:23603846

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

2013-04-19

79

PhenoMiner: quantitative phenotype curation at the rat genome database  

PubMed Central

The Rat Genome Database (RGD) is the premier repository of rat genomic and genetic data and currently houses >40 000 rat gene records as well as human and mouse orthologs, >2000 rat and 1900 human quantitative trait loci (QTLs) records and >2900 rat strain records. Biological information curated for these data objects includes disease associations, phenotypes, pathways, molecular functions, biological processes and cellular components. Recently, a project was initiated at RGD to incorporate quantitative phenotype data for rat strains, in addition to the currently existing qualitative phenotype data for rat strains, QTLs and genes. A specialized curation tool was designed to generate manual annotations with up to six different ontologies/vocabularies used simultaneously to describe a single experimental value from the literature. Concurrently, three of those ontologies needed extensive addition of new terms to move the curation forward. The curation interface development, as well as ontology development, was an ongoing process during the early stages of the PhenoMiner curation project. Database URL: http://rgd.mcw.edu

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

2013-01-01

80

Phenotypic variations in a family with retinal dystrophy as result of different mutations in the ABCRgene  

Microsoft Academic Search

AIMSTo describe two phenotypic variations of autosomal recessive retinal dystrophy occurring in a consanguineous family in a pseudodominant pattern, resulting from mutations in the ATP binding cassette transporter (ABCR) gene.METHODSPatients of this family underwent an extensive ophthalmic evaluation, including fundus photography, fluorescein angiography, and electroretinography (ERG). Genetic analysis comprised sequence analysis of the retina specific ABCR gene.RESULTSFive patients presented with

B Jeroen Klevering; Marc van Driel; Dorien J R van de Pol; Alfred J L G Pinckers; Frans P M Cremers; Carel B Hoyng

1999-01-01

81

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

Microsoft Academic Search

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

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

2007-01-01

82

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

Microsoft Academic Search

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

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

2000-01-01

83

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

84

The vigour of glasshouse roses. Scion rootstock relationships, effects of phenotypic & genotypic variation  

Microsoft Academic Search

Glasshouse roses commonly are combination plants, consisting of a scion variety and a rootstock of different genotypes. In this study, various environmental and genotypic factors have been investigated that influence the vigour of rootstocks and scion varieties, separately and in graft combination.In a field crop of Edelcanina (selections of R.canina L.) rootstock plants, significant phenotypic variation occurred for all plant

Vries de D. P

1993-01-01

85

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

86

Relative contribution of additive, dominance, and imprinting effects to phenotypic variation in body size and growth between divergent selection lines of mice.  

PubMed

Epigenetic effects attributed to genomic imprinting are increasingly recognized as an important source of variation in quantitative traits. However, little is known about their relative contribution to phenotypic variation compared to those of additive and dominance effects, and almost nothing about their role in phenotypic evolution. Here we address these questions by investigating the relative contribution of additive, dominance, and imprinting effects of quantitative trait loci (QTL) to variation in "early" and "late" body weight in an intercross of mice selected for divergent adult body weight. We identified 18 loci on 13 chromosomes; additive effects accounted for most of the phenotypic variation throughout development, and imprinting effects were always small. Genetic effects on early weight showed more dominance, less additive, and, surprisingly, less imprinting variation than that of late weight. The predominance of additivity of QTL effects on body weight follows the expectation that additive effects account for the evolutionary divergence between selection lines. We hypothesize that the appearance of more imprinting effects on late body weight may be a consequence of divergent selection on adult body weight, which may have indirectly selected for alleles showing partial imprinting effects due to their associated additive effects, highlighting a potential role of genomic imprinting in the response to selection. PMID:19187253

Hager, Reinmar; Cheverud, James M; Wolf, Jason B

2008-02-02

87

Haploid vegetative mycelia of Armillaria gallica show among-cell-line variation for growth and phenotypic plasticity.  

PubMed

Vegetative mycelial cells of Armillaria are expected to have diploid nuclei. Cells from a single mycelium therefore would not be expected to differ from one another for ecologically relevant quantitative traits. We isolated two sets of basidiome cell lines (from spores and stipe cells) and one set of vegetative cell lines (from an attached rhizomorph) from a single contiguous Armillaria gallica mycelium. We isolated a second set of vegetative cell lines from the soil 20 cm from the above basidiome-rhizomorph complex. In all four sets of cell lines in situ DAPI-DNA measurements showed cells are haploid and quantitative-trait analyses of cell lines grown at different water potentials revealed high levels of among-cell-line genetic variation for both growth and phenotypic plasticity. Haploidy and the existence of ecologically relevant genetic variation within vegetative individuals are unexpected and mean that a process similar to evolutionary adaptation could take place within the soma of a genetic individual. We believe this is a key to understanding how large A. gallica mycelia survive exposure to variation in ecological conditions during lives that potentially span several tree (host) generations. PMID:16457347

Peabody, Robert B; Peabody, Diane Cope; Tyrrell, Maura Geens; Edenburn-MacQueen, Emily; Howdy, Richard P; Semelrath, Kevin M

88

Body Mass Index as a Phenotypic Expression of Adiposity: Quantitative Contribution of Muscularity in a Population-Based Sample  

PubMed Central

Objective Although widely applied as a phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI) is also acknowledged to reflect muscularity even though relevant studies directly measuring skeletal muscle (SM) mass are lacking. The current study aimed to fill this important gap by applying advanced imaging methods to test the hypothesis that, after controlling first for adiposity, SM mass is also a significant determinant of BMI in a population-based sample. Design Whole-body magnetic resonance imaging scans were completed in CARDIA Study subjects aged 33-45 years. Physical activity (PA) levels, alcohol intake, and adequacy of food intake were assessed by standardized questionnaires. Subjects 58 African-American (AA) and 78 Caucasian (C) men; 63 AA and 64 C women. Measurements Whole-body AT and SM volumes. Results AT was significantly predicted by not only BMI, but PA and alcohol intake with total model R2s of 0.68 (p<0.0001) for men and 0.89 (p<0.0001) for women. Men had more SM than AT at all levels of BMI while SM predominated in women at lower BMIs (C <26 kg/m2; AA <28 kg/m2). Both AT and SM contributed a similar proportion of between-subject variation in BMI in men. In contrast, AT contributed ~30% more than SM to the variation in BMI in women. Developed allometric models indicated SM associations with AT, PA, and race after adjusting for height. There was little association of age, lifestyle factors, or race with BMI after controlling for both AT and SM. Conclusion Variation in muscularity provides a mechanistic basis for the previously observed non-specificity of BMI as a phenotypic expression of adiposity. These quantitative observations have important implications when choosing adiposity measures in population and gene-search studies.

Heymsfield, Steven B.; Scherzer, Rebecca; Pietrobelli, Angelo; Lewis, Cora E.; Grunfeld, Carl

2010-01-01

89

Quantitative Expression of G6PD Activity of Different Phenotypes of G6PD and Haemoglobin in a Sudanese Population  

Microsoft Academic Search

597 unrelated persons, comprising of 401 males and 196 females, were investigated for glucose-6-phosphate dehydrogenase (G6PD) and haemoglobin phenotypes by starch gel electrophoresis. The levels of G6PD activity were assayed in order to study the quantitative expression of G6PD phenotypes and the influence of haemoglobin phenotypes on such expression. There was no significant difference in the levels of G6PD activity

A. P. W. Samuel; N. Saha; A. Omer; A. V. Hoffbrand

1981-01-01

90

Stressful environments induce novel phenotypic variation: hierarchical reaction norms for sperm performance of a pervasive invader  

PubMed Central

Genetic variation for phenotypic plasticity is ubiquitous and important. However, the scale of such variation including the relative variability present in reaction norms among different hierarchies of biological organization (e.g., individuals, populations, and closely related species) is unknown. Complicating interpretation is a trade-off in environmental scale. As plasticity can only be inferred over the range of environments tested, experiments focusing on fine tuned responses to normal or benign conditions may miss cryptic phenotypic variation expressed under novel or stressful environments. Here, we sought to discern the presence and shape of plasticity in the performance of brown trout sperm as a function of optimal to extremely stressful river pH, and demarcate if the reaction norm varies among genotypes. Our overarching goal was to determine if deteriorating environmental quality increases expressed variation among individuals. A more applied aim was to ascertain whether maintaining sperm performance over a wide pH range could help explain how brown trout are able to invade diverse river systems when transplanted outside of their native range. Individuals differed in their reaction norms of phenotypic expression of an important trait in response to environmental change. Cryptic variation was revealed under stressful conditions, evidenced through increasing among-individual variability. Importantly, data on population averages masked this variability in plasticity. In addition, canalized reaction norms in sperm swimming velocities of many individuals over a very large range in water chemistry may help explain why brown trout are able to colonize a wide variety of habitats.

Purchase, Craig F; Moreau, Darek T R

2012-01-01

91

Stressful environments induce novel phenotypic variation: hierarchical reaction norms for sperm performance of a pervasive invader.  

PubMed

Genetic variation for phenotypic plasticity is ubiquitous and important. However, the scale of such variation including the relative variability present in reaction norms among different hierarchies of biological organization (e.g., individuals, populations, and closely related species) is unknown. Complicating interpretation is a trade-off in environmental scale. As plasticity can only be inferred over the range of environments tested, experiments focusing on fine tuned responses to normal or benign conditions may miss cryptic phenotypic variation expressed under novel or stressful environments. Here, we sought to discern the presence and shape of plasticity in the performance of brown trout sperm as a function of optimal to extremely stressful river pH, and demarcate if the reaction norm varies among genotypes. Our overarching goal was to determine if deteriorating environmental quality increases expressed variation among individuals. A more applied aim was to ascertain whether maintaining sperm performance over a wide pH range could help explain how brown trout are able to invade diverse river systems when transplanted outside of their native range. Individuals differed in their reaction norms of phenotypic expression of an important trait in response to environmental change. Cryptic variation was revealed under stressful conditions, evidenced through increasing among-individual variability. Importantly, data on population averages masked this variability in plasticity. In addition, canalized reaction norms in sperm swimming velocities of many individuals over a very large range in water chemistry may help explain why brown trout are able to colonize a wide variety of habitats. PMID:23145341

Purchase, Craig F; Moreau, Darek T R

2012-09-13

92

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

2011-01-11

93

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

PubMed Central

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

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

2011-01-01

94

Region and site conditions affect phenotypic trait variation in five forest herbs  

NASA Astrophysics Data System (ADS)

Phenotypic plasticity is the ability of organisms to express different phenotypes under different environmental conditions. It may buffer individuals both against short-term environmental fluctuations and long-term effects of global change. A plastic behaviour in response to changes in the environment may be especially important in species with low migration rates and colonization capacities, such as in many forest plants in present-day fragmented landscapes. We compared the phenotypic trait variation (used as a proxy for the amount of phenotypic plasticity) of five forest herbs (Brachypodium sylvaticum, Circaea lutetiana, Impatiens noli-tangere, Sanicula europaea and Stachys sylvatica) between two regions in Germany that differ in their overall environmental conditions (Bremen in the northwest, Freiburg in the southwest; 5 species × 2 regions × 8-15 populations × 25-50 individuals). In addition, we measured light intensity and important soil parameters (soil pH, moisture, K, P and N) in all populations. We found consistent differences in trait variability between the two regions in several species. In Brachypodium and Stachys both vegetative and reproductive traits were more variable in Freiburg. Similarly, reproductive traits of Impatiens and Sanicula appeared to be more variable in Freiburg, while in both species at least one of the vegetative traits was more variable in Bremen. Mean local environmental conditions also affected trait variation; in most of the species both vegetative and reproductive traits were more variable in sites with higher nutrient contents and higher light availability. Across all traits and both regions, seed or fruit production was most variable. In summary, at least some of the studied forest herbs appear to respond strongly to large-scale environmental differences, showing a higher trait variability in the more southern region. Given the assumption that phenotypic trait variation is positively associated with phenotypic plasticity, we conclude that these populations may more easily respond to changes in the environment.

Lemke, Isgard Holle; Kolb, Annette; Diekmann, Martin Reemt

2012-02-01

95

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

96

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

2012-04-23

97

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

98

Domestication of Irvingia gabonensis : 3. Phenotypic variation of fruits andkernels in a Nigerian village  

Microsoft Academic Search

Domestication of Irvingia gabonensis, a fruit tree grown in agroforestry systems in West and Central Africa, offers considerable scope for enhancing the nutritional\\u000a and economic security of subsistence farmers in the region. Assessments of phenotypic variation in ten fruit, nut and kernel\\u000a traits were made on twenty-four ripe fruits from 100 Irvingia gabonensis trees in Ugwuaji village in southeast Nigeria,

P. O. Anegbeh; C. Usoro; V. Ukafor; Z. Tchoundjeu; R. R. B. Leakey; K. Schreckenberg

2003-01-01

99

Earlier migration timing, decreasing phenotypic variation, and biocomplexity in multiple salmonid species.  

PubMed

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. PMID:23326513

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

2013-01-10

100

A Pleiotropic Nonadditive Model of Variation in Quantitative Traits  

PubMed Central

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. These experiments suggest a leptokurtic distribution of effects with an intermediate correlation between effects on the trait and fitness. 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, in which the proportion of mutations with an effect on the trait is small, 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(4) to 10(6), and most of the variance for the metric trait in segregating populations is due to a small proportion of mutations (about 1% of the total number) with neutral or nearly neutral effects on fitness and intermediate effects on the trait (0.1-0.5?(P)). Much of the genetic variance is contributed by recessive or partially recessive mutants, but only a small proportion (about 10%) of the genetic variance is dominance variance. The amount of apparent selection on the trait itself generated by the model is very small. 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 viability, the heritability is about 0.1, independent of the population size.

Caballero, A.; Keightley, P. D.

1994-01-01

101

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

Technology Transfer Automated Retrieval System (TEKTRAN)

The choice of populations for quantitative genetics experiments impacts inferences about genetic architecture and prospective selection gains. Plant breeding and quantitative genetics studies are often conducted in one or a few among many possible biparental families. Trait genotypic variation withi...

102

Quantitative genetic basis of arterial phenotypes in the Brown Norway rat.  

PubMed

The Brown Norway (BN) rat presents several genetically determined arterial phenotypes of interest, i.e., ruptures of the internal elastic lamina (RIEL) in the abdominal aorta (AA), iliac (IAs), and renal arteries, aortic elastin deficit and higher frequency of persistent ductus arteriosus (PDA) than other strains. We investigated the genetic basis of these phenotypes. We established a backcross between BN and the LOU reference strain and performed a genome-wide scan on 104 males and 105 females with 193 microsatellite markers followed by linkage analysis. RIEL in AA and IAs showed highly significant linkage to a locus on chromosome 5 and suggestive linkage to a locus on chromosome 10, which is syntenic to one linked to a syndrome of thoracic aortic aneurysms with PDA in humans. In contrast, renal artery RIEL mapped to a chromosome 3 locus and thoracic aortic elastic content to two loci on chromosome 2. PDA was significantly linked to two different quantitative trait loci (QTL) on chromosomes 8 and 9. This is the first study in rats to identify genetic loci for PDA. We identified 21 candidate genes by functional relevance or integration of our mapping data with global expression analysis. Sequencing these genes identified 47 single nucleotide polymorphisms, but no functionally relevant amino acid changes. By expression analysis, myosin heavy chain 10, nonmuscle, in the chromosome 10 QTL, emerged as a candidate for RIEL in AA and IAs. Furthermore, production of a congenic line for the chromosome 5 QTL proved implication of this locus in RIEL formation. PMID:17356016

Kota, Lalitha; Osborne-Pellegrin, Mary; Schulz, Herbert; Behmoaras, Jacques; Coutard, Michèle; Gong, Maolian; Hübner, Norbert

2007-03-13

103

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

104

Multiple Disguises for the Same Party: The Concepts of Morphogenesis and Phenotypic Variations in Cryptococcus neoformans†  

PubMed Central

Although morphological transitions (such as hyphae and pseudohyphae formation) are a common feature among fungi, the encapsulated pathogenic yeast Cryptococcus neoformans is found during infection as blastoconidia. However, this fungus exhibits striking variations in cellular structure and size, which have important consequences during infection. This review will summarize the main aspects related with phenotypic and morphological variations in C. neoformans, which can be divided in three classes. Two of them are related to changes in the capsule, while the third one involves changes in the whole cell. The three morphological and phenotypic variations in C. neoformans can be classified as: (1) changes in capsule structure, (2) changes in capsule size, and (3) changes in the total size of the cell, which can be achieved by the formation of cryptococcal giant/titan cells or microforms. These changes have profound consequences on the interaction with the host, involving survival, phagocytosis escape and immune evasion and dissemination. This article will summarize the main features of these changes, and highlight their importance during the interaction with the host and how they contribute to the development of the disease.

Zaragoza, Oscar

2011-01-01

105

Variation and selection of quantitative traits in plant pathogens.  

PubMed

The first section presents the quantitative traits of pathogenicity that are most commonly measured by plant pathologists, how the expression of those traits is influenced by environmental factors, and why the traits must be taken into account for understanding pathogen evolution in agricultural systems. Particular attention is given to the shared genetic control of these traits by the host and the pathogen. Next, the review discusses how quantitative traits account for epidemic development and how they can be related to pathogen fitness. The main constraints that influence the evolution of quantitative traits in pathogen populations are detailed. Finally, possible directions for research on the management of pathogen virulence (as defined by evolutionists) and host quantitative resistance are presented. The review evaluates how the theoretical corpus developed by epidemiologists and evolutionists may apply to plant pathogens in the context of agriculture. The review also analyzes theoretical papers and compares the modeling hypotheses to the biological characteristics of plant pathogens. PMID:22702351

Lannou, Christian

2012-06-11

106

Female guppies agree to differ: phenotypic and genetic variation in mate-choice behavior and the consequences for sexual selection.  

PubMed

Variation among females in mate choice may influence evolution by sexual selection. The genetic basis of this variation is of interest because the elaboration of mating preferences requires additive genetic variation in these traits. Here we measure the repeatability and heritability of two components of female choosiness (responsiveness and discrimination) and of female preference functions for the multiple ornaments borne by male guppies (Poecilia reticulata). We show that there is significant repeatable variation in both components of choosiness and in some preference functions but not in others. There appear to be several male ornaments that females find uniformly attractive and others for which females differ in preference. One consequence is that there is no universally attractive male phenotype. Only responsiveness shows significant additive genetic variation. Variation in responsiveness appears to mask variation in discrimination and some preference functions and may be the most biologically relevant source of phenotypic and genetic variation in mate-choice behavior. To test the potential evolutionary importance of the phenotypic variation in mate choice that we report, we estimated the opportunity for and the intensity of sexual selection under models of mate choice that excluded and that incorporated individual female variation. We then compared these estimates with estimates based on measured mating success. Incorporating individual variation in mate choice generally did not predict the outcome of sexual selection any better than models that ignored such variation. PMID:11580024

Brooks, R; Endler, J A

2001-08-01

107

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

Microsoft Academic Search

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

J H Marden

2008-01-01

108

SSR-marker analysis of the intracultivar phenotypic variation discovered within 3 soybean cultivars.  

PubMed

Genetic variation within homogeneous gene pools in various crops is assumed to be very limited. One objective of this study was to use 144 simple sequence repeat (SSR) markers to determine if the single-plant lines selected at ultra-low plant density in honeycomb designs within the soybean cultivars Benning, Haskell, and Cook had unique SSR genetic fingerprints. Another objective was to investigate if the variation found was the result of residual genetic heterozygosity that could be detected in the original gene pool where selection initiated. Our results showed that the phenotypic variation for seed protein content and seed weight has a genotypic component identified by the SSR band variation. The 7 lines from Haskell had a total of 63 variant alleles, the 5 lines from Benning had 34 variant alleles, and the 7 lines from Cook had 34 variant alleles, therefore, possessing unique genetic fingerprints. Most of the intracultivar SSR band variation discovered was the result of residual heterozygosity in the initial plant selected to become the cultivar. More specifically, 82% of the SSR variant alleles were traced in the Benning Foundation seed source, 93% in the Haskell seed source, and 82% in the Cook seed source. The remaining variant bands (18% for Benning, 7% for Haskell, and 18% for Cook) could not be detected in the Foundation seed source and were likely the result of mutation or some other mechanism generating de novo variation. These results provide evidence that genetic variation among individual plants is present even in homogeneous gene pools and can be further utilized in breeding programs. PMID:22547666

Yates, Jennifer L; Boerma, H Roger; Fasoula, Vasilia A

2012-04-30

109

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

PubMed Central

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.

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

2002-01-01

110

Quantitative Trait Loci Underlying Gene Product Variation: A Novel Perspective for Analyzing Regulation of Genome Expression  

PubMed Central

A methodology to dissect the genetic architecture of quantitative variation of numerous gene products simultaneously is proposed. For each individual of a segregating progeny, proteins extracted from a given organ are separated using two-dimensional electrophoresis, and their amounts are estimated with a computer-assisted system for spot quantification. Provided a complete genetic map is available, statistical procedures allow determination of the number, effects and chromosomal locations of factors controlling the amounts of individual proteins. This approach was applied to anonymous proteins of etiolated coleoptiles of maize, in an F(2) progeny between two distant lines. The genetic map included both restriction fragment length polymorphism and protein markers. Minimum estimates of one to five unlinked regulatory factors were found for 42 of the 72 proteins analyzed, with a large diversity of effects. Dominance and epistasis interactions were involved in the control of 38% and 14% of the 72 proteins, respectively. Such a methodology might help understanding the architecture of regulatory networks and the possible adaptive or phenotypic significance of the polymorphism of the genes involved.

Damerval, C.; Maurice, A.; Josse, J. M.; de-Vienne, D.

1994-01-01

111

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

112

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

113

Quantitative mouse brain phenotyping based on single and multispectral MR protocols.  

PubMed

Sophisticated image analysis methods have been developed for the human brain, but such tools still need to be adapted and optimized for quantitative small animal imaging. We propose a framework for quantitative anatomical phenotyping in mouse models of neurological and psychiatric conditions. The framework encompasses an atlas space, image acquisition protocols, and software tools to register images into this space. We show that a suite of segmentation tools (Avants, Epstein et al., 2008) designed for human neuroimaging can be incorporated into a pipeline for segmenting mouse brain images acquired with multispectral magnetic resonance imaging (MR) protocols. We present a flexible approach for segmenting such hyperimages, optimizing registration, and identifying optimal combinations of image channels for particular structures. Brain imaging with T1, T2* and T2 contrasts yielded accuracy in the range of 83% for hippocampus and caudate putamen (Hc and CPu), but only 54% in white matter tracts, and 44% for the ventricles. The addition of diffusion tensor parameter images improved accuracy for large gray matter structures (by >5%), white matter (10%), and ventricles (15%). The use of Markov random field segmentation further improved overall accuracy in the C57BL/6 strain by 6%; so Dice coefficients for Hc and CPu reached 93%, for white matter 79%, for ventricles 68%, and for substantia nigra 80%. We demonstrate the segmentation pipeline for the widely used C57BL/6 strain, and two test strains (BXD29, APP/TTA). This approach appears promising for characterizing temporal changes in mouse models of human neurological and psychiatric conditions, and may provide anatomical constraints for other preclinical imaging, e.g. fMRI and molecular imaging. This is the first demonstration that multiple MR imaging modalities combined with multivariate segmentation methods lead to significant improvements in anatomical segmentation in the mouse brain. PMID:22836174

Badea, Alexandra; Gewalt, Sally; Avants, Brian B; Cook, James J; Johnson, G Allan

2012-07-23

114

Modular genetic architecture of floral morphology in Nicotiana: quantitative genetic and comparative phenotypic approaches to floral integration.  

PubMed

Animal-pollinated flowers are complex structures that may require a precise configuration of floral organs for proper function. As such, they represent an excellent system with which we can examine the role of phenotypic integration and modularity in morphological evolution. We use complementary quantitative genetic and comparative phenotypic approaches to examine correlations among floral characters in Nicotiana alata, N. forgetiana and their artificial fourth-generation hybrids. Flowers of both species share basic patterns of genetic and phenotypic correlations characterized by at least two integrated character suites that are relatively independent of each other and are not disrupted by four generations of recombination in hybrids. We conclude that these integrated character suites represent phenotypic modules that are the product of a modular genetic architecture. Intrafloral modularity may have been critical for rapid specialization of these species to different pollinators. PMID:20561132

Bissell, E K; Diggle, P K

2010-06-17

115

Databases of genomic variation and phenotypes: existing resources and future needs.  

PubMed

Massively parallel sequencing (MPS) has become an important tool for identifying medically significant variants in both research and the clinic. Accurate variation and genotype-phenotype databases are critical in our ability to make sense of the vast amount of information that MPS generates. The purpose of this review is to summarize the state of the art of variation and genotype-phenotype databases, how they can be used, and opportunities to improve these resources. Our working assumption is that the objective of the clinical genomicist is to identify highly penetrant variants that could explain existing disease or predict disease risk for individual patients or research participants. We have detailed how current databases contribute to this goal providing frequency data, literature reviews and predictions of causation for individual variants. For variant annotation, databases vary greatly in their ease of use, the use of standard mutation nomenclature, the comprehensiveness of the variant cataloging and the degree of expert opinion. Ultimately, we need a dynamic and comprehensive reference database of medically important variants that is easily cross referenced to exome and genome sequence data and allows for an accumulation of expert opinion. PMID:23962721

Johnston, Jennifer J; Biesecker, Leslie G

2013-08-19

116

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

2013-05-06

117

Genetic basis of hidden phenotypic variation revealed by increased translational readthrough in yeast.  

PubMed

Eukaryotic release factors 1 and 3, encoded by SUP45 and SUP35, respectively, in Saccharomyces cerevisiae, are required for translation termination. Recent studies have shown that, besides these two key factors, several genetic and epigenetic mechanisms modulate the efficiency of translation termination. These mechanisms, through modifying translation termination fidelity, were shown to affect various cellular processes, such as mRNA degradation, and in some cases could confer a beneficial phenotype to the cell. The most studied example of such a mechanism is [PSI+], the prion conformation of Sup35p, which can have pleiotropic effects on growth that vary among different yeast strains. However, genetic loci underlying such readthrough-dependent, background-specific phenotypes have yet to be identified. Here, we used sup35(C653R), a partial loss-of-function allele of the SUP35 previously shown to increase readthrough of stop codons and recapitulate some [PSI+]-dependent phenotypes, to study the genetic basis of phenotypes revealed by increased translational readthrough in two divergent yeast strains: BY4724 (a laboratory strain) and RM11_1a (a wine strain). We first identified growth conditions in which increased readthrough of stop codons by sup35(C653R) resulted in different growth responses between these two strains. We then used a recently developed linkage mapping technique, extreme QTL mapping (X-QTL), to identify readthrough-dependent loci for the observed growth differences. We further showed that variation in SKY1, an SR protein kinase, underlies a readthrough-dependent locus observed for growth on diamide and hydrogen peroxide. We found that the allelic state of SKY1 interacts with readthrough level and the genetic background to determine growth rate in these two conditions. PMID:22396662

Torabi, Noorossadat; Kruglyak, Leonid

2012-03-01

118

Genetic Basis of Hidden Phenotypic Variation Revealed by Increased Translational Readthrough in Yeast  

PubMed Central

Eukaryotic release factors 1 and 3, encoded by SUP45 and SUP35, respectively, in Saccharomyces cerevisiae, are required for translation termination. Recent studies have shown that, besides these two key factors, several genetic and epigenetic mechanisms modulate the efficiency of translation termination. These mechanisms, through modifying translation termination fidelity, were shown to affect various cellular processes, such as mRNA degradation, and in some cases could confer a beneficial phenotype to the cell. The most studied example of such a mechanism is [PSI+], the prion conformation of Sup35p, which can have pleiotropic effects on growth that vary among different yeast strains. However, genetic loci underlying such readthrough-dependent, background-specific phenotypes have yet to be identified. Here, we used sup35C653R, a partial loss-of-function allele of the SUP35 previously shown to increase readthrough of stop codons and recapitulate some [PSI+]-dependent phenotypes, to study the genetic basis of phenotypes revealed by increased translational readthrough in two divergent yeast strains: BY4724 (a laboratory strain) and RM11_1a (a wine strain). We first identified growth conditions in which increased readthrough of stop codons by sup35C653R resulted in different growth responses between these two strains. We then used a recently developed linkage mapping technique, extreme QTL mapping (X-QTL), to identify readthrough-dependent loci for the observed growth differences. We further showed that variation in SKY1, an SR protein kinase, underlies a readthrough-dependent locus observed for growth on diamide and hydrogen peroxide. We found that the allelic state of SKY1 interacts with readthrough level and the genetic background to determine growth rate in these two conditions.

Torabi, Noorossadat; Kruglyak, Leonid

2012-01-01

119

Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework.  

PubMed

Schizophrenia has long been thought to be clinically heterogeneous. A range of studies suggests that this is due to genetic heterogeneity. Some clinical features, such as negative symptoms, are associated with a greater risk of illness in relatives. Affected sibling pairs are correlated for clinical and course features as well as subforms of illness, and twin studies suggest that this is due to genetic factors. This is further supported by findings that subjects from families linked to some chromosomal regions may differ clinically from those from unlinked families. Moreover, some genes may affect clinical features without altering susceptibility (ie are modifier genes). High-risk genotypes may have quantitative, rather than categorical effects, and may influence milder or subclinical phenotypes. Another recent finding is that nonpsychotic relatives may have personality features that resemble those of their affected relatives. These findings taken together suggest that there may be several classes of gene action in schizophrenia: some genes may influence susceptibility only, others may influence clinical features only, and still others may have a mixed effect. Furthermore, subsets of these classes may affect personality and other traits in nonpsychotic relatives. Understanding these classes of gene action may help guide the design of linkage and association studies that have increased power. We describe five classes of genes and their predictions of the outcomes of family, twin, and several types of linkage studies. We go on to explore how these predictions can in turn be used to aid in the design of linkage studies. PMID:15618952

Fanous, A H; Kendler, K S

2005-01-01

120

Quantitative Phenotyping of Duchenne Muscular Dystrophy Dogs by Comprehensive Gait Analysis and Overnight Activity Monitoring  

PubMed Central

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.

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

2013-01-01

121

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

122

Quantitative Variations in the Bacterial Flora of Flatfish  

Microsoft Academic Search

SUMMARY: Bacterial counts made, over a period of 27 months, on skin, gut and gill samples of freshly caught skate and lemon sole, using sea water-based and tap water- based media in parallel, revealed a seasonal variation in the size of the bacterial populations on the fish throughout the year. Evidence is presented for the view that the occurrence of

J. Liston

1956-01-01

123

Identification of Metabolic Modifiers That Underlie Phenotypic Variations in Energy-Balance Regulation  

PubMed Central

OBJECTIVE Although recent studies have shown that human genomes contain hundreds of loci that exhibit signatures of positive selection, variants that are associated with adaptation in energy-balance regulation remain elusive. We reasoned that the difficulty in identifying such variants could be due to heterogeneity in selection pressure and that an integrative approach that incorporated experiment-based evidence and population genetics-based statistical judgments would be needed to reveal important metabolic modifiers in humans. RESEARCH DESIGN AND METHODS To identify common metabolic modifiers that underlie phenotypic variation in diabetes-associated or obesity-associated traits in humans, or both, we screened 207 candidate loci for regulatory single nucleotide polymorphisms (SNPs) that exhibited evidence of gene–environmental interactions. RESULTS Three SNPs (rs3895874, rs3848460, and rs937301) at the 5? gene region of human GIP were identified as prime metabolic-modifier candidates at the enteroinsular axis. Functional studies have shown that GIP promoter reporters carrying derived alleles of these three SNPs (haplotype GIP?1920A) have significantly lower transcriptional activities than those with ancestral alleles at corresponding positions (haplotype GIP?1920G). Consistently, studies of pregnant women who have undergone a screening test for gestational diabetes have shown that patients with a homozygous GIP?1920A/A genotype have significantly lower serum concentrations of glucose-dependent insulinotropic polypeptide (GIP) than those carrying an ancestral GIP?1920G haplotype. After controlling for a GIPR variation, we showed that serum glucose concentrations of patients carrying GIP?1920A/A homozygotes are significantly higher than that of those carrying an ancestral GIP?1920G haplotype (odds ratio 3.53). CONCLUSIONS Our proof-of-concept study indicates that common regulatory GIP variants impart a difference in GIP and glucose metabolism. The study also provides a rare example that identified the common variant-common phenotypic variation pattern based on evidence of moderate gene–environmental interactions.

Chang, Chia Lin; Cai, James J.; Cheng, Po Jen; Chueh, Ho Yen; Hsu, Sheau Yu Teddy

2011-01-01

124

Quantitative Trait Loci Responsible for Variation in Sexually Dimorphic Traits in Drosophila melanogaster  

Microsoft Academic Search

To understand the mechanisms of morphological evolution and species divergence, it is essential to elucidate the genetic basis of variation in natural populations. Sexually dimorphic characters, which evolve rapidly both within and among species, present attractive models for addressing these questions. In this report, we map quantitative trait loci (QTL) responsible for variation in sexually dimorphic traits (abdomi- nal pigmentation

Artyom Kopp; Rita M. Graze; Shizhong Xu; Sean B. Carroll; Sergey V. Nuzhdin

125

Quantitative Analysis of the Phenotypic Variability of Shoot Architecture in Two Grapevine (Vitis vinifera) Cultivars  

PubMed Central

Background and Aims Plant architecture and its interaction with agronomic practices and environmental constraints are determinants of the structure of the canopy, which is involved in carbon acquisition and fruit quality development. A framework for the quantitative analysis of grapevine (Vitis vinifera) shoot architecture, based on a set of topological and geometrical parameters, was developed for the identification of differences between cultivars and the origins of phenotypic variability. Methods Two commercial cultivars (‘Grenache N’, ‘Syrah’) with different shoot architectures were grown in pots, in well-irrigated conditions. Shoot topology was analysed, using a hidden semi-Markov chain and variable-order Markov chains to identify deviations from the normal pattern of succession of phytomer types (P0–P1–P2), together with kinematic analysis of shoot axis development. Shoot geometry was characterized by final internode and individual leaf area measurements. Key Results Shoot architecture differed significantly between cultivars. Secondary leaf area and axis length were greater for ‘Syrah’. Secondary leaf area distribution along the main axis also differed between cultivars, with secondary leaves preferentially located towards the basal part of the shoot in ‘Syrah’. The main factors leading to differences in leaf area between the cultivars were: (a) slight differences in main shoot structure, with the supplementary P0 phytomer on the lower part of the shoot in ‘Grenache N’, which bears a short branch; and (b) an higher rate and duration of development of branches bearing by P1–P2 phytomers related to P0 ones at the bottom of the shoot in ‘Syrah’. Differences in axis length were accounted for principally by differences in individual internode morphology, with ‘Syrah’ having significantly longer internodes. This trait, together with a smaller shoot diameter, may account for the characteristic ‘droopy’ habit of ‘Syrah’ shoots. Conclusions This study highlights the architectural parameters involved in the phenotypic variability of shoot architecture in two grapevine cultivars. Differences in primary shoot structure and in branch development potential accounted for the main differences in leaf area distribution between the two cultivars. By contrast, shoot shape seemed to be controlled by differences in axis length due principally to differences in internode length.

Louarn, Gaetan; Guedon, Yann; Lecoeur, Jeremie; Lebon, Eric

2007-01-01

126

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

127

Monitoring of Technical Variation in Quantitative High-Throughput Datasets  

PubMed Central

High-dimensional datasets can be confounded by variation from technical sources, such as batches. Undetected batch effects can have severe consequences for the validity of a study’s conclusion(s). We evaluate high-throughput RNAseq and miRNAseq as well as DNA methylation and gene expression microarray datasets, mainly from the Cancer Genome Atlas (TCGA) project, in respect to technical and biological annotations. We observe technical bias in these datasets and discuss corrective interventions. We then suggest a general procedure to control study design, detect technical bias using linear regression of principal components, correct for batch effects, and re-evaluate principal components. This procedure is implemented in the R package swamp, and as graphical user interface software. In conclusion, high-throughput platforms that generate continuous measurements are sensitive to various forms of technical bias. For such data, monitoring of technical variation is an important analysis step.

Lauss, Martin; Visne, Ilhami; Kriegner, Albert; Ringner, Markus; Jonsson, Goran; Hoglund, Mattias

2013-01-01

128

Patterns of quantitative genetic variation in multiple dimensions  

Microsoft Academic Search

A fundamental question for both evolutionary biologists and breeders is the extent to which genetic correlations limit the\\u000a ability of populations to respond to selection. Here I view this topic from three perspectives. First, I propose several nondimensional\\u000a statistics to quantify the genetic variation present in a suite of traits and to describe the extent to which correlations\\u000a limit their

Mark Kirkpatrick

2009-01-01

129

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

130

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

131

A mathematical model for a new mechanism of phenotypic variation in malaria.  

PubMed

The Py235 merozoite rhoptry protein of the rodent malaria agent Plasmodium (yoelii) yoeli is encoded by the Py235 multigene family whose members are transcribed during the parasite's asexual life-cycle in a fashion where single schizonts subsequently give rise to sets of merozoites containing distinct Py235 transcripts. Homologues of Py235 are found in other malaria species, and antibodies to both Py235 and P. falciparum homologues inhibit merozoite invasion, suggesting a unique survival strategy involving immune evasion and host adaptation. Using a mathematical approach to model this free-living stage of Plasmodium in interaction with specific antibodies and a heterogeneous red blood cell population, we investigate if, and under what conditions, this mechanism of clonal phenotypic variation can play a role in immune evasion and adaptation to a dynamic erythropoietic environment. PMID:16145932

Recker, M; Al-Bader, R; Gupta, S

2005-08-01

132

Phenotype variations in Lafora progressive myoclonus epilepsy: possible involvement of genetic modifiers?  

PubMed

Lafora progressive myoclonus epilepsy, also known as Lafora disease (LD), is the most severe and fatal form of progressive myoclonus epilepsy with its typical onset during the late childhood or early adolescence. LD is characterized by recurrent epileptic seizures and progressive decline in intellectual function. LD can be caused by defects in any of the two known genes and the clinical features of these two genetic groups are almost identical. The past one decade has witnessed considerable success in identifying the LD genes, their mutations, the cellular functions of gene products and on molecular basis of LD. Here, we briefly review the current literature on the phenotype variations, on possible presence of genetic modifiers, and candidate modifiers as targets for therapeutic interventions in LD. PMID:22456482

Singh, Shweta; Ganesh, Subramaniam

2012-03-29

133

The tRNA-Tyr gene family of Saccharomyces cerevisiae: agents of phenotypic variation and position effects on mutation frequency.  

PubMed Central

Extensive phenotypic diversity or variation exists in clonal populations of microorganisms and is thought to play a role in adaptation to novel environments. This phenotypic variation or instability, which occurs by multiple mechanisms, may be a form of cellular differentiation and a stochastic means for modulating gene expression. This work dissects a case of phenotypic variation in a clinically derived Saccharomyces cerevisiae strain involving a cox15 ochre mutation, which acts as a reporter. The ochre mutation reverts to sense at a low frequency while tRNA-Tyr ochre suppressors (SUP-o) arise at a very high frequency to produce this phenotypic variation. The SUP-o mutations are highly pleiotropic. In addition, although all SUP-o mutations within the eight-member tRNA-Tyr gene family suppress the ochre mutation reporter, there are considerable phenotypic differences among the different SUP-o mutants. Finally, and of particular interest, there is a strong position effect on mutation frequency within the eight-member tRNA-Tyr gene family, with one locus, SUP6, mutating at a much higher than average frequency and two other loci, SUP2 and SUP8, mutating at much lower than average frequencies. Mechanisms for the position effect on mutation frequency are evaluated.

Ito-Harashima, Sayoko; Hartzog, Phillip E; Sinha, Himanshu; McCusker, John H

2002-01-01

134

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

PubMed

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

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

2013-04-11

135

Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation.  

PubMed

Canalization, also known as developmental robustness, describes an organism's ability to produce the same phenotype despite genotypic variations and environmental influences. In Drosophila, Hsp90, the trithorax-group proteins and transposon silencing have been previously implicated in canalization. Despite this, the molecular mechanism underlying canalization remains elusive. Here using a Drosophila eye-outgrowth assay sensitized by the dominant Kr(irregular facets-1)(Kr(If-1)) allele, we show that the Piwi-interacting RNA (piRNA) pathway, but not the short interfering RNA or micro RNA pathway, is involved in canalization. Furthermore, we isolated a protein complex composed of Hsp90, Piwi and Hop, the Hsp70/Hsp90 organizing protein homolog, and we demonstrated the function of this complex in canalization. Our data indicate that Hsp90 and Hop regulate the piRNA pathway through Piwi to mediate canalization. Moreover, they point to epigenetic silencing of the expression of existing genetic variants and the suppression of transposon-induced new genetic variation as two major mechanisms underlying piRNA pathway-mediated canalization. PMID:21186352

Gangaraju, Vamsi K; Yin, Hang; Weiner, Molly M; Wang, Jianquan; Huang, Xiao A; Lin, Haifan

2010-12-26

136

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

137

Comparison of quantitative and molecular genetic variation of native vs. invasive populations of purple loosestrife (Lythrum salicaria L., Lythraceae).  

PubMed

Study of adaptive evolutionary changes in populations of invasive species can be advanced through the joint application of quantitative and population genetic methods. Using purple loosestrife as a model system, we investigated the relative roles of natural selection, genetic drift and gene flow in the invasive process by contrasting phenotypical and neutral genetic differentiation among native European and invasive North American populations (Q(ST) - F(ST) analysis). Our results indicate that invasive and native populations harbour comparable levels of amplified fragment length polymorphism variation, a pattern consistent with multiple independent introductions from a diverse European gene pool. However, it was observed that the genetic variation reduced during subsequent invasion, perhaps by founder effects and genetic drift. Comparison of genetically based quantitative trait differentiation (Q(ST)) with its expectation under neutrality (F(ST)) revealed no evidence of disruptive selection (Q(ST) > F(ST)) or stabilizing selection (Q(ST) < F(ST)). One exception was found for only one trait (the number of stems) showing significant sign of stabilizing selection across all populations. This suggests that there are difficulties in distinguishing the effects of nonadaptive population processes and natural selection. Multiple introductions of purple loosestrife may have created a genetic mixture from diverse source populations and increased population genetic diversity, but its link to the adaptive differentiation of invasive North American populations needs further research. PMID:19548895

Chun, Young Jin; Nason, John D; Moloney, Kirk A

2009-06-22

138

Semi-quantitative and structural metabolic phenotyping by direct infusion ion trap mass spectrometry and its application in genetical metabolomics  

PubMed Central

The identification of quantitative trait loci (QTL) for plant metabolites requires the quantitation of these metabolites across a large range of progeny. We developed a rapid metabolic profiling method using both untargeted and targeted direct infusion tandem mass spectrometry (DIMSMS) with a linear ion trap mass spectrometer yielding sufficient precision and accuracy for the quantification of a large number of metabolites in a high-throughput environment. The untargeted DIMSMS method uses top-down data-dependent fragmentation yielding MS2 and MS3 spectra. We have developed software tools to assess the structural homogeneity of the MS2 and MS3 spectra hence their utility for phenotyping and genetical metabolomics. In addition we used a targeted DIMS(MS) method for rapid quantitation of specific compounds. This method was compared with targeted LC/MS/MS methods for these compounds. The DIMSMS methods showed sufficient precision and accuracy for QTL discovery. We phenotyped 200 individual Lolium perenne genotypes from a mapping population harvested in two consecutive years. Computational and statistical analyses identified 246 nominal m/z bins with sufficient precision and homogeneity for QTL discovery. Comparison of the data for specific metabolites obtained by DIMSMS with the results from targeted LC/MS/MS analysis showed that quantitation by this metabolic profiling method is reasonably accurate. Of the top 100 MS1 bins, 22 ions gave one or more reproducible QTL across the 2 years. Copyright © 2009 John Wiley & Sons, Ltd.

Koulman, Albert; Cao, Mingshu; Faville, Marty; Lane, Geoff; Mace, Wade; Rasmussen, Susanne

2009-01-01

139

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

140

Genetic and phenotypic variation among geographically isolated populations of the globally threatened Dupont’s lark Chersophilus duponti  

Microsoft Academic Search

Identifying genetically and phenotypically distinct populations of threatened species is critical if we are to delineate appropriate plans for their conservation. We conducted an integrated analysis of population genetic structure, historical demographic events, current gene flow (all based on mtDNA sequences) and morphological variation of three geographically separated groups of populations of Dupont’s lark Chersophilus duponti, located in the Iberian

Jesús T. García; Francisco Suárez; Vicente Garza; María Calero-Riestra; Jorge Hernández; Javier Pérez-Tris

2008-01-01

141

Beetle visitations, and associations with quantitative variation of attractants in floral odors of Homalomena propinqua (Araceae)  

Microsoft Academic Search

This study investigated floral visitations of two beetles, Parastasia bimaculata (Scarabaeidae) and Chaloenus schawalleri (Chrysomelidae), and examined associations between beetle visitations and variation in attractant traits, such as quantitative\\u000a variations of attractants in floral odors and heat generation of spadices in Homalomena propinqua (Araceae). Observations showed P. bimaculata visited pistillate-phase inflorescences most frequently during heat generation, whereas C. schawalleri visited

Yuko Kumano-Nomura; Ryohei Yamaoka

2009-01-01

142

Genetic microheterogeneity and phenotypic variation of Helicobacter pylori arginase in clinical isolates  

PubMed Central

Background Clinical isolates of the gastric pathogen Helicobacter pylori display a high level of genetic macro- and microheterogeneity, featuring a panmictic, rather than clonal structure. The ability of H. pylori to survive the stomach acid is due, in part, to the arginase-urease enzyme system. Arginase (RocF) hydrolyzes L-arginine to L-ornithine and urea, and urease hydrolyzes urea to carbon dioxide and ammonium, which can neutralize acid. Results The degree of variation in arginase was explored at the DNA sequence, enzyme activity and protein expression levels. To this end, arginase activity was measured from 73 minimally-passaged clinical isolates and six laboratory-adapted strains of H. pylori. The rocF gene from 21 of the strains was cloned into genetically stable E. coli and the enzyme activities measured. Arginase activity was found to substantially vary (>100-fold) in both different H. pylori strains and in the E. coli model. Western blot analysis revealed a positive correlation between activity and amount of protein expressed in most H. pylori strains. Several H. pylori strains featured altered arginase activity upon in vitro passage. Pairwise alignments of the 21 rocF genes plus strain J99 revealed extensive microheterogeneity in the promoter region and 3' end of the rocF coding region. Amino acid S232, which was I232 in the arginase-negative clinical strain A2, was critical for arginase activity. Conclusion These studies demonstrated that H. pylori arginase exhibits extensive genotypic and phenotypic variation which may be used to understand mechanisms of microheterogeneity in H. pylori.

Hovey, Justin G; Watson, Emily L; Langford, Melanie L; Hildebrandt, Ellen; Bathala, Sangeetha; Bolland, Jeffrey R; Spadafora, Domenico; Mendz, George L; McGee, David J

2007-01-01

143

Genomic analysis of natural selection and phenotypic variation in high-altitude mongolians.  

PubMed

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

Xing, Jinchuan; Wuren, Tana; Simonson, Tatum S; Watkins, W Scott; Witherspoon, David J; Wu, Wilfred; Qin, Ga; Huff, Chad D; Jorde, Lynn B; Ge, Ri-Li

2013-07-18

144

Quantitative comparison of mapping methods between Human and Mammalian Phenotype Ontology  

PubMed Central

Researchers use animal studies to better understand human diseases. In recent years, large-scale phenotype studies such as Phenoscape and EuroPhenome have been initiated to identify genetic causes of a species' phenome. Species-specific phenotype ontologies are required to capture and report about all findings and to automatically infer results relevant to human diseases. The integration of the different phenotype ontologies into a coherent framework is necessary to achieve interoperability for cross-species research. Here, we investigate the quality and completeness of two different methods to align the Human Phenotype Ontology and the Mammalian Phenotype Ontology. The first method combines lexical matching with inference over the ontologies' taxonomic structures, while the second method uses a mapping algorithm based on the formal definitions of the ontologies. Neither method could map all concepts. Despite the formal definitions method provides mappings for more concepts than does the lexical matching method, it does not outperform the lexical matching in a biological use case. Our results suggest that combining both approaches will yield a better mappings in terms of completeness, specificity and application purposes.

2012-01-01

145

Quantitative Trait Loci Underlying Gene Product Variation: A Novel Perspective for Analyzing Regulation of Genome Expression  

Microsoft Academic Search

A methodology to dissect the genetic architecture of quantitative variation of numerous gene products simultaneously is proposed. For each individual of a segregating progeny, proteins extracted from a given organ are separated using two-dimensional electrophoresis, and their amounts are estimated with a computer-assisted system for spot quantification. Provided a complete genetic map is available, statistical procedures allow determination of the

C. Damerval; A. Maurice; J. M. Josse; D. de Vienne

1994-01-01

146

Quantitative Genetics of Ovariole Number in Drosophila melanogaster . II. Mutational Variation and Genotype-Environment Interaction  

Microsoft Academic Search

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 ( V M ) for these traits, estimated from mutation accumulation lines, were 4.75 and 1.97 3 10 2 4 times the en- vironmental variance ( V E ), respectively. The mutation

Marta L. Wayne; Trudy F. C. Mackay

147

Quantitative estimation of phenotypic plasticity: bridging the gap between the evolutionary concept and its ecological applications  

Microsoft Academic Search

Summary 1 Global change and emerging concepts in ecology and evolution are leading to a growing interest in phenotypic plasticity (PP), the environmentally contingent trait expression observed in a given genotype. The need to quantify PP in a simple manner in com- parative ecological studies has resulted in the prevalence of various indices instead of the classic approaches, i.e. a

FERNANDO VALLADARES; DAVID SANCHEZ-GOMEZ; MIGUEL A. ZAVALA

2006-01-01

148

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

2013-04-16

149

Speciation, phenotypic variation and plasticity: what can endocrine disruptors tell us?  

PubMed

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

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

2013-05-16

150

Mapping quantitative trait loci in F2 incorporating phenotypes of F3 progeny.  

PubMed Central

In plants and laboratory animals, QTL mapping is commonly performed using F(2) or BC individuals derived from the cross of two inbred lines. Typical QTL mapping statistics assume that each F(2) individual is genotyped for the markers and phenotyped for the trait. For plant traits with low heritability, it has been suggested to use the average phenotypic values of F(3) progeny derived from selfing F(2) plants in place of the F(2) phenotype itself. All F(3) progeny derived from the same F(2) plant belong to the same F(2:3) family, denoted by F(2:3). If the size of each F(2:3) family (the number of F(3) progeny) is sufficiently large, the average value of the family will represent the genotypic value of the F(2) plant, and thus the power of QTL mapping may be significantly increased. The strategy of using F(2) marker genotypes and F(3) average phenotypes for QTL mapping in plants is quite similar to the daughter design of QTL mapping in dairy cattle. We study the fundamental principle of the plant version of the daughter design and develop a new statistical method to map QTL under this F(2:3) strategy. We also propose to combine both the F(2) phenotypes and the F(2:3) average phenotypes to further increase the power of QTL mapping. The statistical method developed in this study differs from published ones in that the new method fully takes advantage of the mixture distribution for F(2:3) families of heterozygous F(2) plants. Incorporation of this new information has significantly increased the statistical power of QTL detection relative to the classical F(2) design, even if only a single F(3) progeny is collected from each F(2:3) family. The mixture model is developed on the basis of a single-QTL model and implemented via the EM algorithm. Substantial computer simulation was conducted to demonstrate the improved efficiency of the mixture model. Extension of the mixture model to multiple QTL analysis is developed using a Bayesian approach. The computer program performing the Bayesian analysis of the simulated data is available to users for real data analysis.

Zhang, Yuan-Ming; Xu, Shizhong

2004-01-01

151

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

PubMed Central

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

Stuart-Fox, Devi; Godinho, Raquel; Gouy de Bellocq, Joelle; Irwin, Nancy R.; Brito, Jose Carlos; Moussalli, Adnan; Siroky, Pavel; Hugall, Andrew F.; Baird, Stuart J. E.

2009-01-01

152

Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype  

Microsoft Academic Search

Copy number variation is common in the human genome with many regions, overlapping thousands of genes, now known to be deleted\\u000a or amplified. Aneuploidies and other forms of chromosomal imbalance have a wide range of adverse phenotypes and are a common\\u000a cause of birth defects resulting in significant morbidity and mortality. “Normal” copy number variants (CNVs) embedded within\\u000a the regions

Adam J. de SmithAnne; Anne L. Trewick; Alexandra I. F. Blakemore

2010-01-01

153

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

2012-05-03

154

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

155

Artificial neural networks for linkage analysis of quantitative gene expression phenotypes and evaluation of gene x gene interactions  

PubMed Central

Background Using single-nucleotide polymorphism (SNP) genotypes and selected gene expression phenotypes from 14 CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees provided for Genetic Analysis Workshop 15 (GAW15), we analyzed quantitative traits with artificial neural networks (ANNs). Our goals were to identify individual linkage signals and examine gene × gene interactions. First, we used classical multipoint methods to identify phenotypes having nominal linkage evidence at two or more loci. ANNs were then applied to sib-pair identity-by-descent (IBD) allele sharing across the genome as input variables and squared trait sums and differences for the sib pairs as output variables. The weights of the trained networks were analyzed to assess the linkage evidence at each locus as well as potential interactions between them. Results Loci identified by classical linkage analysis could also be identified by our ANN analysis. However some ANN results were noisy, and our attempts to use cross-validated training to avoid overtraining and thereby improve results were only partially successful. Potential interactions between loci with high-ranked weight measures were also evaluated, with the resulting patterns suggesting existence of both synergistic and antagonistic effects between loci. Conclusion Our results suggest that ANNs can serve as a useful method to analyze quantitative traits and are a potential tool for detecting gene × gene interactions. However, for the approach implemented here, optimizing the ANNs and obtaining stable results remains challenging.

Liu, Ying; Duan, Weimin; Paschall, Justin; Saccone, Nancy L

2007-01-01

156

Mapping quantitative-trait loci in humans by use of extreme concordant sib pairs: Selected sampling by parental phenotypes  

SciTech Connect

In two previous articles, we have considered sample sizes required to detect linkage for mapping quantitative-trait loci in humans, using extreme discordant sib pairs. Here, we examine further the use of extreme concordant sib pairs but consider the effect of parents` phenotypes. Sample sizes necessary to obtain a power of 80% with concordant sib pairs at a significance level of .0001 are given, stratified by parental phenotypes. When there is no residual correlation between sibs, the parental phenotypes have little impact on the sample sizes. When residual correlations between sibs exist, we show, however, that power can be considerably reduced by including extreme sib pairs when the parents also have similarly extreme values. Thus, we recommend the exclusion of such pairs from linkage studies. This recommendation reduces the required sample sizes by 3- to 28-fold. The degree of saving in the required sample sizes varies among different models and allele frequencies. The reduction is most dramatic (a 28-fold reduction) for a rare recessive gene. 5 refs., 6 tabs.

Zhang, Heping [Yale Univ. School of Medicine, New Haven, CT (United States); Risch, N. [Stanford Univ. School of Medicine, CA (United States)

1996-10-01

157

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

158

Phenotypic variation in plants produced from lateral buds, stem explants and single-cell-derived callus of potato  

Microsoft Academic Search

Summary  Plants regenerated directly from potato stem explants and from callus derived from single potato stem callus cells were compared\\u000a with plants from rooted lateral buds as controls. There was phenotypic variation in explant and cell cultures: grossly abnormal,\\u000a albino and green, shoot-like and root-like structures either failed to root or establish and survive in soil but most surviving\\u000a plants showed

A. C. Cassells; E. M. Goetz; S. Austin

1983-01-01

159

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

160

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

NSDL National Science Digital Library

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

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

2006-08-01

161

Quantitative trait loci analysis of phenotypic traits and principal components of maize tassel inflorescence architecture  

Microsoft Academic Search

Maize tassel inflorescence architecture is relevant to efficient production of F1 seed and yield performance of F1 hybrids. The objectives of this study were to identify genetic relationships among seven measured tassel inflorescence architecture traits and six calculated traits in a maize backcross population derived from two lines with differing tassel architectures, and identify Quantitative Trait Loci (QTL) involved in

N. Upadyayula; J. Wassom; M. O. Bohn; T. R. Rocheford

2006-01-01

162

Mapping quantitative trait loci controlling variation in forage quality traits in barley  

Microsoft Academic Search

Barley forage quality has a direct relationship to animal performance, but forage quality traits are often neglected or not\\u000a accessible to the plant breeders. Doubled haploid lines (145) from the cross Steptoe × Morex were grown in 2 years of trails\\u000a under irrigated conditions to evaluate the variation in forage quality characteristics, identify quantitative trait loci (QTL)\\u000a for these traits and determine if

Lisa Surber; Hussein Abdel-Haleem; Jack Martin; Pat Hensleigh; Dennis Cash; Jan Bowman; Tom Blake

2011-01-01

163

Quantitative trait loci on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18 control variation in levels of T and B lymphocyte subpopulations.  

PubMed

Lymphocyte subpopulation levels are used for prognosis and monitoring of a variety of human diseases, especially those with an infectious etiology. As a primary step to defining the major gene variation underlying these phenotypes, we conducted the first whole-genome screen for quantitative variation in lymphocyte count, CD4 T cell, CD8 T cell, B cell, and natural killer cell numbers, as well as CD4:CD8 ratio. The screen was performed in 15 of the CEPH families that form the main human genome genetic project mapping resource. Quantitative-trait loci (QTLs) that account for significant proportions of the phenotypic variance of lymphocyte subpopulations were detected on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18. The most significant QTL found was for CD4 levels on chromosome 8 (empirical P=.00005). Two regions of chromosome 4 showed significant linkage to CD4:CD8 ratio (empirical P=.00007 and P=.003). A QTL for the highly correlated measures of CD4 and CD19 levels colocalized at 18q21 (both P=.003). Similarly, a shared region of chromosome 1 was linked to CD8 and CD19 levels (P=.0001 and P=.002, respectively). Several of the identified chromosome regions are likely to harbor polymorphic candidate genes responsible for these important human phenotypes. Their discovery has important implications for understanding the generation of the immune repertoire and understanding immune-system homeostasis. More generally, these data show the power of an integrated human gene-mapping approach for heritable molecular phenotypes, using large pedigrees that have been extensively genotyped. PMID:11951176

Hall, M A; Norman, P J; Thiel, B; Tiwari, H; Peiffer, A; Vaughan, R W; Prescott, S; Leppert, M; Schork, N J; Lanchbury, J S

2002-04-09

164

Quantitative-Trait Loci on Chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18 Control Variation in Levels of T and B Lymphocyte Subpopulations  

PubMed Central

Lymphocyte subpopulation levels are used for prognosis and monitoring of a variety of human diseases, especially those with an infectious etiology. As a primary step to defining the major gene variation underlying these phenotypes, we conducted the first whole-genome screen for quantitative variation in lymphocyte count, CD4 T cell, CD8 T cell, B cell, and natural killer cell numbers, as well as CD4:CD8 ratio. The screen was performed in 15 of the CEPH families that form the main human genome genetic project mapping resource. Quantitative-trait loci (QTLs) that account for significant proportions of the phenotypic variance of lymphocyte subpopulations were detected on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18. The most significant QTL found was for CD4 levels on chromosome 8 (empirical P=.00005). Two regions of chromosome 4 showed significant linkage to CD4:CD8 ratio (empirical P=.00007 and P=.003). A QTL for the highly correlated measures of CD4 and CD19 levels colocalized at 18q21 (both P=.003). Similarly, a shared region of chromosome 1 was linked to CD8 and CD19 levels (P=.0001 and P=.002, respectively). Several of the identified chromosome regions are likely to harbor polymorphic candidate genes responsible for these important human phenotypes. Their discovery has important implications for understanding the generation of the immune repertoire and understanding immune-system homeostasis. More generally, these data show the power of an integrated human gene–mapping approach for heritable molecular phenotypes, using large pedigrees that have been extensively genotyped.

Hall, M. A.; Norman, P. J.; Thiel, B.; Tiwari, H.; Peiffer, A.; Vaughan, R. W.; Prescott, S.; Leppert, M.; Schork, N. J.; Lanchbury, J. S.

2002-01-01

165

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

166

A quantitative model of the relationship between phenotypic variance and heterozygosity at marker loci under partial selfing.  

PubMed Central

Negative relationships between allozyme heterozygosity and morphological variance have often been observed and interpreted as evidence for increased developmental stability in heterozygotes. However, inbreeding can also generate such relationships by decreasing heterozygosity at neutral loci and redistributing genetic variance at the same time. I here provide a quantitative genetic model of this process by analogy with heterozygosity-fitness relationships. Inbreeding generates negative heterozygosity-variance relationships irrespective of the genetic architecture of the trait. This holds for fitness traits as well as neutral traits, the effect being stronger for fitness traits under directional dominance or overdominance. The order of magnitude of heterozygosity-variance regressions is compatible with empirical data even with very low inbreeding. Although developmental stability effects cannot be excluded, inbreeding is a parsimonious explanation that should be seriously considered to explain correlations between heterozygosity and both mean and variance of phenotypes in natural populations.

David, P

1999-01-01

167

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

PubMed

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

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

2013-01-25

168

Testing the rare-alleles model of quantitative variation by artificial selection  

PubMed Central

The rare-alleles model of quantitative variation posits that a common allele (the `wild-type') and one or more rare alleles segregate at each locus affecting a quantitative trait; a scenario predicted by several distinct evolutionary hypotheses. Single locus arguments suggest that artificial selection should substantially increase the genetic variance (Vg) if the rare-alleles model is accurate. This paper tests the `?Vg prediction' using a large artificial selection experiment on flower size of Mimulus guttatus. Vg for flower size does evolve, increasing with selection for larger flower while decreasing in the other direction. These data are consistent with a model in which flower size variation is caused by rare, partially dominant alleles. However, this explanation becomes increasingly tenuous when considered with other data (correlated responses to selection and the effects of inbreeding). A combination of modern (marker-based mapping) and classical (biometric) techniques will likely to be required to determine the distribution of allele frequencies at loci influencing quantitative traits.

Kelly, John K.

2009-01-01

169

Estimation of Quantitative Trait Locus Effects with Epistasis by Variational Bayes Algorithms  

PubMed Central

Bayesian hierarchical shrinkage methods have been widely used for quantitative trait locus mapping. From the computational perspective, the application of the Markov chain Monte Carlo (MCMC) method is not optimal for high-dimensional problems such as the ones arising in epistatic analysis. Maximum a posteriori (MAP) estimation can be a faster alternative, but it usually produces only point estimates without providing any measures of uncertainty (i.e., interval estimates). The variational Bayes method, stemming from the mean field theory in theoretical physics, is regarded as a compromise between MAP and MCMC estimation, which can be efficiently computed and produces the uncertainty measures of the estimates. Furthermore, variational Bayes methods can be regarded as the extension of traditional expectation-maximization (EM) algorithms and can be applied to a broader class of Bayesian models. Thus, the use of variational Bayes algorithms based on three hierarchical shrinkage models including Bayesian adaptive shrinkage, Bayesian LASSO, and extended Bayesian LASSO is proposed here. These methods performed generally well and were found to be highly competitive with their MCMC counterparts in our example analyses. The use of posterior credible intervals and permutation tests are considered for decision making between quantitative trait loci (QTL) and non-QTL. The performance of the presented models is also compared with R/qtlbim and R/BhGLM packages, using a previously studied simulated public epistatic data set.

Li, Zitong; Sillanpaa, Mikko J.

2012-01-01

170

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

PubMed Central

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.

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

2012-01-01

171

Phenotypically Concordant and Discordant Monozygotic Twins Display Different DNA Copy-Number-Variation Profiles  

Microsoft Academic Search

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

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

2008-01-01

172

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

Microsoft Academic Search

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

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

2009-01-01

173

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

174

Functional genetic variation of human miRNAs and phenotypic consequences  

Microsoft Academic Search

A large number of human protein-coding genes are finely regulated by one or more microRNAs. Members of this small noncoding\\u000a RNA family have emerged as important post-transcriptional regulators of gene expression and are involved in a number of disease\\u000a phenotypes. Variability in the human genome is extensive and includes the common and rare single nucleotide polymorphisms\\u000a (SNPs) and copy number

Christelle Borel; Stylianos E. Antonarakis

2008-01-01

175

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

PubMed

Even though premating isolation is hypothesized to be a major driving force in speciation, its genetic basis is poorly known. In the noctuid moth Heliothis subflexa, one group of sex pheromone components, the acetates, emitted by the female, plays a crucial isolating role in preventing interspecific matings to males of the closely related Heliothis virescens, in which females do not produce acetates and males are repelled by them. We previously found intraspecific variation in acetates in H. subflexa: females in eastern North America contain significantly more acetates than females in Western Mexico. Here we describe the persistence of this intraspecific variation in laboratory-reared strains and the identification of one major quantitative trait locus (QTL), explaining 40% of the variance in acetate amounts. We homologized this intraspecific QTL to our previously identified interspecific QTL using restriction-associated DNA (RAD) tags. We found that a major intraspecific QTL overlaps with one of the two major interspecific QTL. To identify candidate genes underlying the acetate variation, we investigated a number of gene families with known or suspected acetyl- or acyltransferase activity. The most likely candidate genes did not map to our QTL, so that we currently hypothesize that a transcription factor underlies this QTL. Finding a single, large QTL that impacts variation in pheromone blends between and within species is, to our knowledge, the first such example for traits that have been demonstrated to affect premating isolation. PMID:23294019

Groot, A T; Staudacher, H; Barthel, A; Inglis, O; Schöfl, G; Santangelo, R G; Gebauer-Jung, S; Vogel, H; Emerson, J; Schal, C; Heckel, D G; Gould, F

2013-01-07

176

Lung structure phenotype variation in inbred mouse strains revealed through in vivo micro-CT imaging  

PubMed Central

Within pulmonary research, the development of mouse models has provided insight into disease development, progression, and treatment. Structural phenotypes of the lung in healthy inbred mouse strains are necessary for comparison to disease models. To date, progress in the assessment of lung function in these small animals using whole lung function tests has been made. However, assessment of in vivo lung structure of inbred mouse strains has yet to be well defined. Therefore, the link between the structure and function phenotypes is still unclear. With advancements in small animal imaging it is now possible to investigate lung structures such as the central and peripheral airways, whole lung, and lobar volumes of mice in vivo, through the use of micro-CT imaging. In this study, we performed in vivo micro-CT imaging of the C57BL/6, A/J, and BALB/c mouse strains using the intermittent iso-pressure breath hold (IIBH) technique. The resulting high-resolution images were used to extract lung structure phenotypes. The three-dimensional lobar structures and airways were defined and a meaningful mouse airway nomenclature was developed. In addition, using these techniques we have uncovered significant differences in the airway structures between inbred mouse strains in vivo.

Thiesse, Jacqueline; Namati, Eman; Sieren, Jessica C.; Smith, Amanda R.; Reinhardt, Joseph M.; Hoffman, Eric A.

2010-01-01

177

Deconstructing a complex molecular phenotype: population-level variation in individual venom proteins in Eastern Massasauga Rattlesnakes (Sistrurus c. catenatus).  

PubMed

Identifying the molecular basis for complex adaptations such as the toxic proteins used by venomous snakes to subdue and digest prey is an important step in understanding the evolutionary and functional basis for such traits. Recent proteomics-based analyses have made possible the identification of all constituent proteins in whole venom samples. Here we exploit this advance to study patterns of population-level variation in venom proteins from 254 adult eastern massasauga rattlesnakes (Sistrurus c. catenatus) collected from 10 populations. Analysis of presence-absence variation in specific proteins from 1D PAGE gels shows that: (1) The frequency spectra for individual protein bands is U-shaped with a large number of specific proteins either being consistently "common" or "rare" across populations possibly reflecting functional differences. (2) Multivariate axes which summarize whole venom variation consist of bands from all major types of proteins implying the integration of functionally distinct components within the overall venom phenotype. (3) There is significant differentiation in venom proteins across populations and the specific classes of proteins contributing to this differentiation have been identified. (4) Levels of population differentiation in venom proteins are not correlated with levels of neutral genetic differentiation, or genetically effective population sizes which argues that patterns of venom variation are not simply a consequence of population structure but leaves open the role of selection in generating population differences in venom. Our results identify particular classes of venom proteins and their associated genes as being fruitful targets for future studies of the molecular and functional basis for this complex adaptive phenotype. PMID:21394489

Lisle Gibbs, H; Chiucchi, James E

2011-03-11

178

Side-to-side earlobe variations with respect to surface area and shape: a quantitative study.  

PubMed

Side-to-side earlobe variations, based on the size of the earlobe surface area and a classification into earlobe types, were quantitatively analyzed in 58 female students, ranging from 20 to 22 years old. Using a new earlobe measurement technique, a closed-circuit outline of each ear was directly traced onto a clear polyethylene sheet, after which the surface area of the earlobe portion of each ear was identified, measured by a digital planimeter, and analyzed. Results revealed that side-to-side differences in the size of the earlobe surface area existed in all subjects. In contrast, based on classifying the earlobe shape into three types (i.e., tapering, square, or pendulous), differences in the mean earlobe surface area value among the three types were not significant. However, when the classification of the earlobe shape was reduced to only two types (pendulous or nonpendulous), the mean earlobe surface area value between the two types was highly significant. These results thus suggest that for a quantitative analysis of earlobe variations, classification of the earlobe shape into two types rather than into three types is the better method. This method makes it easy to distinguish earlobe differences. Further, if the earlobe differences are noted before ear piercing, a balanced ear piercing effect can be achieved. PMID:8638495

Nakamura, M; Ikeda, T; Shioya, N

179

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

PubMed

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. PMID:23321708

Tian-Bi, Y-N T; Jarne, P; Konan, J-N K; Utzinger, J; N'Goran, E K

2013-01-16

180

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

181

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

182

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

2011-03-29

183

Human C4 polymorphism: pedigree analysis of qualitative, quantitative, and functional parameters as a basis for phenotype interpretations.  

PubMed

Ten families with 82 members were investigated for C4A- and B polymorphism in a blind trial. Phenotyping was done on neuraminidase treated sera by immunofixation and simultaneously by hemolytic overlay electrophoresis. In addition Rg, Ch, BF, C2, HLA-A, B, C, DR, and GLO were determined. After decoding the samples the reliability of blind typing was found to be 84.4% according to segregation patterns. Inconsistencies occurred mostly when A4, A2, or A92 were present. The detection of silent A*Q0 and B*Q0 alleles was more critical than that of "difficult" allotypes. The quantitation of the C4A/B ratio by densitometry of stained gels or by conventional immunochemical measurements of serum C4 level could not substantially improve the identification of A*Q0 or B*Q0. C4 dependent activity in radial diffusion hemolysis showed satisfactory correspondence with the number of expressed C4B alleles. At least three haplotypes with two C4A genes (duplicated A genes) were observed as ascertained from offspring analysis in accordance with the MHC segregation pattern. Individuals with the duplicated C4A gene (C4A*3, A*2, in the absence of any other expressed A allele or together with C4A*92) showed only partial inhibition of Rodgers antisera. Partial inhibition of Chido antisera was seen in individuals with C4B 2 (in the absence of other B allotypes). The findings support the hypothesis of at least two structural C4 loci. They also demonstrate the inconsistency of quantitative data in the recognition of silent alleles. PMID:6420328

Mauff, G; Bender, K; Giles, C M; Goldmann, S; Opferkuch, W; Wachauf, B

1984-01-01

184

Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase.  

PubMed

We describe a family of seven boys affected by Lesch-Nyhan disease with various phenotypes. Further investigations revealed a mutation c.203T>C in the gene encoding HGprt of all members, with substitution of leucine to proline at residue 68 (p.Leu68Pro). Thus patients from this family display a wide variety of symptoms although sharing the same mutation. Mutant HGprt enzyme was prepared by site-directed mutagenesis and the kinetics of the enzyme revealed that the catalytic activity of the mutant was reduced, in association with marked reductions in the affinity towards phosphoribosylpyrophosphate (PRPP). Its Km for PRPP was increased 215-fold with hypoxanthine as substrate and 40-fold with guanine as substrate with associated reduced catalytic potential. Molecular modeling confirmed that the most prominent defect was the dramatically reduced affinity towards PRPP. Our studies suggest that the p.Leu68Pro mutation has a strong impact on PRPP binding and on stability of the active conformation. This suggests that factors other than HGprt activity per se may influence the phenotype of Lesch-Nyhan patients. PMID:24075303

Ceballos-Picot, Irène; Augé, Franck; Fu, Rong; Olivier-Bandini, Anne; Cahu, Julie; Chabrol, Brigitte; Aral, Bernard; de Martinville, Bérengère; Lecain, Jean-Paul; Jinnah, H A

2013-09-08

185

Phenotypic and genotypic variation among Capsicum annuum recombinant inbred lines resistant to bacterial spot.  

PubMed

A breeding program carried out under Brazilian growing conditions to obtain Capsicum annuum cultivars with disease resistance to bacterial spot (BS) produced 8 promising recombinant inbred lines (RILs). The present study aimed to characterize these RILs using phenotypic descriptors and molecular markers (inter-simple sequence repeat) and to confirm their resistance to BS. Twenty-two phenotypic descriptors and 15 inter-simple sequence repeat primers were used to characterize the RILs. The parent, UENF 1381, which is resistant to BS, and 'Casca Dura Ikeda', a traditional cultivar, were used as standards. Variability among genotypes was observed considering either binary or multicategorical characteristics, such as fruit length, fruit diameter, and fruit longitudinal and transversal section. Such variability in fruit traits can be exploited to develop new genotypes with BS resistance for various types of market consumption. RILs numbered 1, 3, and 6 were the most homogenous, whereas those coded 2, 5, 8, and 11 had the same level of heterogeneity as that observed in 'Casca Dura Ikeda'. Molecular analysis clustered the genotypes into 5 groups, with RILs 1, 2, 3, and 5 allocated in isolated groups. RILs 1, 2, 6, and 8 confirmed resistance to BS. Considering homogeneity level and BS resistance, RILs 1 and 6 were suitable for use as pre-cultivars in final tests to register and release two new C. annuum cultivars. PMID:23661448

Moreira, S O; Rodrigues, R; Oliveira, H S; Medeiros, A M; Sudré, C P; Gonçalves, L S A

2013-04-17

186

MitoLSDB: a comprehensive resource to study genotype to phenotype correlations in human mitochondrial DNA variations.  

PubMed

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

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

2013-04-09

187

Phenotypic variation in a core collection of common bean (Phaseolus vulgaris L.) in the Netherlands  

Microsoft Academic Search

Forty accessions, forming a core collection of mainly bush type of the common bean (Phaseolus vulgaris L.) germplasm in the Netherlands, were evaluated for 14 qualitative and quantitative traits at the Agricultural University,\\u000a Wageningen (WAU), the Netherlands in 1992. These and an additional 117 Dutch accessions, mainly collected in private home\\u000a gardens, were also evaluated for phaseolin seed protein pattern,

A. C. Zeven; J. Waninge; Th. van Hintum; S. P. Singh

1999-01-01

188

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

189

Strategy for minimizing between-study variation of large-scale phenotypic experiments using multivariate analysis.  

PubMed

We have developed a multistep strategy that integrates data from several large-scale experiments that suffer from systematic between-experiment variation. This strategy removes such variation that would otherwise mask differences of interest. It was applied to the evaluation of wood chemical analysis of 736 hybrid aspen trees: wild-type controls and transgenic trees potentially involved in wood formation. The trees were grown in four different greenhouse experiments imposing significant variation between experiments. Pyrolysis coupled to gas chromatography/mass spectrometry (Py-GC/MS) was used as a high throughput-screening platform for fingerprinting of wood chemotype. Our proposed strategy includes quality control, outlier detection, gene specific classification, and consensus analysis. The orthogonal projections to latent structures discriminant analysis (OPLS-DA) method was used to generate the consensus chemotype profiles for each transgenic line. These were thereafter compiled to generate a global dataset. Multivariate analysis and cluster analysis techniques revealed a drastic reduction in between-experiment variation that enabled a global analysis of all transgenic lines from the four independent experiments. Information from in-depth analysis of specific transgenic lines and independent peak identification validated our proposed strategy. PMID:22978754

Pinto, Rui C; Gerber, Lorenz; Eliasson, Mattias; Sundberg, Björn; Trygg, Johan

2012-10-01

190

Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)  

PubMed Central

Background Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10–12) and small (3–4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China. Methodology/Principal Findings Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters. Conclusions/Significance These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

Zhang, Xue-Ying; Zhang, Qiang; Wang, De-Hua

2011-01-01

191

Rapid visualisation of microarray copy number data for the detection of structural variations linked to a disease phenotype.  

PubMed

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. PMID:22912880

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

2012-08-17

192

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

193

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

Microsoft Academic Search

Sex-specific variation in morphology (sexual dimorphism) is a prevalent phenomenon among animals, and both dietary intake\\u000a and resource allocation strategies influence sexually dimorphic traits (e.g., body size or composition). However, we investigated\\u000a whether assimilation efficiency (AE), an intermediate step between dietary intake and allocation, can also vary between the\\u000a sexes. Specifically, we tested whether sex-based differences in AE can explain

Zachary R. StahlschmidtJon; Jon R. Davis; Dale F. DeNardo

2011-01-01

194

Domestication of Irvingia gabonensis : 1. Phenotypic variation in fruits and kernels in two populations from Cameroon  

Microsoft Academic Search

Twenty four fruits from each of 52 Irvingia gabonensis trees from two villages (Nko'ovos II and Elig Nkouma) of the humid lowland forest zone of Cameroon (West Africa) were assessed to determine the extent of variation in ten fruit, nut (endocarp), and kernel (cotyledon) characteristics. Highly significant differences were found in fruit length (Range = 46.2 to 77.3 mm), fruit

A. R. Atangana; Z. Tchoundjeu; J. M. Fondoun; E. Asaah; M. Ndoumbe; R. R. B. Leakey

2001-01-01

195

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

196

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

197

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

198

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

2010-04-15

199

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

200

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

PubMed Central

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

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

2012-01-01

201

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

PubMed

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

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

2012-01-27

202

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

203

COL1A1 Sp1 variation and bone phenotypes in an Italian population  

PubMed Central

Summary Background Osteoporosis is the most common metabolic bone disorder of the elderly, affecting the normal bone turnover with an increased bone resorption and subsequent higher risk of fragility fractures. Collagen type 1 is the most represented protein in bone matrix. A genetic variation (Sp1) in intron 1 of COL1A1 gene has been associated to modulation of expression of the alpha 1 chain of collagen type 1 and it is considered a candidate polymorphism for predisposition to osteoporosis status and fragility fractures. Association studies, in ethnically different populations, are needed to strongly confirm the role of this polymorphism in bone metabolism. Materials and methods We enrolled over 2,000 Italian individuals and studied their bone mineral density (BMD) and fractures in relation to age, sex and body mass index (BMI). Moreover, we analyzed the distribution of Sp1 polymorphism in these individuals and associated it to normal bone status, osteopenic condition or osteoporosis diagnosis, BMD and the presence of low-trauma fractures. Results The most rare ss genotype showed a trend for osteoporosis diagnosis with respect to both normal and osteopenic status. The same genotype resulted to be associated to lower values of BMD both at spine and femur sites. No association was found with fractures. Discussion In conclusion the presence of the homozygote ss genotype seemed to predispose to osteoporosis diagnosis and to be more frequent in subjects with lower spine and femur BMD values.

Marini, Francesca; Parri, Simone; Masi, Laura; Ciuffi, Simone; Guazzini, Andrea; Fabbri, Sergio; Luzi, Ettore; Cianferotti, Luisella; Brandi, Maria Luisa

2013-01-01

204

Alcohol-responsive myoclonic dystonia in a large family: dominant inheritance and phenotypic variation.  

PubMed

Alcohol-responsive myoclonic dystonia is reported in 26 individuals in a six-generation family, thus indicating autosomal dominant inheritance. Twenty affected family members aged between 3 and 56 years were examined on one occasion. Myoclonus in arms, shoulder, and neck distribution was seen in 17, with occasional generalized jerks in 14. Leg dystonia/hemidystonia was seen in two infant cases, writer's cramp in seven, torticollis/retrocollis in two, and finger tremor in three. The onset of myoclonus was regularly reported from 2 to 3 years of age, the onset of leg dystonia/hemidystonia from 6 to 18 months of age, writer's cramp from early school age, and neck dystonia from late teenage. The effect of alcohol had been noted in 10 individuals, and seven of them abused alcohol. Once established, the neurological signs did not progress significantly. Leg dystonia resolved in two juvenile members. Two adult members had recovered from myoclonus: one elderly man and one posthemorrhagic spastic hemiplegic man. Extensive family investigation is necessary to clarify the clinical variation of this autosomal dominant disorder of involuntary movements. PMID:2259350

Kyllerman, M; Forsgren, L; Sanner, G; Holmgren, G; Wahlström, J; Drugge, U

1990-01-01

205

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

206

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

2011-07-28

207

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

208

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

209

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

2012-02-28

210

Evidence for the genetic control of estradiol-regulated responses. Implications for variation in normal and pathological hormone-dependent phenotypes.  

PubMed Central

The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.

Griffith, J. S.; Jensen, S. M.; Lunceford, J. K.; Kahn, M. W.; Zheng, Y.; Falase, E. A.; Lyttle, C. R.; Teuscher, C.

1997-01-01

211

Evidence for the genetic control of estradiol-regulated responses. Implications for variation in normal and pathological hormone-dependent phenotypes.  

PubMed

The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component. PMID:9176411

Griffith, J S; Jensen, S M; Lunceford, J K; Kahn, M W; Zheng, Y; Falase, E A; Lyttle, C R; Teuscher, C

1997-06-01

212

Quantitative Assessment of the Importance of Phenotypic Plasticity in Adaptation to Climate Change in Wild Bird Populations  

PubMed Central

Predictions about the fate of species or populations under climate change scenarios typically neglect adaptive evolution and phenotypic plasticity, the two major mechanisms by which organisms can adapt to changing local conditions. As a consequence, we have little understanding of the scope for organisms to track changing environments by in situ adaptation. Here, we use a detailed individual-specific long-term population study of great tits (Parus major) breeding in Wytham Woods, Oxford, UK to parameterise a mechanistic model and thus directly estimate the rate of environmental change to which in situ adaptation is possible. Using the effect of changes in early spring temperature on temporal synchrony between birds and a critical food resource, we focus in particular on the contribution of phenotypic plasticity to population persistence. Despite using conservative estimates for evolutionary and reproductive potential, our results suggest little risk of population extinction under projected local temperature change; however, this conclusion relies heavily on the extent to which phenotypic plasticity tracks the changing environment. Extrapolating the model to a broad range of life histories in birds suggests that the importance of phenotypic plasticity for adjustment to projected rates of temperature change increases with slower life histories, owing to lower evolutionary potential. Understanding the determinants and constraints on phenotypic plasticity in natural populations is thus crucial for characterising the risks that rapidly changing environments pose for the persistence of such populations.

Vedder, Oscar; Bouwhuis, Sandra; Sheldon, Ben C.

2013-01-01

213

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

2012-11-01

214

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

215

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

PubMed Central

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

Haase, Christiane L.; Frikke-Schmidt, Ruth; Nordestgaard, B?rge G.; Tybjaerg-Hansen, Anne

2012-01-01

216

Quantitative measurement of cell-free plasma DNA and applications for detecting tumor genetic variation and promoter methylation in a clinical setting.  

PubMed

An elevated cell-free DNA (cfDNA) level is often reported in patients with advanced cancer and is thought to represent nuclear material from a distant inaccessible tumor. cfDNA can become a valuable source to monitor tumor dynamics and evaluate genetic markers for predictive, prognostic, and diagnostic testing. DNA extraction and quantification were optimized with plasma collected from 20 patients with advanced cancer and 16 healthy controls. Plasma cfDNA from patients with advanced cancer was evaluated for TP53 genetic variation and methylation status of CpG islands in several promoters of known disease-related genes. Tumor biopsy and corresponding plasma specimens were collected from study participants to determine whether the same genetic variations were present in both samples. The cfDNA isolation method provided a lower DNA detection limit of 144 pg, equivalent to DNA from approximately 24 cells. Normal pooled human plasma cfDNA averaged 110 copies/mL of the ACTB gene. Extracted cfDNA was suitable for gene-specific variant detection, sequencing, and promoter methylation analysis. DNA extracted from tumor biopsy and corresponding plasma specimens from two patients with advanced cancer revealed an identical, nonsynonymous variant present in both samples. Immunohistochemical analysis confirmed the TP53 mutant phenotype in the tumor specimens. Quantitative measurement of cfDNA represents a useful biomarker to follow treatment outcome and is a valuable tool with which to characterize specific genetic alterations for both patient selection and personalized treatment. PMID:22579630

Kadam, Sunil K; Farmen, Mark; Brandt, John T

2012-05-08

217

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates.  

PubMed

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals. PMID:16152574

Bacanu, Silviu-Alin; Bulik, Cynthia M; Klump, Kelly L; Fichter, Manfred M; Halmi, Katherine A; Keel, Pamela; Kaplan, Allan S; Mitchell, James E; Rotondo, Alessandro; Strober, Michael; Treasure, Janet; Woodside, D Blake; Sonpar, Vibhor A; Xie, Weiting; Bergen, Andrew W; Berrettini, Wade H; Kaye, Walter H; Devlin, Bernie

2005-11-01

218

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates  

PubMed Central

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR) and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum Body Mass Index (BMI), concern over mistakes (CM) and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals.

Bacanu, Silviu-Alin; Bulik, Cynthia M.; Klump, Kelly L.; Fichter, Manfred M.; Halmi, Katherine A.; Keel, Pamela; Kaplan, Alan S.; Mitchell, James E.; Rotondo, Alessandro; Strober, Michael; Treasure, Janet; Woodside, D. Blake; Sonpar, Vibhor A.; Xie, Weiting; Bergen, Andrew W.; Berrettini, Wade H.; Kaye, Walter H.; Devlin, Bernie

2008-01-01

219

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

220

Genetically determined variation in the number of phenotypically defined hematopoietic progenitor and stem cells and in their response to early-acting cytokines  

Microsoft Academic Search

Quantitative trait analysis may shed light on mechanisms regulating hematopoi- esis in vivo. Strain-dependent variation existed among C57BL\\/6 (B6), DBA\\/2, and BXD recombinant inbred mice in the re- sponsiveness of primitive progenitor cells to the early-acting cytokines kit ligand, flt3 ligand, and thrombopoietin. A signifi- cant quantitative trait locus was found on chromosome 2 that could not be con- firmed

Els Henckaerts; Hartmut Geiger; Jessica C. Langer; Patricia Rebollo; Gary Van Zant; Hans-Willem Snoeck

2002-01-01

221

Body mass index as a phenotypic expression of adiposity: quantitative contribution of muscularity in a population-based sample  

Microsoft Academic Search

Objective:Although widely applied as a phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI) is also acknowledged to reflect muscularity even though relevant studies directly measuring skeletal muscle (SM) mass are lacking. The current study aimed to fill this important gap by applying advanced imaging methods to test the hypothesis that, after controlling first for adiposity,

S B Heymsfield; R Scherzer; A Pietrobelli; C E Lewis; C Grunfeld

2009-01-01

222

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

223

Genetic strain differences in learned fear inhibition associated with variation in neuroendocrine, autonomic, and amygdala dendritic phenotypes.  

PubMed

Mood and anxiety disorders develop in some but not all individuals following exposure to stress and psychological trauma. However, the factors underlying individual differences in risk and resilience for these disorders, including genetic variation, remain to be determined. Isogenic inbred mouse strains provide a valuable approach to elucidating these factors. Here, we performed a comprehensive examination of the extinction-impaired 129S1/SvImJ (S1) inbred mouse strain for multiple behavioral, autonomic, neuroendocrine, and corticolimbic neuronal morphology phenotypes. We found that S1 exhibited fear overgeneralization to ambiguous contexts and cues, impaired context extinction and impaired safety learning, relative to the (good-extinguishing) C57BL/6J (B6) strain. Fear overgeneralization and impaired extinction was rescued by treatment with the front-line anxiety medication fluoxetine. Telemetric measurement of electrocardiogram signals demonstrated autonomic disturbances in S1 including poor recovery of fear-induced suppression of heart rate variability. S1 with a history of chronic restraint stress displayed an attenuated corticosterone (CORT) response to a novel, swim stressor. Conversely, previously stress-naive S1 showed exaggerated CORT responses to acute restraint stress or extinction training, insensitivity to dexamethasone challenge, and reduced hippocampal CA3 glucocorticoid receptor mRNA, suggesting downregulation of negative feedback control of the hypothalamic-pituitary-adrenal axis. Analysis of neuronal morphology in key neural nodes within the fear and extinction circuit revealed enlarged dendritic arbors in basolateral amygdala neurons in S1, but normal infralimbic cortex and prelimbic cortex dendritic arborization. Collectively, these data provide convergent support for the utility of the S1 strain as a tractable model for elucidating the neural, molecular and genetic basis of persistent, excessive fear. PMID:22334122

Camp, Marguerite C; Macpherson, Kathryn P; Lederle, Lauren; Graybeal, Carolyn; Gaburro, Stefano; Debrouse, Lauren M; Ihne, Jessica L; Bravo, Javier A; O'Connor, Richard M; Ciocchi, Stephane; Wellman, Cara L; Lüthi, Andreas; Cryan, John F; Singewald, Nicolas; Holmes, Andrew

2012-02-15

224

Genetic Strain Differences in Learned Fear Inhibition Associated with Variation in Neuroendocrine, Autonomic, and Amygdala Dendritic Phenotypes  

PubMed Central

Mood and anxiety disorders develop in some but not all individuals following exposure to stress and psychological trauma. However, the factors underlying individual differences in risk and resilience for these disorders, including genetic variation, remain to be determined. Isogenic inbred mouse strains provide a valuable approach to elucidating these factors. Here, we performed a comprehensive examination of the extinction-impaired 129S1/SvImJ (S1) inbred mouse strain for multiple behavioral, autonomic, neuroendocrine, and corticolimbic neuronal morphology phenotypes. We found that S1 exhibited fear overgeneralization to ambiguous contexts and cues, impaired context extinction and impaired safety learning, relative to the (good-extinguishing) C57BL/6J (B6) strain. Fear overgeneralization and impaired extinction was rescued by treatment with the front-line anxiety medication fluoxetine. Telemetric measurement of electrocardiogram signals demonstrated autonomic disturbances in S1 including poor recovery of fear-induced suppression of heart rate variability. S1 with a history of chronic restraint stress displayed an attenuated corticosterone (CORT) response to a novel, swim stressor. Conversely, previously stress-naive S1 showed exaggerated CORT responses to acute restraint stress or extinction training, insensitivity to dexamethasone challenge, and reduced hippocampal CA3 glucocorticoid receptor mRNA, suggesting downregulation of negative feedback control of the hypothalamic–pituitary–adrenal axis. Analysis of neuronal morphology in key neural nodes within the fear and extinction circuit revealed enlarged dendritic arbors in basolateral amygdala neurons in S1, but normal infralimbic cortex and prelimbic cortex dendritic arborization. Collectively, these data provide convergent support for the utility of the S1 strain as a tractable model for elucidating the neural, molecular and genetic basis of persistent, excessive fear.

Camp, Marguerite C; MacPherson, Kathryn P; Lederle, Lauren; Graybeal, Carolyn; Gaburro, Stefano; DeBrouse, Lauren M; Ihne, Jessica L; Bravo, Javier A; O'Connor, Richard M; Ciocchi, Stephane; Wellman, Cara L; Luthi, Andreas; Cryan, John F; Singewald, Nicolas; Holmes, Andrew

2012-01-01

225

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

226

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

Microsoft Academic Search

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

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

2007-01-01

227

High Genetic and Epigenetic Stability in Coffea arabica Plants Derived from Embryogenic Suspensions and Secondary Embryogenesis as Revealed by AFLP, MSAP and the Phenotypic Variation Rate  

PubMed Central

Embryogenic suspensions that involve extensive cell division are risky in respect to genome and epigenome instability. Elevated frequencies of somaclonal variation in embryogenic suspension-derived plants were reported in many species, including coffee. This problem could be overcome by using culture conditions that allow moderate cell proliferation. In view of true-to-type large-scale propagation of C. arabica hybrids, suspension protocols based on low 2,4-D concentrations and short proliferation periods were developed. As mechanisms leading to somaclonal variation are often complex, the phenotypic, genetic and epigenetic changes were jointly assessed so as to accurately evaluate the conformity of suspension-derived plants. The effects of embryogenic suspensions and secondary embryogenesis, used as proliferation systems, on the genetic conformity of somatic embryogenesis-derived plants (emblings) were assessed in two hybrids. When applied over a 6 month period, both systems ensured very low somaclonal variation rates, as observed through massive phenotypic observations in field plots (0.74% from 200 000 plant). Molecular AFLP and MSAP analyses performed on 145 three year-old emblings showed that polymorphism between mother plants and emblings was extremely low, i.e. ranges of 0–0.003% and 0.07–0.18% respectively, with no significant difference between the proliferation systems for the two hybrids. No embling was found to cumulate more than three methylation polymorphisms. No relation was established between the variant phenotype (27 variants studied) and a particular MSAP pattern. Chromosome counting showed that 7 of the 11 variant emblings analyzed were characterized by the loss of 1–3 chromosomes. This work showed that both embryogenic suspensions and secondary embryogenesis are reliable for true-to-type propagation of elite material. Molecular analyses revealed that genetic and epigenetic alterations are particularly limited during coffee somatic embryogenesis. The main change in most of the rare phenotypic variants was aneuploidy, indicating that mitotic aberrations play a major role in somaclonal variation in coffee.

Bobadilla Landey, Roberto; Cenci, Alberto; Georget, Frederic; Bertrand, Benoit; Camayo, Gloria; Dechamp, Eveline; Herrera, Juan Carlos; Santoni, Sylvain; Lashermes, Philippe; Simpson, June; Etienne, Herve

2013-01-01

228

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

Microsoft Academic Search

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

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

2008-01-01

229

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

230

Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.  

PubMed

Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease-related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results. We performed ordered subset analysis (OSA) and quantitative trait linkage (QTL) using serum lipoproteins and microsatellite markers in 346 families with early-onset CAD. OSA defined homogeneous subsets and calculated lod scores across a chromosome after ranking families by mean lipoprotein values. QTL used variance components analysis. We found significantly increased linkage to chromosome 3q13 (LOD 5.10, p = 0.008) in families with higher HDL cholesterol, lower LDL and total cholesterol, lower triglycerides, and fewer CAD risk factors, possibly due to a concentrated non-lipoprotein-related genetic effect. OSA identified linkage on chromosome 5q34 in families with higher cholesterol, possibly representing a hereditary lipoprotein phenotype. Multiple QTLs were identified, with the strongest for: total cholesterol on chromosome 5q14 (LOD 4.3); LDL on 20p12 (LOD 3.97); HDL on 3p14 (LOD 1.65); triglycerides on 18q22 (LOD 1.43); and HDL/TC ratio on 3q27-28 (LOD 2.06). Our findings suggest the presence of etiologic heterogeneity in families with early-onset CAD, potentially due to differential effects of lipoprotein phenotypes. Candidate genes are under investigation. PMID:17044848

Shah, S H; Kraus, W E; Crossman, D C; Granger, C B; Haines, J L; Jones, C J H; Mooser, V; Huang, L; Haynes, C; Dowdy, E; Vega, G L; Grundy, S M; Vance, J M; Hauser, E R

2006-11-01

231

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

232

Whole genome survey of copy number variation in the spontaneously hypertensive rat: relationship to quantitative trait loci, gene expression, and blood pressure.  

PubMed

Copy number variation has emerged recently as an important genetic mechanism leading to phenotypic heterogeneity. The aim of our study was to determine whether copy number variants (CNVs) exist between the spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat, whether these map to quantitative trait loci in the rat and whether CNVs associate with gene expression or blood pressure differences between the 2 strains. We performed a comparative genomic hybridization assay between SHR and Wistar-Kyoto strains using a whole-genome array. In total, 16 CNVs were identified and validated (6 because of a relative loss of copy number in the SHR and 10 because of a relative gain). CNVs were present on rat autosomes 1, 3, 4, 6, 7, 10, 14, and 17 and varied in size from 10.0 kb to 1.6 Mb. Most of these CNVs mapped to chromosomal regions within previously identified quantitative trait loci, including those for blood pressure in the SHR. Transcriptomic experiments confirmed differences in the renal expression of several genes (including Ms4a6a, Ndrg3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between SHR and Wistar-Kyoto rats. In F(2) animals derived from an SHRxWistar-Kyoto cross, we also found a significant increase in blood pressure associated with an increase in copy number in the Egln1 gene. Our findings suggest that CNVs may play a role in the susceptibility to hypertension and related traits in the SHR. PMID:20231529

Charchar, Fadi J; Kaiser, Michael; Bingham, Andrew J; Fotinatos, Nina; Ahmady, Fahima; Tomaszewski, Maciej; Samani, Nilesh J

2010-03-15

233

Variation in Seed Dormancy Quantitative Trait Loci in Arabidopsis thaliana Originating from One Site  

Microsoft Academic Search

A Quantitative Trait Locus (QTL) analysis was performed using two novel Recombinant Inbred Line (RIL) populations, derived from the progeny between two Arabidopsis thaliana genotypes collected at the same site in Kyoto (Japan) crossed with the reference laboratory strain Landsberg erecta (Ler). We used these two RIL populations to determine the genetic basis of seed dormancy and flowering time, which

Rebecca A. Silady; Sigi Effgen; Maarten Koornneef; Matthieu Reymond; Daniel J. Kliebenstein

2011-01-01

234

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

235

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

236

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

237

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

238

Phenotypic and genetic variations and correlations in multitrait developmental instability: a multivariate Bayesian model applied to Speckled Wood butterfly (Pararge aegeria) wing measurements.  

PubMed

Phenotypic and genetic variation and covariation in developmental instability (DI) have been the subject of many debates. In this paper we develop and apply a statistical model in a Bayesian context to analyse different traits simultaneously in a multivariate model of DI. We apply the model to measurements of yellow spots on the front wing of the Speckled Wood butterfly (Pararge aegeria L.) in a full-sib breeding experiment. We estimated the posterior distribution of the broad-sense heritability of DI averaged across the five yellow spots, which had a median of 0.19 and a 95% credibility interval ranging between 0.04 and 0.64. Phenotypic and genetic correlations in DI could not be estimated accurately with the present sample size. Yellow spots 4 and 5 appeared to show some degree of developmental integration. The importance of this model and its possible extensions are discussed. PMID:17894909

Van Dongen, Stefan; Talloen, Willem

2007-06-01

239

Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras  

SciTech Connect

Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2/sup +/) thymocytes, which reaches maximum number of 10 to 20 x 10/sup 6/ cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1/sup +/) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 10/sup 6/). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype.

Ceredig, R.; McDonald, H.R.

1982-02-01

240

Consequences of recombination rate variation on quantitative trait locus mapping studies. Simulations based on the Drosophila melanogaster genome.  

PubMed Central

We examine the effect of variation in gene density per centimorgan on quantitative trait locus (QTL) mapping studies using data from the Drosophila melanogaster genome project and documented regional rates of recombination. There is tremendous variation in gene density per centimorgan across this genome, and we observe that this variation can cause systematic biases in QTL mapping studies. Specifically, in our simulated mapping experiments of 50 equal-effect QTL distributed randomly across the physical genome, very strong QTL are consistently detected near the centromeres of the two major autosomes, and few or no QTL are often detected on the X chromosome. This pattern persisted with varying heritability, marker density, QTL effect sizes, and transgressive segregation. Our results are consistent with empirical data collected from QTL mapping studies of this species and its close relatives, and they explain the "small X-effect" that has been documented in genetic studies of sexual isolation in the D. melanogaster group. Because of the biases resulting from recombination rate variation, results of QTL mapping studies should be taken as hypotheses to be tested by additional genetic methods, particularly in species for which detailed genetic and physical genome maps are not available.

Noor, M A; Cunningham, A L; Larkin, J C

2001-01-01

241

Quantitative patterns of morphological variation in the appendicular skeleton of the Early Cretaceous bird Confuciusornis  

Microsoft Academic Search

Confuciusornis sanctus stands out among the remarkable diversity of birds of the Jehol biota (Lower Cretaceous, Liaoning Province, China). Its basal position in the phylogenetic tree of birds, combined with the exceptional number of well-preserved, largely complete and articulated specimens, makes it a perfect model system for studying the variation, development and life history of early Mesozoic birds. A comprehensive

Jesús Marugán-Lobón; Luis M. Chiappe; Shuan Ji; Zhonghe Zhou; Gao Chunling; Dongyu Hu; Qinjing Meng

2011-01-01

242

Quantitative analysis of variation of organic carbon mass and content in source rock during evolution process  

Microsoft Academic Search

According to the mass conservation principle of organic carbon, a mathematical model of organic carbon mass compensation coefficient is established to indicate the variation of organic carbon mass. Considering the influence of organic carbon hydrocarbon generation, hydrocarbon expulsion and rock weight loss, a mathematical model for calculating changes in organic carbon content is also established. Forward method is used to

Zhou Zongying

2009-01-01

243

Individual variation in growth trajectories: phenotypic and genetic correlations in ontogeny of the house finch (Carpodacus mexicanus)  

Microsoft Academic Search

We studied patterns of growth in a recently established natural population of the house finch (Carpodacus mexicanus) to examine whether phenotypic and genetic covariation among age-specific trait values is likely to constrain morphological change favoured by selection acting on adults. We found variable patterns of allometric relationships during ontogeny, and documented relatively weak covariations among ages or among traits in

Badyaev; T. E. MARTIN

2000-01-01

244

GENETIC VARIATION AT THE PERILIPIN (PLIN) LOCUS IS ASSOCIATED WITH OBESITY-RELATED PHENOTYPES IN WHITE WOMEN  

Technology Transfer Automated Retrieval System (TEKTRAN)

Perilipin coats intracellular lipid droplets and modulates adipocyte lipolysis. We have evaluated the association between several polymorphisms at the perilipin (PLIN) locus (PLIN1:6209T>C; PLIN4:11482G>A; PLIN5:13041A>G and PLIN6:14995A>T) with obesity-related phenotypes in 1589 White subjects rand...

245

Behaviour plasticity without learning: phenotypic and genetic variation of na??ve Daphnia in an ecological trade-off  

Microsoft Academic Search

The swimming behaviour of adult Daphnia largely governs their depth, which has a direct effect on both individual foraging success and predation avoidance. We treated individual swimming behaviour as a threshold character and used directional changes in average clonal depth within experimental tubes as a test for character plasticity. We compared the swimming behaviours of two cohabiting, phenotypically similar Daphnia

Gray Stirling; Derek A. Roff

2000-01-01

246

Tooth agenesis patterns and phenotype variation in a cohort of Belgian patients with hypodontia and oligodontia clustered in 79 families with their pedigrees.  

PubMed

BACKGROUND:Even though tooth agenesis is the most common developmental anomaly of the human dentition, its genetic background and pathogenic mechanism(s) still remain poorly understood. Syndromic and isolated forms of hypodontia have been described and can occur sporadically or in families.Objectives:We describe and analyse the hypo-/oligodontia phenotype variations in families. The index patient suffers from severe or mild hypodontia; case-parents/sib records are available. Furthermore, we aim to evaluate whether the different agenesis patterns in the pedigrees are predictive of mutations in specific genes based on reported genotype-phenotype associations.Materials and methods:Dental records and pedigrees were collected from 79 families. In 67 families, the index patient presented with oligodontia while in 12 families with hypodontia. The phenotype data of 66 oligodontia index patients were analysed with the Tooth Agenesis Code software.Results:Nine families counted two members; one family counted three members affected with oligodontia. Twenty-four oligodontia families respectively had one (n = 17), two (n = 4), three (n = 2) or four (n = 1) additional family members presenting with hypodontia. Of the 77 oligodontia cases, two showed the same tooth agenesis pattern, while 75 patients showed unique tooth agenesis patterns.Conclusions:Despite familial aggregation and expected Mendelian segregation, the number of missing teeth in the familial hypo-/oligodontia phenotypes and the tooth agenesis patterns are highly variable between the affected family members. Therefore, we hypothesize that tooth agenesis is not (always) a simple monogenic condition, but additional genetic or environmental factors can modify the expression of the phenotype. PMID:23598609

Dreesen, Karoline; Swinnen, Steven; Devriendt, Koenraad; Carels, Carine

2013-04-18

247

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

2011-12-08

248

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

249

Quantitative Genetic Variation of Enzyme Activities in Natural Populations of Drosophila melanogaster  

Microsoft Academic Search

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

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

1980-01-01

250

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

2011-10-24

251

Correlation between Anolis lizard dewlap phenotype and environmental variation indicates adaptive divergence of a signal important to sexual selection and species recognition.  

PubMed

Although the importance of signals involved in species recognition and sexual selection to speciation is widely recognized, the processes that underlie signal divergence are still a matter of debate. Several possible processes have been hypothesized, including genetic drift, arbitrary sexual selection, and adaptation to local signaling environments. We use comparative analyses to investigate whether the remarkable geographic variation of dewlap phenotype in a Hispaniolan trunk Anolis lizard (A. distichus) is a result of adaptive signal divergence to heterogeneous environments. We recover a repeated pattern of divergence in A. distichus dewlap color, pattern, and size with environmental variation across Hispaniola. These results are aligned with ecological models of signal divergence and provide strong evidence for dewlap adaptation to local signaling environments. We also find that A. distichus dewlaps vary with the environment in a different manner to other previously studied anoles, thus expanding upon previous predictions on the direction dewlaps will diverge in perceptual color space in response to the environment. PMID:23356628

Ng, Julienne; Landeen, Emily L; Logsdon, Ryane M; Glor, Richard E

2012-10-10

252

[Intermediate phenotype of schizophrenia].  

PubMed

Genes are major contributors to schizophrenia. The intermediate phenotype concept represents a strategy for identifying risk genes for schizophrenia and for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in schizophrenia. Intermediate phenotypes are defined by being heritable, being able to measure quantitatively; being related to the disorder and its symptoms in the general population; being stable over time; showing increased expression in unaffected relatives of probands; and cosegregation with the disorder in families. Intermediate phenotypes in schizophrenia are neurocognition, neuroimaging, neurophysiology, etc. In this review, we present concept, recent work, and future perspective of intermediate phenotype. PMID:23678587

Hashimoto, Ryota

2013-04-01

253

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

NASA Astrophysics Data System (ADS)

When small RNAs are loaded onto Argonaute proteins they can form the RNA-induced silencing complexes (RISCs), which mediate RNA interference. RISC-formation is dependent on a shared pool of Argonaute proteins and RISC loading factors, and is thus susceptible to competition among small RNAs for loading. We present a mathematical model that aims to understand how small RNA competition for the PTR resources affects target gene repression. We discuss that small RNA activity is limited by RISC-formation, RISC-degradation and the availability of Argonautes. Together, these observations explain a number of PTR saturation effects encountered experimentally. We show that different competition conditions for RISC-loading result in different signatures of PTR activity determined also by the amount of RISC-recycling taking place. In particular, we find that the small RNAs less efficient at RISC-formation, using fewer resources of the PTR pathway, can perform in the low RISC-recycling range equally well as their more effective counterparts. Additionally, we predict a novel signature of PTR in target expression levels. 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 which can be used in order to infer from experimental data the particular characteristics of underlying PTR activity.

Klironomos, Filippos D.; Berg, Johannes

2013-02-01

254

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

2011-11-27

255

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

PubMed

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

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

2012-11-15

256

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

257

Spatial and temporal variation in the kdr allele L1014S in Anopheles gambiae s.s. and phenotypic variability in susceptibility to insecticides in Western Kenya  

PubMed Central

Background Malaria vector control in Africa depends upon effective insecticides in bed nets and indoor residual sprays. This study investigated the extent of insecticide resistance in Anopheles gambiae s.l., Anopheles gambiae s.s. and Anopheles arabiensis in western Kenya where ownership of insecticide-treated bed nets has risen steadily from the late 1990s to 2010. Temporal and spatial variation in the frequency of a knock down resistance (kdr) allele in A. gambiae s.s. was quantified, as was variation in phenotypic resistance among geographic populations of A. gambiae s.l. Methods To investigate temporal variation in kdr frequency, individual specimens of A. gambiae s.s. from two sentinel sites were genotyped using RT-PCR from 1996-2010. Spatial variation in kdr frequency, species composition, and resistance status were investigated in additional populations of A. gambiae s.l. sampled in western Kenya in 2009 and 2010. Specimens were genotyped for kdr as above and identified to species via conventional PCR. Field-collected larvae were reared to adulthood and tested for insecticide resistance using WHO bioassays. Results Anopheles gambiae s.s. showed a dramatic increase in kdr frequency from 1996 - 2010, coincident with the scale up of insecticide-treated nets. By 2009-2010, the kdr L1014S allele was nearly fixed in the A. gambiae s.s. population, but was absent in A. arabiensis. Near Lake Victoria, A. arabiensis was dominant in samples, while at sites north of the lake A. gambiae s.s was more common but declined relative to A. arabiensis from 2009 to 2010. Bioassays demonstrated that A. gambiae s.s. had moderate phenotypic levels of resistance to DDT, permethrin and deltamethrin while A. arabiensis was susceptible to all insecticides tested. Conclusions The kdr L1014S allele has approached fixation in A. gambiae s.s. populations of western Kenya, and these same populations exhibit varying degrees of phenotypic resistance to DDT and pyrethroid insecticides. The near absence of A. gambiae s.s. from populations along the lakeshore and the apparent decline in other populations suggest that insecticide-treated nets remain effective against this mosquito despite the increase in kdr allele frequency. The persistence of A. arabiensis, despite little or no detectable insecticide resistance, is likely due to behavioural traits such as outdoor feeding and/or feeding on non-human hosts by which this species avoids interaction with insecticide-treated nets.

2011-01-01

258

Quantitative Analysis of Age Specific Variation in the Abundance of Human Female Parotid Salivary Proteins  

PubMed Central

Summary Human saliva is a protein-rich, easily accessible source of potential local and systemic biomarkers to monitor changes that occur under pathological conditions; however little is known about the changes in abundance associated with normal aging. In this study, we performed a comprehensive proteomic profiling of pooled saliva collected from the parotid glands of healthy female subjects, divided into two age groups 1 and 2 (20–30 and 55–65 years old, respectively). Hydrophobic charge interaction chromatography was used to separate high from low abundant proteins prior to characterization of the parotid saliva using multidimensional protein identification technology (MudPIT). Collectively, 532 proteins were identified in the two age groups. Of these proteins, 266 were identified exclusively in one age group, while 266 proteins were common to both groups. The majority of the proteins identified in the two age groups belonged to the defense and immune response category. Of note, several defense related proteins (e.g. lysozyme, lactoferrin and histatin-1) were significantly more abundant in group 2 as determined by G-test. Selected representative mass spectrometric findings were validated by western blot analysis. Our study reports the first quantitative analysis of differentially regulated proteins in ductal saliva collected from young and older female subjects. This study supports the use of high-throughput proteomics as a robust discovery tool. Such results provide a foundation for future studies to identify specific salivary proteins which may be linked to age-related diseases specific to women.

Ambatipudi, Kiran S.; Lu, Bingwen; Hagen, Fred K; Melvin, James E.; Yates, John R.

2010-01-01

259

Estimation of relative binding free energy based on a free energy variational principle for quantitative structure activity relationship analyses  

NASA Astrophysics Data System (ADS)

In the present study, we try to estimate values of relative binding free energy of ligands to a protein based on a free energy variational principle. Results are used for quantitative structure activity relationship (QSAR) analyses. The aim of our study is to construct a procedure free from adjustable empirical parameters and expensive computational costs, and fast enough for use in QSAR. We apply our procedure to inhibitors of dehydrofolate reductase for which values of binding free energy have been studied extensively with both experimental and theoretical techniques. We demonstrate in this paper that we can obtain fairly good values when we can categorize ligands based on structural similarity or on the Log P values of substituents. The present results indicate that our procedure is valid and applicable to QSAR analyses for drug discovery when major differences in ligand structures can be regarded as small perturbations.

Shine, Yuichi; Kikuchi, Takeshi

2009-11-01

260

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

SciTech Connect

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

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

1996-03-01

261

Phenotypic differentiation in female preference related to geographic variation in male predation risk in the Trinidad guppy ( Poecilia reticulata )  

Microsoft Academic Search

Populations of the Trinidad guppy range from areas with high levels of predation by other species of fish to areas with little or no piscine predation. Previous studies have shown that variation among populations in male coloration can be explained by a balance between female preference for brighter males and natural selection against bright males. High levels of male courtship

Gregory Stoner; Felix Breden

1988-01-01

262

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

Microsoft Academic Search

The PB River basin of northern Italy is the home of distinctive and endemic morphologi- cal 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

E. GIUFFRA; L. BERNATCHEZ; R. GUYOMARD

1994-01-01

263

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

264

Genome-wide quantitative assessment of variation in DNA methylation patterns  

PubMed Central

Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.

Xie, Hehuang; Wang, Min; de Andrade, Alexandre; de F. Bonaldo, Maria; Galat, Vasil; Arndt, Kelly; Rajaram, Veena; Goldman, Stewart; Tomita, Tadanori; Soares, Marcelo B.

2011-01-01

265

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

266

Quantitative autism traits in first degree relatives: evidence for the broader autism phenotype in fathers, but not in mothers and siblings.  

PubMed

Autism spectrum disorder (ASD) symptoms are present in unaffected relatives and individuals from the general population. Results are inconclusive, however, on whether unaffected relatives have higher levels of quantitative autism traits (QAT) or not. This might be due to differences in research populations, because behavioral data and molecular genetic research suggest that the genetic etiology of ASD is different in multiplex and simplex families. We compared 117 unaffected siblings and 276 parents of at least one child with ASD with 280 children and 595 adults from the general population on the presence of QAT using the Social Responsiveness Scale (SRS). Mean SRS scores for siblings, control children, parents and control adults were 25.4, 26.6, 33.7 and 32.9. Fathers of children with ASD showed significantly higher levels of QAT than controls, but siblings and mothers did not. We could not detect a statistically significant difference in SRS scores between relatives from simplex and multiplex families. These results do not support the theory of differential (genetic) etiology in multiplex and simplex families and suggest that a carried genetic risk is generally not expressed phenotypically in most relatives, except in fathers. PMID:21949002

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

2011-09-26

267

Quantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders suggests a correlation between phenotypic severity and Smad signaling activity.  

PubMed

Mutations in the gene encoding transforming growth factor-beta receptor type II (TGFBR2) have been described in patients with Loeys-Dietz syndrome (LDS), Marfan syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections (TAAD). Here, we present a comprehensive and quantitative analysis of TGFBR2 expression, turnover and TGF-?-induced Smad and ERK signaling activity for nine mutations identified in patients with LDS, MFS2 and TAAD. The mutations had different effects on protein stability, internalization and signaling. A dominant-negative effect was demonstrated for mutations associated with LDS and MFS2. No mutation showed evidence of an immediate cell-autonomous paradoxical activation of TGF-? signaling. There were no cell biological differences between mutations described in patients with LDS and MFS2. By contrast, R460C, which has been found in familial TAAD but not in MFS2 or LDS, showed a less-severe dominant-negative effect and retained residual Smad phosphorylation and transcriptional activity. TAAD is characterized primarily by thoracic aortic aneurysms or dissections. By contrast, MFS2 is characterized by numerous skeletal abnormalities, and patients with LDS additionally can display craniofacial and other abnormalities. Therefore, our findings suggest that the balance between defects in Smad and ERK signaling might be an important determinant of phenotypic severity in disorders related to mutations in TGFBR2. PMID:21098638

Horbelt, Daniel; Guo, Gao; Robinson, Peter N; Knaus, Petra

2010-11-23

268

Association of trait-defined, eating-disorder sub-phenotypes with (biallelic and triallelic) 5HTTLPR variations  

Microsoft Academic Search

ContextEfforts to classify eating-disordered individuals based on concurrent personality traits have consistently converged on a typology encompassing “over-regulated”, “dysregulated”, and “low psychopathology” subgroups. In various populations, evidence has associated personality variations of an “over-regulated\\/dysregulated” type with differences on serotonin-system indices, and specifically, with different loadings of serotonin transporter promoter regulatory region polymorphism (5HTTLPR) genotypes and alleles. We explored the extent

Howard Steiger; Jodie Richardson; Norbert Schmitz; Ridha Joober; Mimi Israel; Kenneth R. Bruce; Lise Gauvin; Cathy Dandurand; Annelie Anestin

2009-01-01

269

Exploiting natural variation in Arabidopsis.  

PubMed

Natural variation for many traits is present within the species Arabidopsis thaliana. This chapter describes the use of natural variation to elucidate genes underlying the regulation of quantitative traits. It deals with the development and use of mapping populations, the detection and handling of genetic markers, the phenotyping of quantitative traits, and, finally, QTL analyses. The focus of the chapter is on the use and development of recombinant inbred lines, but other types of segregating populations, including genome-wide association mapping in natural populations, are also discussed. PMID:24057363

Molenaar, Johanna A; Keurentjes, Joost J B

2014-01-01

270

Phenotypic plasticity in Passiflora suberosa L.(Passifloraceae): induction and reversion of two morphs by variation in light intensity.  

PubMed

Leaf morphology may vary considerably even within a branch of Passiflora suberosa plants. Leaves are of a typical green type in shaded areas, but in open fields turn into violet, and apparently have greater thickness and trichome density. The proximate causes and the adaptive meaning, if any, for the existence of the violet morph are still unknown. By cultivating P. suberosa clones under two light regimes (total and partial exposure to sunlight), we consecutively induced (first year) and then reversed (second year) the appearance of the violet morph. We evaluated the corresponding changes in morpho-anatomic and chemical leaf characteristics. Plants that were grown under partial sunlight had a greater size and did not alter their green color, but those grown under total sunlight changed into violet, were smaller in size and their leaves were tougher, thicker, and had a greater number of trichomes. The violet morph had increased anthocyanins and phenolic derivatives. It also showed cellular hypertrophy, a greater number of cell layers in the mesophyll, and a lignified pericycle. Since these morphs are interchangeable by changing light conditions, we inferred that they are not determined by genotypic diversity, but are mainly a result of a physiological response to light stress, and thus part of P. suberosa phenotypic plasticity. PMID:17119833

Barp, E A; Soares, G L G; Gosmann, G; Machado, A M; Vecchi, C; Moreira, G R P

2006-08-01

271

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

PubMed

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

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

2011-06-29

272

Quantitative trait loci for variation in immune response to a Foot-and-Mouth Disease virus peptide  

PubMed Central

Background Infectious disease of livestock continues to be a cause of substantial economic loss and has adverse welfare consequences in both the developing and developed world. New solutions to control disease are needed and research focused on the genetic loci determining variation in immune-related traits has the potential to deliver solutions. However, identifying selectable markers and the causal genes involved in disease resistance and vaccine response is not straightforward. The aims of this study were to locate regions of the bovine genome that control the immune response post immunisation. 195 F2 and backcross Holstein Charolais cattle were immunised with a 40-mer peptide derived from foot-and-mouth disease virus (FMDV). T cell and antibody (IgG1 and IgG2) responses were measured at several time points post immunisation. All experimental animals (F0, F1 and F2, n = 982) were genotyped with 165 microsatellite markers for the genome scan. Results Considerable variability in the immune responses across time was observed and sire, dam and age had significant effects on responses at specific time points. There were significant correlations within traits across time, and between IgG1 and IgG2 traits, also some weak correlations were detected between T cell and IgG2 responses. The whole genome scan detected 77 quantitative trait loci (QTL), on 22 chromosomes, including clusters of QTL on BTA 4, 5, 6, 20, 23 and 25. Two QTL reached 5% genome wide significance (on BTA 6 and 24) and one on BTA 20 reached 1% genome wide significance. Conclusions A proportion of the variance in the T cell and antibody response post immunisation with an FDMV peptide has a genetic component. Even though the antigen was relatively simple, the humoral and cell mediated responses were clearly under complex genetic control, with the majority of QTL located outside the MHC locus. The results suggest that there may be specific genes or loci that impact on variation in both the primary and secondary immune responses, whereas other loci may be specifically important for early or later phases of the immune response. Future fine mapping of the QTL clusters identified has the potential to reveal the causal variations underlying the variation in immune response observed.

2010-01-01

273

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

PubMed Central

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

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

2010-01-01

274

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

PubMed

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

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

2010-09-01

275

Biological variation and quality control of plasma human immunodeficiency virus type 1 RNA quantitation by reverse transcriptase polymerase chain reaction.  

PubMed Central

Quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in the plasma of seropositive individuals was performed by using an external control assay with techniques to standardize and control each measurement. Rigorous study of the variability of the assay showed that the median intraassay reproducibility was log10 0.15 RNA copies per ml of plasma, while the median interassay reproducibility on replicate plasma samples was log10 0.25 copies perml. Specimen stability studies showed reproducible recovery of RNA from plasma stored at -70 degrees C for up to 12 months. In clinically stable patients who were either untreated or taking zidovudine, the average week-to-week variation in plasma RNA levels, measured in real time, was log10 0.30 RNA copies per ml. In contrast, patients either initiating or changing antiretroviral therapy showed a fall of log10 0.8 to log10 2.0 copies per ml in plasma RNA levels. Overall, 105 of 110 (96%) HIV-1-seropositive individuals with CD4 counts of 36 to 868 cells per mm3 had quantifiable HIV-1 RNA over a range of log10 2.70 to log10 6.23 RNA copies per ml, including 81% (13 of 16) of the individuals with greater than 500 CD4 cells per mm3. Accurate and reproducible quantitation of plasma viremia in real time by reverse transcriptase polymerase chain reaction, particularly in asymptomatic HIV-1-infected individuals with high CD4 counts, provides a basis for the use of this virologic measure to monitor the short- and long-term effects of early intervention therapeutic strategies on viral burden.

Winters, M A; Tan, L B; Katzenstein, D A; Merigan, T C

1993-01-01

276

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

2013-02-26

277

Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?  

PubMed

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. PMID:20976194

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

2010-10-14

278

Biofilm-grown Mycoplasma mycoides subsp. mycoides SC exhibit both phenotypic and genotypic variation compared with planktonic cells.  

PubMed

Biofilm formation where bacterial cells adhere to a surface and surround themselves in a polysaccharide matrix is thought to be an important factor in disease initiation and persistence for many bacterial species. We have examined biofilm formation by Mycoplasma mycoides subsp. mycoides small colony using a simple model without an air/liquid interface and have found that adherent Mmm SC was more resistant to many stresses, including heat, osmotic shock and oxidative stress. Biofilms of Mmm SC also exhibited remarkable persistence and were able to survive for up to 20 weeks in stationary phase. Significant variation was seen between Mmm SC strains in their ability to form a biofilm and the morphology of the biofilm produced with some strains unable to produce microcolonies. Proteomic analysis found that a number of proteins linked to adherence were over-expressed in biofilms compared with planktonic cells. PMID:18191921

McAuliffe, Laura; Ayling, Roger D; Ellis, Richard J; Nicholas, Robin A J

2007-12-04

279

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

280

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

PubMed

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. PMID:15657762

Blums, Peter; Nichols, James D; Hines, James E; Lindberg, Mark S; Mednis, Aivars

2005-01-19

281

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

282

Genomic Analysis of QTLs and Genes Altering Natural Variation in Stochastic Noise  

Microsoft Academic Search

Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype. While most studies have focused on genetic determinants of phenotypic average, it is rapidly becoming understood that stochastic noise is genetically determined. However, it is not known how many traits display genetic control of stochastic noise nor how broadly these stochastic

Jose M. Jimenez-Gomez; Jason A. Corwin; Bindu Joseph; Julin N. Maloof; Daniel J. Kliebenstein

2011-01-01

283

Test of candidate gene–quantitative trait locus association applied to fatness in mice  

Microsoft Academic Search

We test for the contribution of five strong candidate genes for obesity to quantitative variation for fatness in mice. The candidate loci are known through their major mutant phenotypes. We propose a randomization test for overall contribution of candidate genes, based on the empirical distribution of LOD scores from a quantitative trait locus (QTL) genome scan. The test is applied

VICTORIA M. FALCONER; Peter D Keightley

1998-01-01

284

Quantitative Label-Free Proteomics for Discovery of Biomarkers in Cerebrospinal Fluid: Assessment of Technical and Inter-Individual Variation  

PubMed Central

Background Biomarkers are required for pre-symptomatic diagnosis, treatment, and monitoring of neurodegenerative diseases such as Alzheimer's disease. Cerebrospinal fluid (CSF) is a favored source because its proteome reflects the composition of the brain. Ideal biomarkers have low technical and inter-individual variability (subject variance) among control subjects to minimize overlaps between clinical groups. This study evaluates a process of multi-affinity fractionation (MAF) and quantitative label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) for CSF biomarker discovery by (1) identifying reparable sources of technical variability, (2) assessing subject variance and residual technical variability for numerous CSF proteins, and (3) testing its ability to segregate samples on the basis of desired biomarker characteristics. Methods/Results Fourteen aliquots of pooled CSF and two aliquots from six cognitively normal individuals were randomized, enriched for low-abundance proteins by MAF, digested endoproteolytically, randomized again, and analyzed by nano-LC-MS. Nano-LC-MS data were time and m/z aligned across samples for relative peptide quantification. Among 11,433 aligned charge groups, 1360 relatively abundant ones were annotated by MS2, yielding 823 unique peptides. Analyses, including Pearson correlations of annotated LC-MS ion chromatograms, performed for all pairwise sample comparisons, identified several sources of technical variability: i) incomplete MAF and keratins; ii) globally- or segmentally-decreased ion current in isolated LC-MS analyses; and iii) oxidized methionine-containing peptides. Exclusion of these sources yielded 609 peptides representing 81 proteins. Most of these proteins showed very low coefficients of variation (CV<5%) whether they were quantified from the mean of all or only the 2 most-abundant peptides. Unsupervised clustering, using only 24 proteins selected for high subject variance, yielded perfect segregation of pooled and individual samples. Conclusions Quantitative label-free LC-MS/MS can measure scores of CSF proteins with low technical variability and can segregate samples according to desired criteria. Thus, this technique shows potential for biomarker discovery for neurological diseases.

Malone, James P.; Gilmore, Petra; Davis, Alan E.; Xiong, Chengjie; Fagan, Anne M.; Townsend, R. Reid; Holtzman, David M.

2013-01-01

285

Quantifying genetic variations and phenotypic plasticity of leaf phenology and growth for two temperate Fagaceae species (sessile oak and european beech)  

NASA Astrophysics Data System (ADS)

Under current climate change, research on inherent adaptive capacities of organisms is crucial to assess future evolutionary changes of natural populations. Genetic diversity and phenotypic plasticity constitute adaptative capacities that could allow populations to respond to new environmental conditions. The aim of the present study was (i) to determine whether there are genetic variations among populations from altitudinal gradients using a lowland common garden experiment and (ii) to assess the magnitude of phenotypic plasticity using a reciprocal transplant experiment (5 elevations from 100 to 1600 m asl.) for leaf phenology (flushing and senescence) and growth of two fagaceae species (Fagus sylvatica and Quercus petraea). We found significant differences in phenology among provenances for most species, and evidenced that these among-population differences in phenology were related to annual temperature of the provenance sites for both species. It's noteworthy that, along the same climatic gradient, the species exhibited opposite genetic clines: beech populations from high elevation flushed earlier than those of low elevation, whereas we observed an opposite trend for oak. Finally, we highlighted that both phenology timing and growth rate were highly consistent year to year. The results demonstrated that in spite of the proximity of the populations in their natural area, altitude led to genetic differentiations in their phenology and growth. Moreover, a high phenological plasticity was found for both species. We evidenced that reaction norms of flushing timing to temperature followed linear clinal trends for both species with an average shift of 5.7 days per degree increase. Timing of leaf senescence exhibited hyperbolic trends for beech and no or slight trends for oak. Furthermore, within species, there was no difference in magnitude of phenological plasticity among populations neither for flushing, nor for senescence. Consequently, for both species, the growing season length increased to reach maximum values for annual temperature ranging from 10°C to 13°C according to the population. These adaptive capacities (genetic differentiations and high magnitude of plasticity) could allow populations to respond immediately to temperature variations in term of leaf phenology and then to cope with current climate change. Finally, we also highlight that current populations tend to occupy suboptimal environments, i.e, populations inhabit climates colder that their optimum.

Delzon, Sylvain; Vitasse, Yann; Alberto, Florian; Bresson, Caroline; Kremer, Antoine

2010-05-01

286

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

PubMed Central

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

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

2013-01-01

287

The distribution and 'in vivo' phase variation status of haemoglobin receptors in invasive meningococcal serogroup B disease: genotypic and phenotypic analysis.  

PubMed

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

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

2013-09-30

288

Novel temporal, fine-scale and growth variation phenotypes in roots of adult-stage maize (Zea mays L.) in response to low nitrogen stress.  

PubMed

There is interest in discovering root traits associated with acclimation to nutrient stress. Large root systems, such as in adult maize, have proven difficult to be phenotyped comprehensively and over time, causing target traits to be missed. These challenges were overcome here using aeroponics, a system where roots grow in the air misted with a nutrient solution. Applying an agriculturally relevant degree of low nitrogen (LN) stress, 30-day-old plants responded by increasing lengths of individual crown roots (CRs) by 63%, compensated by a 40% decline in CR number. LN increased the CR elongation rate rather than lengthening the duration of CR growth. Only younger CR were significantly responsive to LN stress, a novel finding. LN shifted the root system architectural balance, increasing the lateral root (LR)-to-CR ratio, adding ?70 m to LR length. LN caused a dramatic increase in second-order LR density, not previously reported in adult maize. Despite the near-uniform aeroponics environment, LN induced increased variation in the relative lengths of opposing LR pairs. Large-scale analysis of root hairs (RHs) showed that LN decreased RH length and density. Time-course experiments suggested the RH responses may be indirect consequences of decreased biomass/demand under LN. These results identify novel root traits for genetic dissection. PMID:21848860

Gaudin, Amelie C M; McClymont, Sarah A; Holmes, Bridget M; Lyons, Eric; Raizada, Manish N

2011-09-12

289

Complex genetic interactions in a quantitative trait locus.  

PubMed

Whether in natural populations or between two unrelated members of a species, most phenotypic variation is quantitative. To analyze such quantitative traits, one must first map the underlying quantitative trait loci. Next, and far more difficult, one must identify the quantitative trait genes (QTGs), characterize QTG interactions, and identify the phenotypically relevant polymorphisms to determine how QTGs contribute to phenotype. In this work, we analyzed three Saccharomyces cerevisiae high-temperature growth (Htg) QTGs (MKT1, END3, and RHO2). We observed a high level of genetic interactions among QTGs and strain background. Interestingly, while the MKT1 and END3 coding polymorphisms contribute to phenotype, it is the RHO2 3'UTR polymorphisms that are phenotypically relevant. Reciprocal hemizygosity analysis of the Htg QTGs in hybrids between S288c and ten unrelated S. cerevisiae strains reveals that the contributions of the Htg QTGs are not conserved in nine other hybrids, which has implications for QTG identification by marker-trait association. Our findings demonstrate the variety and complexity of QTG contributions to phenotype, the impact of genetic background, and the value of quantitative genetic studies in S. cerevisiae. PMID:16462944

Sinha, Himanshu; Nicholson, Bradly P; Steinmetz, Lars M; McCusker, John H

2006-02-03

290

Next Generation Quantitative Genetics in Plants  

PubMed Central

Most characteristics in living organisms show continuous variation, which suggests that they are controlled by multiple genes. Quantitative trait loci (QTL) analysis can identify the genes underlying continuous traits by establishing associations between genetic markers and observed phenotypic variation in a segregating population. The new high-throughput sequencing (HTS) technologies greatly facilitate QTL analysis by providing genetic markers at genome-wide resolution in any species without previous knowledge of its genome. In addition HTS serves to quantify molecular phenotypes, which aids to identify the loci responsible for QTLs and to understand the mechanisms underlying diversity. The constant improvements in price, experimental protocols, computational pipelines, and statistical frameworks are making feasible the use of HTS for any research group interested in quantitative genetics. In this review I discuss the application of HTS for molecular marker discovery, population genotyping, and expression profiling in QTL analysis.

Jimenez-Gomez, Jose M.

2011-01-01

291

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

Microsoft Academic Search

Evolutionary biologists seek to understand the genetic basis for multivariate phenotypic divergence. We constructed an F2 mapping population (N ¼ 539) between two distinct populations of Mimulus guttatus .W e 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,

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

2005-01-01

292

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

293

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

Microsoft Academic Search

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

Eyal Fridman; Tzili Pleban; Dani Zamir

2000-01-01

294

Phenotypic Differences between Pediatric and Adult Asthma  

Microsoft Academic Search

The goal of asthma phenotyping is to understand disease mecha- nisms or optimize management. Phenotypes show age-related variation. The phenotypes of wheezing in the first year of life are little studied; many remit in the second year of life, and the children who remit do not have later-onset wheeze, as far as is known. Preschool wheeze is optimally phenotyped by

Andrew Bush; Andrew Menzies-Gow

2009-01-01

295

Phenotypic switching in bacteria  

NASA Astrophysics Data System (ADS)

Living matter is a non-equilibrium system in which many components work in parallel to perpetuate themselves through a fluctuating environment. Physiological states or functionalities revealed by a particular environment are called phenotypes. Transitions between phenotypes may occur either spontaneously or via interaction with the environment. Even in the same environment, genetically identical bacteria can exhibit different phenotypes of a continuous or discrete nature. In this thesis, we pursued three lines of investigation into discrete phenotypic heterogeneity in bacterial populations: the quantitative characterization of the so-called bacterial persistence, a theoretical model of phenotypic switching based on those measurements, and the design of artificial genetic networks which implement this model. Persistence is the phenotype of a subpopulation of bacteria with a reduced sensitivity to antibiotics. We developed a microfluidic apparatus, which allowed us to monitor the growth rates of individual cells while applying repeated cycles of antibiotic treatments. We were able to identify distinct phenotypes (normal and persistent) and characterize the stochastic transitions between them. We also found that phenotypic heterogeneity was present prior to any environmental cue such as antibiotic exposure. Motivated by the experiments with persisters, we formulated a theoretical model describing the dynamic behavior of several discrete phenotypes in a periodically varying environment. This theoretical framework allowed us to quantitatively predict the fitness of dynamic populations and to compare survival strategies according to environmental time-symmetries. These calculations suggested that persistence is a strategy used by bacterial populations to adapt to fluctuating environments. Knowledge of the phenotypic transition rates for persistence may provide statistical information about the typical environments of bacteria. We also describe a design of artificial genetic networks that would implement a more general theoretical model of phenotypic switching. We will use a new cloning strategy in order to systematically assemble a large number of genetic features, such as site-specific recombination components from the R64 plasmid, which invert several coexisting DNA segments. The inversion of these segments would lead to discrete phenotypic transitions inside a living cell. These artificial phenotypic switches can be controlled precisely in experiments and may serve as a benchmark for their natural counterparts.

Merrin, Jack

296

Genotype-Environment Interactions and the Maintenance of Polygenic Variation  

Microsoft Academic Search

Genotype-environment interactions may be a potent force maintaining genetic variation in quantitative traits in natural populations. This is shown by a simple model of additive polygenic inheritance in which the additive contributions of alleles vary with the environment. Under simplifying symmetry assumptions, the model implies that the variance of the phenotypes produced across environments by a multilocus genotype decreases as

John H. Gillespie; Michael Turelli

1989-01-01

297

Quantitative genetic analysis of among-population variation in sperm and female sperm-storage organ length in Drosophila mojavensis  

Microsoft Academic Search

Summary In Drosophila, sperm length and the length of the females' primary sperm-storage organ have rapidly coevolved through post-copulatory sexual selection. This pattern is evident even among geographic populations of Drosophila mojavensis. To understand better these traits of potential importance for speciation, we performed quantitative genetic analysis of both seminal receptacle length and sperm length in two divergent populations. Parental

GARY T. MILLER; WILLIAM T. STARMER; SCOTT PITNICK

2003-01-01

298

Abdominal Waggings and Variation of Their Rate of Occurrence in the Social Wasp, Polistes dominulus Christ. I. Quantitative Analysis  

Microsoft Academic Search

The quantitative study of abdominal waggings in Polistes dominulus Christ, covering a total of 16,000 sequences of movements observed in 13 colonies (mono- and polygyne), showed or confirmed the following points. The same form of abdominal wagging, very frequent in this species, is carried out by foundresses in two contexts: when they are caring for their brood and during aggressive

C. Brillet; S. Semenoff Tian-Chansky; Y. Le Conte

1999-01-01

299

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

Microsoft Academic Search

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

Roff; Mousseau

1999-01-01

300

Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2  

PubMed Central

Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2. The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4–V6 and LQT1 morphology in leads V1–V2. Genomic DNA was isolated from lymphocytes. All exons and intron borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed patch-clamp analysis. In addition, WT or K897T Kv11.1 were also studied by patch clamp. Current–voltage (I-V) relations for V110I showed a significant reduction in both developing and tail current densities compared to WT at potentials >+20 mV (p < 0.05; n = 8 cells, each group), suggesting a reduction in IKs currents. K897T- Kv11.1 channels displayed a significantly reduced tail current density compared with WT-Kv11.1 at potentials >+10 mV. Interestingly, channel availability assessed using a triple-pulse protocol was slightly greater for K897T compared with WT (V0.5 = ?53.1 ± 1.13 mV and ?60.7 ± 1.15 mV for K897T and WT, respectively; p < 0.05). Comparison of the fully activated I-V revealed no difference in the rectification properties between WT and K897T channels. We report a patient with a loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest that a reduction of both IKr and IKs underlies the combined LQT1 and LQT2 phenotype observed in this patient.

Cordeiro, Jonathan M.; Perez, Guillermo J.; Schmitt, Nicole; Pfeiffer, Ryan; Nesterenko, Vladislav V.; Burashnikov, Elena; Veltmann, Christian; Borggrefe, Martin; Wolpert, Christian; Schimpf, Rainer; Antzelevitch, Charles

2010-01-01

301

Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2.  

PubMed

Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2. The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4-V6 and LQT1 morphology in leads V1-V2. Genomic DNA was isolated from lymphocytes. All exons and intron borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed patch-clamp analysis. In addition, WT or K897T Kv11.1 were also studied by patch clamp. Current-voltage (I-V) relations for V110I showed a significant reduction in both developing and tail current densities compared with WT at potentials >+20 mV (p < 0.05; n = 8 cells, each group), suggesting a reduction in IKs currents. K897T- Kv11.1 channels displayed a significantly reduced tail current density compared with WT-Kv11.1 at potentials >+10 mV. Interestingly, channel availability assessed using a triple-pulse protocol was slightly greater for K897T compared with WT (V0.5 = -53.1 ± 1.13 mV and -60.7 ± 1.15 mV for K897T and WT, respectively; p < 0.05). Comparison of the fully activated I-V revealed no difference in the rectification properties between WT and K897T channels. We report a patient with a loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest that a reduction of both IKr and IKs underlies the combined LQT1 and LQT2 phenotype observed in this patient. PMID:21164565

Cordeiro, Jonathan M; Perez, Guillermo J; Schmitt, Nicole; Pfeiffer, Ryan; Nesterenko, Vladislav V; Burashnikov, Elena; Veltmann, Christian; Borggrefe, Martin; Wolpert, Christian; Schimpf, Rainer; Antzelevitch, Charles

2010-12-01

302

Quantitative autism traits in first degree relatives: evidence for the broader autism phenotype in fathers, but not in mothers and siblings  

Microsoft Academic Search

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

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

2012-01-01

303

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

Microsoft Academic Search

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

Youzuo Lin; Lianjie Huang; Zhigang Zhang

2011-01-01

304

Variations in quantitative and qualitative characteristics of wild marigold ( Tagetes minuta L.) oils distilled under vacuum and at NTP  

Microsoft Academic Search

Essential oil of Tagetes minuta was distilled in vacuo in a mini distillation apparatus to study and compare the qualitative and quantitative characteristics vis-à-vis oil distilled by conventional distillation technique at normal temperature and pressure (NTP), which revealed that higher oil yield (1.56%) was obtained in the oil distilled by conventional distillation technique at NTP and decreased gradually with increase

Kiran G. D. Babu; V. K. Kaul

2007-01-01

305

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

306

Quantitative trait loci for variation in immune response to a Foot-and-Mouth Disease virus peptide  

Microsoft Academic Search

BACKGROUND: Infectious disease of livestock continues to be a cause of substantial economic loss and has adverse welfare consequences in both the developing and developed world. New solutions to control disease are needed and research focused on the genetic loci determining variation in immune-related traits has the potential to deliver solutions. However, identifying selectable markers and the causal genes involved

Richard J Leach; Susan C Craigmile; Sara A Knott; John L Williams; Elizabeth J Glass

2010-01-01

307

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

Microsoft Academic Search

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

McCutchen-Maloney; Sandra L

2002-01-01

308

A dynamic framework for quantifying the genetic architecture of phenotypic plasticity.  

PubMed

Despite its central role in the adaptation and microevolution of traits, the genetic architecture of phenotypic plasticity, i.e. multiple phenotypes produced by a single genotype in changing environments, remains elusive. We know little about the genes that underlie the plastic response of traits to the environment, their number, chromosomal locations and genetic interactions as well as environment impact on their effects. Here we review key statistical approaches for analyzing the genetic variation of phenotypic plasticity due to genotype-environment interactions and describe the implementation of a dynamic model to map specific quantitative trait loci (QTLs) that affect the gradient expression of a quantitative trait across a range of environments. This dynamic model is distinct by incorporating mathematical aspects of phenotypic plasticity into a QTL mapping framework, thereby better unraveling the quantitative attribute of trait response to the environment. By testing the curve parameters that specify environment-dependent trajectories of the trait, the model allows a series of fundamental hypotheses to be tested in a quantitative way about the interplay between gene action/interaction and environmental sensitivity. The model can also make the dynamic prediction of genetic control over phenotypic plasticity within the context of changing environments. We demonstrate the usefulness of the model by reanalyzing a QTL data set for rice, gleaning new insights into the genetic basis for phenotypic plasticity in plant height growth. PMID:22396460

Wang, Zhong; Pang, Xiaoming; Lv, Yafei; Xu, Fang; Zhou, Tao; Li, Xin; Feng, Sisi; Li, Jiahan; Li, Zhikang; Wu, Rongling

2012-03-06

309

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

310

Substitution mapping of dth1.1, a flowering-time quantitative trait locus (QTL) associated with transgressive variation in rice, reveals multiple sub-QTL.  

PubMed

A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait. PMID:16452146

Thomson, Michael J; Edwards, Jeremy D; Septiningsih, Endang M; Harrington, Sandra E; McCouch, Susan R

2006-02-01

311

Substitution Mapping of dth1.1, a Flowering-Time Quantitative Trait Locus (QTL) Associated With Transgressive Variation in Rice, Reveals Multiple Sub-QTL  

PubMed Central

A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait.

Thomson, Michael J.; Edwards, Jeremy D.; Septiningsih, Endang M.; Harrington, Sandra E.; McCouch, Susan R.

2006-01-01

312

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

Microsoft Academic Search

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

R. H. Kazmi; N. Khan; L. A. J. Willems; Heusden van A. W; J. W. Ligterink; H. W. M. Hilhorst

2012-01-01

313

Simultaneous three-color analysis of the surface phenotype and DNA-RNA quantitation using 7-amino-actinomycin D and pyronin Y  

Microsoft Academic Search

We developed an improved technique that permits simultaneous DNA and RNA quantitation by a flow cytofluorometry using 7-amino-actinomycin D (7AAD) and pyronin Y (PY), respectively. Detailed cell cycle analyses based upon the cellular DNA\\/RNA levels were performed using cells suspended in a buffer containing 0.004% saponin. This method preserved the light scattering properties of human peripheral blood cells, thus lymphocyte,

Ken Toba; Elliott F. Winton; Tadashi Koike; Akira Shibata

1995-01-01

314

Evolution of salamander life cycles: a major-effect quantitative trait locus contributes to discrete and continuous variation for metamorphic timing.  

PubMed

The evolution of alternate modes of development may occur through genetic changes in metamorphic timing. This hypothesis was examined by crossing salamanders that express alternate developmental modes: metamorphosis vs. paedomorphosis. Three strains were used in the crossing design: Ambystoma tigrinum tigrinum (Att; metamorph), wild-caught A. mexicanum (Am; paedomorph), and laboratory Am (paedomorph). Att/Am hybrids were created for each Am strain and then backcrossed to their respective Am line. Previous studies have shown that a dominant allele from Att (met(Att)) and a recessive allele from lab Am (met(lab)) results in metamorphosis in Att/Am hybrids, and met(Att)/met(lab) and met(lab)/met(lab) backcross genotypes are strongly associated with metamorphosis and paedomorphosis, respectively. We typed a molecular marker (contig325) linked to met and found that met(Att)/met(lab) and met(Att)/met(wild) were associated with metamorphosis in 99% of the cases examined. However, the frequency of paedomorphosis was 4.5 times higher for met(lab)/met(lab) than for met(wild)/met(wild). We also found that met(Att)/met(wild) and met(wild)/met(wild) genotypes discriminated distributions of early and late metamorphosing individuals. Two forms of phenotypic variation are contributed by met: continuous variation of metamorphic age and expression of discrete, alternate morphs. We suggest that the evolution of paedomorphosis is associated with genetic changes that delay metamorphic timing in biphasic life cycles. PMID:15781701

Voss, S R; Smith, J J

2005-03-21

315

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.  

PubMed

More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties. PMID:23471459

Cobb, Joshua N; Declerck, Genevieve; Greenberg, Anthony; Clark, Randy; McCouch, Susan

2013-03-08

316

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  

Microsoft Academic Search

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

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

2008-01-01

317

DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides.  

PubMed

Lipoprotein lipase (LPL) plays a critical role in the metabolism of lipoproteins because this enzyme hydrolyzes the triacylglycerides in chylomicrons and very low density lipoproteins. This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LPL qualifies as a candidate gene for understanding lipid metabolic disorders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivocal results to date. To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism at the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvUII polymorphism, however, showed no association with any lipid. Kruskal-Wallis tests confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertriacylglyceridemia and normolipidemics, a significant difference was observed in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were most at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII polymorphism on both LDL cholesterol and total cholesterol levels. PMID:8026810

Mitchell, R J; Earl, L; Bray, P; Fripp, Y J; Williams, J

1994-06-01

318

Qualitative and quantitative variation among volatile profiles induced by Tetranychus urticae feeding on plants from various families.  

PubMed

Many plant species are known to emit herbivore-induced volatiles in response to herbivory. The spider mite Tetranychus urticae Koch is a generalist that can feed on several hundreds of host plant species. Volatiles emitted by T. urticae-infested plants of 11 species were compared: soybean (Glycine max), golden chain (Laburnum anagyroides), black locust (Robinia pseudo-acacia), cowpea (Vigna unguiculata), tobacco (Nicotiana tabacum), eggplant (Solanum melalonga), thorn apple (Datura stramonium), sweet pepper (Capsicum annuum), hop (Humulus lupulus), grapevine (Vitis vinifera), and ginkgo (Ginkgo biloba). The degree to which the plant species produced novel compounds was analyzed when compared to the odors of mechanically damaged leaves. Almost all of the investigated plant species produced novel compounds that dominated the volatile blend, such as methyl salicylate, terpenes, oximes, and nitriles. Only spider mite-infested eggplant and tobacco emitted a blend that was merely quantitatively different from the blend emitted by mechanically damaged or clean leaves. We hypothesized that plant species with a low degree of direct defense would produce more novel compounds. However, although plant species with a low direct defense level do use indirect defense to defend themselves, they do not always emit novel compounds. Plant species with a high level of direct defense seem to invest in the production of novel compounds. When plant species of the Fabaceae were compared to plant species of the Solanaceae, qualitative differences in spider mite-induced volatile blends seemed to be more prominent in the Fabaceae than in the Solanaceae. PMID:15074658

van den Boom, Cindy E M; van Beek, Teris A; Posthumus, Maarten A; de Groot, Aede; Dicke, Marcel

2004-01-01

319

Variation in heading date conceals quantitative trait loci for other traits of importance in breeding selection of rice  

PubMed Central

To identify quantitative trait loci (QTLs) associated with the primary target traits for selection in practical rice breeding programs, backcross inbred lines (BILs) derived from crosses between temperate japonica rice cultivars Nipponbare and Koshihikari were evaluated for 50 agronomic traits at six experimental fields located throughout Japan. Thirty-three of the 50 traits were significantly correlated with heading date. Using a linkage map including 647 single-nucleotide polymorphisms (SNPs), a total of 122 QTLs for 38 traits were mapped on all rice chromosomes except chromosomes 5 and 9. Fifty-eight of the 122 QTLs were detected near the heading date QTLs Hd16 and Hd17 and the remaining 64 QTLs were found in other chromosome regions. QTL analysis of 51 BILs having homozygous for the Koshihikari chromosome segments around Hd16 and Hd17 allowed us to detect 40 QTLs associated with 27 traits; 23 of these QTLs had not been detected in the original analysis. Among the 97 QTLs for the 30 traits measured in multiple environments, the genotype-by-environment interaction was significant for 44 QTLs and not significant for 53 QTLs. These results led us to propose a new selection strategy to improve agronomic performance in temperate japonica rice cultivars.

Hori, Kiyosumi; Kataoka, Tomomori; Miura, Kiyoyuki; Yamaguchi, Masayuki; Saka, Norikuni; Nakahara, Takahiro; Sunohara, Yoshihiro; Ebana, Kaworu; Yano, Masahiro

2012-01-01

320

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

PubMed

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

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

2013-09-14

321

Genome-Wide Association Analysis with Gray Matter Volume as a Quantitative Phenotype in First-Episode Treatment-Na?ve Patients with Schizophrenia  

PubMed Central

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

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

2013-01-01

322

The Optokinetic Reflex as a Tool for Quantitative Analyses of Nervous System Function in Mice: Application to Genetic and Drug-Induced Variation  

PubMed Central

The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable. We describe a new type of OKR test apparatus in which computer-controlled visual stimuli and streamlined data analysis facilitate a relatively high throughput behavioral assay. We used this apparatus, in conjunction with infrared imaging, to quantify basic OKR stimulus-response characteristics for C57BL/6J and 129/SvEv mouse strains and for genetically engineered lines lacking one or more photoreceptor systems or with an alteration in cone spectral sensitivity. A second generation (F2) cross shows that the characteristic difference in OKR frequency between C57BL/6J and 129/SvEv is inherited as a polygenic trait. Finally, we demonstrate the sensitivity and high temporal resolution of the OKR for quantitative analysis of CNS drug action. These experiments show that the mouse OKR is well suited for neurologic testing in the context of drug discovery and large-scale phenotyping programs.

Cahill, Hugh; Nathans, Jeremy

2008-01-01

323

QTL and quantitative genetic analysis of beak morphology reveals patterns of standing genetic variation in an Estrildid finch.  

PubMed

The intra- and interspecific diversity of avian beak morphologies is one of the most compelling examples for the power of natural selection acting on a morphological trait. The development and diversification of the beak have also become a textbook example for evolutionary developmental biology, and variation in expression levels of several genes is known to causally affect beak shape. However, until now, no genomic polymorphisms have been identified, which are related to beak morphology in birds. QTL mapping does reveal the location of causal polymorphisms, albeit with poor spatial resolution. Here, we estimate heritability and genetic correlations for beak length, depth and width and perform a QTL linkage analysis for these traits based on 1404 informative single-nucleotide polymorphisms genotyped in a four-generation pedigree of 992 captive zebra finches (Taeniopygia guttata). Beak size, relative to body size, was sexually dimorphic (larger in males). Heritability estimates ranged from 0.47 for beak length to 0.74 for beak width. QTL mapping revealed four to five regions of significant or suggestive genome-wide linkage for each of the three beak dimensions (nine different regions in total). Eight out of 11 genes known to influence beak morphology are located in these nine peak regions. Five QTL do not cover known candidates demonstrating that yet unknown genes or regulatory elements may influence beak morphology in the zebra finch. PMID:22694741

Knief, Ulrich; Schielzeth, Holger; Kempenaers, Bart; Ellegren, Hans; Forstmeier, Wolfgang

2012-06-13

324

Quantitative and qualitative variation of fat in model vanilla custard desserts: effects on sensory properties and consumer acceptance.  

PubMed

The effects of variation in fat content (0.1% to 15.8%) and type of fat, using different types of milk, dairy cream, or vegetable fat cream, on sensory characteristics and consumer acceptance of starch-based vanilla model custards were studied. Descriptive analysis with trained panelists and consumer testing with untrained assessors were applied. Descriptive data were related to hedonic data using principal component analysis to determine drivers of liking and disliking. Results demonstrated an increasing effect of fat concerning visual and oral thickness, creamy flavor, and fat-related texture properties, as well as a decreasing effect concerning yellow color and surface shine. A lack of fat caused moderate intensities in pudding-like flavor attributes and an intensive jelly texture. Adding a vegetable fat cream led to lower intensities in attributes yellow color, cooked flavor, thick, and jelly texture, whereas intensities in vegetable fat flavor and fat-related texture properties increased. All consumers favored custards with medium fat contents, being high in pudding-like and vegetable fat flavor as well as in fat-related texture attributes. Nonfat custards were rejected due to jelly texture and moderate intensities in pudding-flavor attributes. High-fat samples were liked by some consumers, but their high intensities in thickness, white color, and creamy flavor also drove disliking for others. PMID:23772708

Tomaschunas, Maja; Köhn, Ehrhard; Bennwitz, Petra; Hinrichs, Jörg; Busch-Stockfisch, Mechthild

2013-06-01

325

Genome-wide Association Study of N370S Homozygous Gaucher Disease Reveals the Candidacy of CLN8 gene as a Genetic Modifier Contributing to Extreme Phenotypic Variation  

PubMed Central

Mutations in GBA1 gene result in defective acid ?-glucosidase and the complex phenotype of Gaucher disease (GD) related to the accumulation of glucosylceramide-laden macrophages. The phenotype is highly variable even among patients harboring identical GBA1 mutations. We hypothesized that modifier gene(s) underlie phenotypic diversity in GD and performed a GWAS study in Ashkenazi Jewish patients with type 1 GD (GD1), homozygous for N370S mutation. Patients were assigned to mild, moderate or severe disease category using composite disease severity scoring systems. Whole-genome genotyping for >500,000 SNPs was performed to search for associations using OQLS algorithm in 139 eligible patients. Several SNPs in linkage disequilibrium within the CLN8 gene locus were associated with the GD1 severity: SNP rs11986414 was associated with GD1 severity at p value 1.26 × 10?6. Compared to mild disease, risk allele A at rs11986414 conferred an odds ratio of 3.72 for moderate/severe disease. Loss of function mutations in CLN8 causes neuronal ceroid-lipofuscinosis but our results indicate that its increased expression may protect against severe GD1. In cultured skin fibroblasts, the relative expression of CLN8 was higher in mild GD compared to severely affected patients in whom CLN8 risk alleles were over-represented. In an in vitro cell model of GD, CLN8 expression was increased which was further enhanced in the presence of bioactive substrate, glucosylsphingosine. Taken together, CLN8 is a candidate modifier gene for GD1 that may function as a protective sphingolipid sensor and/or in glycosphingolipid trafficking. Future studies should explore the role of CLN8 in pathophysiology of GD.

Zhang, Clarence K.; Stein, Philip B.; Liu, Jun; Pastores, Gregory M.; Wang, Zuoheng; Yang, Ruhua; Cho, Judy H.; Gregersen, Peter K.; Aerts, Johannes M. F. G.; Zhao, Hongyu; Mistry, Pramod K.

2013-01-01

326

Genome-wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation.  

PubMed

Mutations in GBA1 gene result in defective acid ?-glucosidase and the complex phenotype of Gaucher disease (GD) related to the accumulation of glucosylceramide-laden macrophages. The phenotype is highly variable even among patients harboring identical GBA1 mutations. We hypothesize that modifier gene(s) underlie phenotypic diversity in GD and performed a GWAS study in Ashkenazi Jewish patients with type 1 GD (GD1), homozygous for N370S mutation. Patients were assigned to mild, moderate, or severe disease categories using composite disease severity scoring systems. Whole-genome genotyping for >500,000 SNPs was performed to search for association signals using OQLS algorithm in 139 eligible patients. Several SNPs in linkage disequilibrium within the CLN8 gene locus were associated with the GD1 severity: SNP rs11986414 was associated with GD1 severity at P value 1.26 × 10(-6) . Compared to mild disease, risk allele A at rs11986414 conferred an odds ratio of 3.72 for moderate/severe disease. Loss of function mutations in CLN8 causes neuronal ceroid-lipofuscinosis, but our results indicate that its increased expression may protect against severe GD1. In cultured skin fibroblasts, the relative expression of CLN8 was higher in mild GD compared to severely affected patients, in whom CLN8 risk alleles were overrepresented. In an in vitro cell model of GD, CLN8 expression was increased, which was further enhanced in the presence of bioactive substrate, glucosylsphingosine. Taken together, CLN8 is a candidate modifier gene for GD1 that may function as a protective sphingolipid sensor and/or in glycosphingolipid trafficking. Future studies should explore the role of CLN8 in pathophysiology of GD. PMID:22388998

Zhang, Clarence K; Stein, Philip B; Liu, Jun; Wang, Zuoheng; Yang, Ruhua; Cho, Judy H; Gregersen, Peter K; Aerts, Johannes M F G; Zhao, Hongyu; Pastores, Gregory M; Mistry, Pramod K

2012-03-03

327

Phylogenetic classification at generic level in the absence of distinct phylogenetic patterns of phenotypical variation: a case study in graphidaceae (ascomycota).  

PubMed

Molecular phylogenies often reveal that taxa circumscribed by phenotypical characters are not monophyletic. While re-examination of phenotypical characters often identifies the presence of characters characterizing clades, there is a growing number of studies that fail to identify diagnostic characters, especially in organismal groups lacking complex morphologies. Taxonomists then can either merge the groups or split taxa into smaller entities. Due to the nature of binomial nomenclature, this decision is of special importance at the generic level. Here we propose a new approach to choose among classification alternatives using a combination of morphology-based phylogenetic binning and a multiresponse permutation procedure to test for morphological differences among clades. We illustrate the use of this method in the tribe Thelotremateae focusing on the genus Chapsa, a group of lichenized fungi in which our phylogenetic estimate is in conflict with traditional classification and the morphological and chemical characters do not show a clear phylogenetic pattern. We generated 75 new DNA sequences of mitochondrial SSU rDNA, nuclear LSU rDNA and the protein-coding RPB2. This data set was used to infer phylogenetic estimates using maximum likelihood and Bayesian approaches. The genus Chapsa was found to be polyphyletic, forming four well-supported clades, three of which clustering into one unsupported clade, and the other, supported clade forming two supported subclades. While these clades cannot be readily separated morphologically, the combined binning/multiresponse permutation procedure showed that accepting the four clades as different genera each reflects the phenotypical pattern significantly better than accepting two genera (or five genera if splitting the first clade). Another species within the Thelotremateae, Thelotrema petractoides, a unique taxon with carbonized excipulum resembling Schizotrema, was shown to fall outside Thelotrema. Consequently, the new genera Astrochapsa, Crutarndina, Pseudochapsa, and Pseudotopeliopsis are described here and 39 new combinations are proposed. PMID:23251515

Parnmen, Sittiporn; Lücking, Robert; Lumbsch, H Thorsten

2012-12-12

328

Bending Amplitude-- a New Quantitative Assay of C. elegans Locomotion: Identification of Phenotypes for Mutants in Genes Encoding Muscle Focal Adhesion Components  

PubMed Central

The nematode Caenorhabditis elegans uses striated muscle in its body wall for locomotion. The myofilament lattice is organized such that all the thin filament attachment structures (dense bodies, analogous to Z-disks) and thick filament organizing centers (M-lines) are attached to the muscle cell membrane. Thus, the force of muscle contraction is transmitted through these structures and allows locomotion of the worm. Dense bodies and M-lines are compositionally similar to focal adhesions and costameres, and are based on integrin and associated proteins. Null mutants for many of the newly discovered dense body and M-line proteins do not have obvious locomotion defects when observed casually, or when assayed by counting the number of times a worm moves back and forth in liquid. We hypothesized that many of these proteins, located as they are in muscle focal adhesions, function in force transmission, but we had not used an appropriate or sufficiently sensitive assay to reveal this function. Recently, we have developed a new quantitative assay of C. elegans locomotion that measures the maximum bending amplitude of an adult worm as it moves backwards. The assay had been used to reveal locomotion defects for null mutants of genes encoding ATN-1 (?-actinin) and PKN-1 (protein kinase N). Here, we describe the details of this method, and apply it to 21 loss of function mutants in 17 additional genes, most of which encode components of muscle attachment structures. As compared to wild type, mutations in 11 genes were found to have less ability to bend, and mutations in one gene were found to have greater ability to bend. Loss of function mutants for eight proteins had been reported to have normal locomotion (ZYX-1(zyxin), ALP-1 (Enigma), DIM-1, SCPL-1), or locomotion that was not previously investigated (FRG-1 (FRG1), KIN-32 (focal adhesion kinase, LIM-8), or had only slightly decreased locomotion (PFN-3 (profilin)).

Nahabedian, John F.; Qadota, Hiroshi; Stirman, Jeffrey N.; Lu, Hang; Benian, Guy M.

2011-01-01

329

A real-time semi-quantitative RT-PCR assay demonstrates that the pilE sequence dictates the frequency and characteristics of pilin antigenic variation in Neisseria gonorrhoeae  

Microsoft Academic Search

A semi-quantitative real-time RT-PCR assay was designed to measure gonococcal pilin antigenic- variation (SQ-PCR Av assay). This assay employs 17 hybridization probe sets that quantitate sub- populations of pilin transcripts carrying different silent pilin copy sequences and one set that detects total pilE transcript levels. Mixtures of a DNA stan- dard carrying the silent copy being detected and a clone

Melissa S. Rohrer; Matthew P. Lazio; H. Steven Seifert

2005-01-01

330

High-dimensional and large-scale phenotyping of yeast mutants  

PubMed Central

One of the most powerful techniques for attributing functions to genes in uni- and multicellular organisms is comprehensive analysis of mutant traits. In this study, systematic and quantitative analyses of mutant traits are achieved in the budding yeast Saccharomyces cerevisiae by investigating morphological phenotypes. Analysis of fluorescent microscopic images of triple-stained cells makes it possible to treat morphological variations as quantitative traits. Deletion of nearly half of the yeast genes not essential for growth affects these morphological traits. Similar morphological phenotypes are caused by deletions of functionally related genes, enabling a functional assignment of a locus to a specific cellular pathway. The high-dimensional phenotypic analysis of defined yeast mutant strains provides another step toward attributing gene function to all of the genes in the yeast genome.

Ohya, Yoshikazu; Sese, Jun; Yukawa, Masashi; Sano, Fumi; Nakatani, Yoichiro; Saito, Taro L.; Saka, Ayaka; Fukuda, Tomoyuki; Ishihara, Satoru; Oka, Satomi; Suzuki, Genjiro; Watanabe, Machika; Hirata, Aiko; Ohtani, Miwaka; Sawai, Hiroshi; Fraysse, Nicolas; Latge, Jean-Paul; Francois, Jean M.; Aebi, Markus; Tanaka, Seiji; Muramatsu, Sachiko; Araki, Hiroyuki; Sonoike, Kintake; Nogami, Satoru; Morishita, Shinichi

2005-01-01

331

Genetic variation, heritability, divergence and biomass accumulation of rice genotypes resistant to bacterial blight revealed by quantitative traits and ISSR markers.  

PubMed

A field experiment was carried out in order to evaluate genetic diversity of 41 rice genotypes using physiological traits and molecular markers. All the genotypes unveiled variations for crop growth rate (CGR), relative growth rate (RGR), net assimilation rate (NAR), yield per hill (Yhill(-1) ), total dry matter (TDM), harvest index (HI), photosynthetic rate (PR), leaf area index (LAI), chlorophyll-a and chlorophyll-b at maximum tillering stage. The CGR values varied from 0.23 to 0.76 gm cm(-2) ?day(-1) . The Yhill(-1) ranged from 15.91 to 92.26?g, while TDM value was in the range of 7.49 to 20.45?g hill(-1) . PR was found to vary from 9.40 to 22.34 µmol m(-2) s(-1) . PR expressed positive relation with Yhill(-1) . Significant positive relation was found between CGR and TDM (r?=?0.61**), NAR and CGR (r?=?0.62**) and between TDM and NAR (r?=?0.31**). High heritability was found in RGR and Yhill(-1) . Cluster analysis based on the traits grouped 41 rice genotypes into seven clusters. A total of 310 polymorphic loci were detected across the 20 inter-simple sequence repeats (ISSR) markers. The UPGMA dendrogram grouped 41 rice genotypes into 11 clusters including several sub-clusters. The Mantel test revealed positive correlation between quantitative traits and molecular markers (r?=?0.41). On the basis of quantitative traits and molecular marker analyses parental genotypes, IRBB54 with MR84, IRBB60 with MR84, Purbachi with MR263, IRBB65 with BR29, IRBB65 with Pulut Siding and MRQ74 with Purbachi could be hybridized for future breeding program. PMID:23521023

Mazid, Muhammad S; Rafii, Mohd Y; Hanafi, Mohamed M; Rahim, Harun A; Latif, Md Abdul

2013-04-16

332

Genome wide search for variation associated with micronutrient density of developing rice grains  

Technology Transfer Automated Retrieval System (TEKTRAN)

"Omic" tools are rapidly being employed to delineate the biological framework controlling phenotypes of interest in crop species. An advanced understanding of the genetic basis for quantitative trait variation has been made possible through genome wide association studies (GWAS) that make use of gen...

333

Genome wide search for variation associated with micronutrient density of developing rice grains  

Technology Transfer Automated Retrieval System (TEKTRAN)

“Omic” tools are rapidly being employed to delineate the biological framework controlling phenotypes of interest in crop species. An advanced understanding of the genetic basis for quantitative trait variation has been made possible through genome wide association studies (GWAS) that make use of ge...

334

Genome Partitioning of Genetic Variation for Height from 11,214 Sibling Pairs  

Microsoft Academic Search

Height has been used for more than a century as a model by which to understand quantitative genetic variation in humans. We report that the entire genome appears to contribute to its additive genetic variance. We used genotypes and phenotypes of 11,214 sibling pairs from three countries to partition additive genetic variance across the genome. Using genome scans to estimate

Peter M. Visscher; Stuart Macgregor; Beben Benyamin; Gu Zhu; Scott Gordon; Sarah Medland; William G. Hill; Jouke-Jan Hottenga; Gonneke Willemsen; Dorret I. Boomsma; Yao-Zhong Liu; Hong-Wen Deng; Grant W. Montgomery; Nicholas G. Martin

2007-01-01

335

Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population  

Microsoft Academic Search

The melanocortin-1 receptor (MC1R) and P gene product are two important components of the human pigmentary system that have been shown to be associated with red hair\\/fair skin and cause type II oculocutaneous albinism, respectively. However, their contribution to inter-individual variation at the population level is not well defined. To this end, we genotyped 3 single nucleotide polymorphisms (SNPs) in

Joshua M. Akey; Hong Wang; Momiao Xiong; Hong Wu; Weida Liu; Mark D. Shriver; Li Jin

2001-01-01

336

Neisseria meningitidis Escape from the Bactericidal Activity of a Monoclonal Antibody Is Mediated by Phase Variation of lgtG and Enhanced by a Mutator Phenotype  

Microsoft Academic Search

Bacteria adapt to environmental changes through high-frequency switches in expression of specific pheno- types. Localized hypermutation mediated by simple sequence repeats is an important mechanism of such phase variation (PV) in Neisseria meningitidis. Loss or gain of nucleotides in a poly(C) tract located in the reading frame results in switches in expression of lgtG and determines whether a glucose or

Christopher D. Bayliss; J. Claire Hoe; Katherine Makepeace; Patricia Martin; Derek W. Hood; E. Richard Moxon

2008-01-01

337

Spatial and temporal variation in the kdr allele L1014S in Anopheles gambiae s.s. and phenotypic variability in susceptibility to insecticides in Western Kenya  

Microsoft Academic Search

BACKGROUND: Malaria vector control in Africa depends upon effective insecticides in bed nets and indoor residual sprays. This study investigated the extent of insecticide resistance in Anopheles gambiae s.l., Anopheles gambiae s.s. and Anopheles arabiensis in western Kenya where ownership of insecticide-treated bed nets has risen steadily from the late 1990s to 2010. Temporal and spatial variation in the frequency

Derrick K Mathias; Eric Ochomo; Francis Atieli; Maurice Ombok; M Nabie Bayoh; George Olang; Damaris Muhia; Luna Kamau; John M Vulule; Mary J Hamel; William A Hawley; Edward D Walker; John E Gimnig

2011-01-01

338

Genetic variation in major phenotypic traits among diverse genetic origins of teak ( Tectona grandis L.f.) planted in Taliwas, Sabah, East Malaysia  

Microsoft Academic Search

• Introduction\\u000a   As a forest species, genetic variability is high in teak (Tectona grandis) and domestication of the species is very recent. The selection effect among qualitative and quantitative traits is therefore\\u000a expected to be strong. Native provenances and clonal seed orchard families were compared in this study.\\u000a \\u000a \\u000a \\u000a \\u000a • Materials and methods\\u000a   Forty-one genetic origins of teak, including 26 open-pollinated

Gilles Chaix; Olivier Monteuuis; Charles Garcia; David Alloysius; Jikos Gidiman; Roberto Bacilieri; Doreen K. S. Goh

339

Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations  

PubMed Central

Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world.

Candille, Sophie I.; Absher, Devin M.; Beleza, Sandra; Bauchet, Marc; McEvoy, Brian; Garrison, Nanibaa' A.; Li, Jun Z.; Myers, Richard M.; Barsh, Gregory S.; Tang, Hua; Shriver, Mark D.

2012-01-01

340

Quantitative variation in water-use efficiency across water regimes and its relationship with circadian, vegetative, reproductive, and leaf gas-exchange traits.  

PubMed

Drought limits light harvesting, resulting in lower plant growth and reproduction. One trait important for plant drought response is water-use efficiency (WUE). We investigated (1) how the joint genetic architecture of WUE, reproductive characters, and vegetative traits changed across drought and well-watered conditions, (2) whether traits with distinct developmental bases (e.g. leaf gas exchange versus reproduction) differed in the environmental sensitivity of their genetic architecture, and (3) whether quantitative variation in circadian period was related to drought response in Brassica rapa. Overall, WUE increased in drought, primarily because stomatal conductance, and thus water loss, declined more than carbon fixation. Genotypes with the highest WUE in drought expressed the lowest WUE in well-watered conditions, and had the largest vegetative and floral organs in both treatments. Thus, large changes in WUE enabled some genotypes to approach vegetative and reproductive trait optima across environments. The genetic architecture differed for gas-exchange and vegetative traits across drought and well-watered conditions, but not for floral traits. Correlations between circadian and leaf gas-exchange traits were significant but did not vary across treatments, indicating that circadian period affects physiological function regardless of water availability. These results suggest that WUE is important for drought tolerance in Brassica rapa and that artificial selection for increased WUE in drought will not result in maladaptive expression of other traits that are correlated with WUE. PMID:22319207

Edwards, Christine E; Ewers, Brent E; McClung, C Robertson; Lou, Ping; Weinig, Cynthia

2012-02-08

341

Correlation Assessment among Clinical Phenotypes, Expression Analysis and Molecular Modeling of 14 Novel Variations in the Human Galactose-1-phosphate Uridylyltransferase Gene  

PubMed Central

Galactose-1-phosphate uridylyltransferase (GALT) catalyses the conversion of galactose-1-phosphate to UDP-galactose, a key step in the galactose metabolism. Deficiency of GALT activity in humans caused by deleterious variations in the GALT gene can cause a potentially lethal disease called Classic Galactosemia. In this study, we selected 14 novel nucleotide sequence changes in the GALT genes found in galactosemic patients for expression analysis and molecular modeling. Several variants showed decreased levels of expression and decreased abundance in the soluble fraction of the Escherichia coli cell extracts, suggesting altered stability and solubility. Only six variant GALT enzymes had detectable enzymatic activities. Kinetic studies showed that their Vmax decreased significantly. To further characterize the variants at molecular level, we performed static and dynamic molecular modeling studies. Effects of variations on local and/or global structural features of the enzyme were anticipated for the majority of variants. In-depth studies with molecular dynamic simulations on selected variants predicted the alteration of the protein structure even when static models apparently did not highlight any perturbation. Overall, these studies offered new insights on the molecular properties of GALT enzyme, with the aim of correlating them with the clinical outcome.

Tang, Manshu; Facchiano, Angelo; Rachamadugu, Rakesh; Calderon, Fernanda; Mao, Rong; Milanesi, Luciano; Marabotti, Anna; Lai, Kent

2012-01-01

342

Asthma phenotypes  

Microsoft Academic Search

The many roads leading to the syndrome of asthma have proven to be intricately interconnected. The chronic inflammation of\\u000a asthma is characterized by airway hyperreactivity and variable reversibility. Past classification systems relied on assessment\\u000a of daily impairment and the distinction between intrinsic (nonallergic) and extrinsic (allergic). With more precise asthma\\u000a phenotypes, association studies likely will have greater significance. In addition,

Steve Handoyo; Lanny J. Rosenwasser

2009-01-01

343

`Weak A' phenotypes  

PubMed Central

Thirty-five weak A samples including fourteen A3, eight Ax, seven Aend, three Am and three Ae1 were studied in order to determine their A antigen site density, using an IgG anti-A labelled with 125I. The values obtained ranged between 30,000 A antigen sites for A3 individuals, and 700 sites for the Ae1 red cells. The hierarchy of values observed made it possible to establish a quantitative relationship between the red cell agglutinability of these phenotypes measured under standard conditions, and their antigen site density.

Cartron, J. P.; Gerbal, A.; Hughes-Jones, N. C.; Salmon, C.

1974-01-01

344

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

PubMed

Amylose extender (ae(-)) starches characteristically have modified starch granule morphology resulting from amylopectin with reduced branch frequency and longer glucan chains in clusters, caused by the loss of activity of the major starch branching enzyme (SBE), which in maize endosperm is SBEIIb. A recent study with ae(-) maize lacking the SBEIIb protein (termed ae1.1 herein) showed that novel protein-protein interactions between enzymes of starch biosynthesis in the amyloplast could explain the starch phenotype of the ae1.1 mutant. The present study examined an allelic variant of the ae(-) mutation, ae1.2, which expresses a catalytically inactive form of SBEIIb. The catalytically inactive SBEIIb in ae1.2 lacks a 28 amino acid peptide (Val272-Pro299) and is unable to bind to amylopectin. Analysis of starch from ae1.2 revealed altered granule morphology and physicochemical characteristics distinct from those of the ae1.1 mutant as well as the wild-type, including altered apparent amylose content and gelatinization properties. Starch from ae1.2 had fewer intermediate length glucan chains (degree of polymerization 16-20) than ae1.1. Biochemical analysis of ae1.2 showed that there were differences in the organization and assembly of protein complexes of starch biosynthetic enzymes in comparison with ae1.1 (and wild-type) amyloplasts, which were also reflected in the composition of starch granule-bound proteins. The formation of stromal protein complexes in the wild-type and ae1.2 was strongly enhanced by ATP, and broken by phosphatase treatment, indicating a role for protein phosphorylation in their assembly. Labelling experiments with [?-(32)P]ATP showed that the inactive form of SBEIIb in ae1.2 was phosphorylated, both in the monomeric form and in association with starch synthase isoforms. Although the inactive SBEIIb was unable to bind starch directly, it was strongly associated with the starch granule, reinforcing the conclusion that its presence in the granules is a result of physical association with other enzymes of starch synthesis. In addition, an Mn(2+)-based affinity ligand, specific for phosphoproteins, was used to show that the granule-bound forms of SBEIIb in the wild-type and ae1.2 were phosphorylated, as was the granule-bound form of SBEI found in ae1.2 starch. The data strongly support the hypothesis that the complement of heteromeric complexes of proteins involved in amylopectin synthesis contributes to the fine structure and architecture of the starch granule. PMID:22121198

Liu, Fushan; Ahmed, Zaheer; Lee, Elizabeth A; Donner, Elizabeth; Liu, Qiang; Ahmed, Regina; Morell, Matthew K; Emes, Michael J; Tetlow, Ian J

2011-11-25

345

Phenotypic variation resulting from a deficiency of epidermal growth factor receptor in mice is caused by extensive genetic heterogeneity that can be genetically and molecularly partitioned.  

PubMed Central

The timing of lethality caused by homozygosity for a null allele of the epidermal growth factor receptor (Egfrtm1Mag) in mice is strongly dependent on genetic background. Initial attempts to genetically map background modifiers using Swiss-derived, outbred CD-1 mice were unsuccessful. To investigate the genetic architecture contributing to survival of Egfrtm1Mag homozygous embryos, the genetic variability segregating within the outbred population was partitioned by surveying viability of Egfrtm1Mag mutants using intercrosses between 129S6/SvEvTAC-Egfrtm1Mag and nine Swiss-derived, inbred strains: ALR/LtJ, ALS/LtJ, APN, APS, ICR/HaRos, NOD/LtJ, NON/LtJ, SJL/J, and SWR/J. The observations showed that these strains support varying levels of survival of Egfrtm1Mag homozygous embryos, suggesting that genetic heterogeneity within the CD-1 stock contributed to the original lack of Egfrtm1Mag modifier detection. Similar to the Swiss-derived intercrosses, nine congenic strains, derived from 129S6/SvEvTAC, AKR/J, APN, BALB/cJ, BTBR-T+ tf/tf, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ inbred backgrounds, also supported varying levels of survival of Egfrtm1Mag mutants. By intercrossing the congenic lines to create hybrid F1 embryos, different genetic backgrounds were found to have complementary modifiers. Analysis of the congenic lines argues against heterosis of outbred backgrounds contributing to Egfrtm1Mag phenotypic variability. A detailed analysis of the crosses suggests that modifiers function at three distinct stages of development. One class of modifiers supports survival of Egfrtm1Mag homozygous embryos to mid-gestation, another class supports development through the mid-gestation transition from yolk-sac to placental-derived nutrient sources, and a third class supports survival through later stages of gestation. Data from microarray analysis using RNA from wild-type and Egfrtm1Mag mutant placentas support the existence of extensive genetic heterogeneity and suggest that it can be molecularly partitioned. This method should be generally useful to partition heterogeneity contributing to other complex traits.

Strunk, Karen E; Amann, Vicky; Threadgill, David W

2004-01-01

346

Male fertility versus sterility, cytotype, and DNA quantitative variation in seed production in diploid and tetraploid sea lavenders (Limonium sp., Plumbaginaceae) reveal diversity in reproduction modes.  

PubMed

The genus Limonium Miller, a complex taxonomic group, comprises annuals and perennials that can produce sexual and/or asexual seeds (apomixis). In this study, we used diverse cytogenetic and cytometric approaches to analyze male sporogenesis and gametogenesis for characterizing male reproductive output on seed production in Limonium ovalifolium and Limonium multiflorum. We showed here that the first species is mostly composed of diploid cytotypes with 2n = 16 chromosomes and the latter species by tetraploid cytotypes with 2n = 32, 34, 35, 36 chromosomes and had a genome roughly twice as big as the former one. In both species, euploid and aneuploid cytotypes with large metacentric chromosomes having decondensed interstitial sites were found within and among populations, possibly involved in chromosomal reconstructions. L. ovalifolium diploids showed regular meiosis resulting in normal tetrads, while diverse chromosome pairing and segregation irregularities leading to the formation of abnormal meiotic products are found in balanced and non-balanced L. multiflorum tetraploids. Before anther dehiscence, the characteristic unicellular, bicellular, or tricellular pollen grains showing the typical Limonium micro- or macro-reticulate exine ornamentation patterns were observed in L. ovalifolium using scanning electron microscopy. Most of these grains were viable and able to produce pollen tubes in vitro. In both balanced and unbalanced L. multiflorum tetraploids, microspores only developed until the "ring-vacuolate stage" with a collapsed morphology without the typical exine patterns, pointing to a sporophytic defect. These microspores were unviable and therefore never germinated in vitro. L. ovalifolium individuals presented larger pollen grains than those of L. multiflorum, indicating that pollen size and ploidy levels are not correlated in the Limonium system. Cytohistological studies in mature seeds from both species revealed that an embryo and a residual endosperm were present in each seed. Flow cytometric seed screens using such mature seeds showed quantitative variations in seeds ploidy level. It is concluded that male function seems to play an important role in the reproduction modes of Limonium diploids and tetraploids. PMID:23086613

Róis, Ana Sofia; Teixeira, Generosa; Sharbel, Timothy F; Fuchs, Jörg; Martins, Sérgio; Espírito-Santo, Dalila; Caperta, Ana D

2012-10-20

347

Quantitative PCR reveals strong spatial and temporal variation of the wasting disease pathogen, Labyrinthula zosterae in northern European eelgrass (Zostera marina) beds.  

PubMed

Seagrass beds are the foundation species of functionally important coastal ecosystems worldwide. The world's largest losses of the widespread seagrass Zostera marina (eelgrass) have been reported as a consequence of wasting disease, an infection with the endophytic protist Labyrinthula zosterae. During one of the most extended epidemics in the marine realm, ?90% of East and Western Atlantic eelgrass beds died-off between 1932 and 1934. Today, small outbreaks continue to be reported, but the current extent of L. zosterae in European meadows is completely unknown. In this study we quantify the abundance and prevalence of the wasting disease pathogen among 19 Z. marina populations in northern European coastal waters, using quantitative PCR (QPCR) with primers targeting a species specific portion of the internally transcribed spacer (ITS1) of L. zosterae. Spatially, we found marked variation among sites with abundances varying between 0 and 126 cells mg(-1) Z. marina dry weight (mean: 5.7 L. zosterae cells mg(-1) Z. marina dry weight ±1.9 SE) and prevalences ranged from 0-88.9%. Temporarily, abundances varied between 0 and 271 cells mg(-1) Z. marina dry weight (mean: 8.5±2.6 SE), while prevalences ranged from zero in winter and early spring to 96% in summer. Field concentrations accessed via bulk DNA extraction and subsequent QPCR correlated well with prevalence data estimated via isolation and cultivation from live plant tissue. L. zosterae was not only detectable in black lesions, a sign of Labyrinthula-induced necrosis, but also occurred in green, apparently healthy tissue. We conclude that L. zosterae infection is common (84% infected populations) in (northern) European eelgrass populations with highest abundances during the summer months. In the light of global climate change and increasing rate of marine diseases our data provide a baseline for further studies on the causes of pathogenic outbreaks of L. zosterae. PMID:23658711

Bockelmann, Anna-Christina; Tams, Verena; Ploog, Jana; Schubert, Philipp R; Reusch, Thorsten B H

2013-05-02

348

Advancing Genetic Theory and Application by Metabolic Quantitative Trait Loci Analysis  

PubMed Central

This review describes recent advances in the analysis of metabolism using quantitative genetics. It focuses on how recent metabolic quantitative trait loci (QTL) studies enhance our understanding of the genetic architecture underlying naturally variable phenotypes and the impact of this fundamental research on agriculture, specifically crop breeding. In particular, the role of whole-genome duplications in generating quantitative genetic variation within a species is highlighted and the potential uses of this phenomenon presented. Additionally, the review describes how new observations from metabolic QTL mapping analyses are helping to shape and expand the concepts of genetic epistasis.

Kliebenstein, DanielJ.

2009-01-01

349

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

PubMed Central

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

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

2002-01-01

350

Evidence that Egfr Contributes to Cryptic Genetic Variation for Photoreceptor Determination in Natural Populations of Drosophila melanogaster  

Microsoft Academic Search

One objective of quantitative genetics is to identify the nucleotide variants within genes that contribute to phenotypic variation and susceptibility [1]. In an evolutionary context, this means characterizing the molecular polymorphisms that modify the penetrance and expressivity of perturbed traits. A survey of association between 267 SNPs in almost 11 kb of the D. melanogaster Egfr and the degree of

Ian Dworkin; Arnar Palsson; Kelli Birdsall; Greg Gibson

2003-01-01

351

Three monthly coral Sr\\/Ca records from the Chagos Archipelago covering the period of 1950–1995 A.D.: reproducibility and implications for quantitative reconstructions of sea surface temperature variations  

Microsoft Academic Search

In order to assess the fidelity of coral Sr\\/Ca for quantitative reconstructions of sea surface temperature variations, we\\u000a have generated three monthly Sr\\/Ca time series from Porites corals from the lagoon of Peros Banhos (71°E, 5°S, Chagos Archipelago). We find that all three coral Sr\\/Ca time series are\\u000a well correlated with instrumental records of sea surface temperature (SST) and air

Miriam Pfeiffer; Wolf-Christian Dullo; Jens Zinke; Dieter Garbe-Schönberg

2009-01-01

352

Combining Genome-Wide Methods to Investigate the Genetic Complexity of Courtship Song Variation in Drosophila melanogaster.  

PubMed

Little is currently known about the genetic complexity of quantitative behavioral variation, the types of genes involved, or their effects on intermediate phenotypes. Here, we conduct a genome-wide association study of Drosophila melanogaster courtship song variation using 168 sequenced inbred lines, and fail to find highly significant associations. However, by combining these data with results from a well-powered Evolve and Resequence (E&R) study on the same trait, we provide statistical evidence that some power to associate genotype and phenotype is available. Genes that are significant in both analyses are enriched for expression in the nervous system, and affect neural development and synaptic growth when perturbed. Quantitative complementation at one of these loci, Syntrophin-like 1, supports a hypothesis that variation at this locus affects variation in the inter-pulse interval of courtship song. These results suggest that experimental evolution may provide an approach for genome-scale replication in Drosophila. PMID:23777628

Turner, Thomas L; Miller, Paige M; Cochrane, Veronica A

2013-06-18

353

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

PubMed

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

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

2008-09-18

354

phenosim - A software to simulate phenotypes for testing in genome-wide association studies  

PubMed Central

Background There is a great interest in understanding the genetic architecture of complex traits in natural populations. Genome-wide association studies (GWAS) are becoming routine in human, animal and plant genetics to understand the connection between naturally occurring genotypic and phenotypic variation. Coalescent simulations are commonly used in population genetics to simulate genotypes under different parameters and demographic models. Results Here, we present phenosim, a software to add a phenotype to genotypes generated in time-efficient coalescent simulations. Both qualitative and quantitative phenotypes can be generated and it is possible to partition phenotypic variation between additive effects and epistatic interactions between causal variants. The output formats of phenosim are directly usable as input for different GWAS tools. The applicability of phenosim is shown by simulating a genome-wide association study in Arabidopsis thaliana. Conclusions By using the coalescent approach to generate genotypes and phenosim to add phenotypes, the data sets can be used to assess the influence of various factors such as demography, genetic architecture or selection on the statistical power of association methods to detect causal genetic variants under a wide variety of population genetic scenarios. phenosim is freely available from the authors' website http://evoplant.uni-hohenheim.de

2011-01-01

355

A collective mechanism for phase variation in biofilms  

NASA Astrophysics Data System (ADS)

Understanding how microbes gather into biofilm communities and maintain diversity remains one of the central questions of microbiology, requiring an understanding of microbes as communal rather then individual organisms. Phase variation plays an integral role in the formation of diverse phenotypes within biofilms. We propose a collective mechanism for phase variation based on gene transfer agents, and apply the theory to predict the population structure and growth dynamics of a biofilm. Our results describe quantitatively recent experiments, with the only adjustable parameter being the rate of intercellular horizontal gene transfer. Our approach derives from a more general picture for the emergence of cooperation between microbes.

Chia, Nicholas; Woese, Carl; Goldenfeld, Nigel

2009-03-01

356

Quantitative imaging in cancer evolution and ecology.  

PubMed

Cancer therapy, even when highly targeted, typically fails because of the remarkable capacity of malignant cells to evolve effective adaptations. These evolutionary dynamics are both a cause and a consequence of cancer system heterogeneity at many scales, ranging from genetic properties of individual cells to large-scale imaging features. Tumors of the same organ and cell type can have remarkably diverse appearances in different patients. Furthermore, even within a single tumor, marked variations in imaging features, such as necrosis or contrast enhancement, are common. Similar spatial variations recently have been reported in genetic profiles. Radiologic heterogeneity within tumors is usually governed by variations in blood flow, whereas genetic heterogeneity is typically ascribed to random mutations. However, evolution within tumors, as in all living systems, is subject to Darwinian principles; thus, it is governed by predictable and reproducible interactions between environmental selection forces and cell phenotype (not genotype). This link between regional variations in environmental properties and cellular adaptive strategies may permit clinical imaging to be used to assess and monitor intratumoral evolution in individual patients. This approach is enabled by new methods that extract, report, and analyze quantitative, reproducible, and mineable clinical imaging data. However, most current quantitative metrics lack spatialness, expressing quantitative radiologic features as a single value for a region of interest encompassing the whole tumor. In contrast, spatially explicit image analysis recognizes that tumors are heterogeneous but not well mixed and defines regionally distinct habitats, some of which appear to harbor tumor populations that are more aggressive and less treatable than others. By identifying regional variations in key environmental selection forces and evidence of cellular adaptation, clinical imaging can enable us to define intratumoral Darwinian dynamics before and during therapy. Advances in image analysis will place clinical imaging in an increasingly central role in the development of evolution-based patient-specific cancer therapy. © RSNA, 2013. PMID:24062559

Gatenby, Robert A; Grove, Olya; Gillies, Robert J

2013-10-01

357

Quantitative trait loci affecting starvation resistance in Drosophila melanogaster.  

PubMed Central

The ability to withstand periods of scarce food resources is an important fitness trait. Starvation resistance is a quantitative trait controlled by multiple interacting genes and exhibits considerable genetic variation in natural populations. This genetic variation could be maintained in the face of strong selection due to a trade-off in resource allocation between reproductive activity and individual survival. Knowledge of the genes affecting starvation tolerance and the subset of genes that affect variation in starvation resistance in natural populations would enable us to evaluate this hypothesis from a quantitative genetic perspective. We screened 933 co-isogenic P-element insertion lines to identify candidate genes affecting starvation tolerance. A total of 383 P-element insertions induced highly significant and often sex-specific mutational variance in starvation resistance. We also used deficiency complementation mapping followed by complementation to mutations to identify 12 genes contributing to variation in starvation resistance between two wild-type strains. The genes we identified are involved in oogenesis, metabolism, and feeding behaviors, indicating a possible link to reproduction and survival. However, we also found genes with cell fate specification and cell proliferation phenotypes, which implies that resource allocation during development and at the cellular level may also influence the phenotypic response to starvation.

Harbison, Susan T; Yamamoto, Akihiko H; Fanara, Juan J; Norga, Koenraad K; Mackay, Trudy F C

2004-01-01

358

Quantitative and functional analysis of a human lymphocyte subset with the T-helper (Leu 3\\/T 4 + ) phenotype and natural killer (NK)-cell characteristics in patients with malignancy  

Microsoft Academic Search

Approximately 20% of normal blood lymphocytes expressing the T-helper (Leu 3\\/T 4+) surface phenotype display natural killer (NK)-like features such as cytoplasmic granules and the ability to bind NK-cell targets. In this study, we have assessed the frequency, phenotypic features, and functional capabilities of such cells in a variety of lymphoid malignancies or solid tumors. In each patient group, the

Andrea Velardi; Loran T. Clement; Carlo E. Grossi

1985-01-01

359

Optofluidic Detection for Cellular Phenotyping  

PubMed Central

Quantitative analysis of the output of processes and molecular interactions within a single cell is highly critical to the advancement of accurate disease screening and personalized medicine. Optical detection is one of the most broadly adapted measurement methods in biological and clinical assays and serves cellular phenotyping. Recently, microfluidics has obtained increasing attention due to several advantages, such as small sample and reagent volumes, very high throughput, and accurate flow control in the spatial and temporal domains. Optofluidics, which is the attempt to integrate optics with microfluidic, shows great promise to enable on-chip phenotypic measurements with high precision, sensitivity, specificity, and simplicity. This paper reviews the most recent developments of optofluidic technologies for cellular phenotyping optical detection.

Tung, Yi-Chung; Huang, Nien-Tsu; Oh, Bo-Ram; Patra, Bishnubrata; Pan, Chi-Chun; Qiu, Teng; Paul, K. Chu; Zhang, Wenjun; Kurabayashi, Katsuo

2012-01-01

360

Quantifying individual variation in behaviour: mixed-effect modelling approaches.  

PubMed

Growing interest in proximate and ultimate causes and consequences of between- and within-individual variation in labile components of the phenotype - such as behaviour or physiology - characterizes current research in evolutionary ecology. The study of individual variation requires tools for quantification and decomposition of phenotypic variation into between- and within-individual components. This is essential as variance components differ in their ecological and evolutionary implications. We provide an overview of how mixed-effect models can be used to partition variation in, and correlations among, phenotypic attributes into between- and within-individual variance components. Optimal sampling schemes to accurately estimate (with sufficient power) a wide range of repeatabilities and key (co)variance components, such as between- and within-individual correlations, are detailed. Mixed-effect models enable the usage of unambiguous terminology for patterns of biological variation that currently lack a formal statistical definition (e.g. 'animal personality' or 'behavioural syndromes'), and facilitate cross-fertilisation between disciplines such as behavioural ecology, ecological physiology and quantitative genetics. PMID:23171297

Dingemanse, Niels J; Dochtermann, Ned A

2012-11-21

361

Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease  

PubMed Central

Neo-Darwinian evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for evolutionary adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

Feinberg, Andrew P.; Irizarry, Rafael A.

2009-01-01

362

Functional genomics complements quantitative genetics in identifying disease-gene associations.  

PubMed

An ultimate goal of genetic research is to understand the connection between genotype and phenotype in order to improve the diagnosis and treatment of diseases. The quantitative genetics field has developed a suite of statistical methods to associate genetic loci with diseases and phenotypes, including quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, each of these approaches have technical and biological shortcomings. For example, the amount of heritable variation explained by GWAS is often surprisingly small and the resolution of many QTL linkage mapping studies is poor. The predictive power and interpretation of QTL and GWAS results are consequently limited. In this study, we propose a complementary approach to quantitative genetics by interrogating the vast amount of high-throughput genomic data in model organisms to functionally associate genes with phenotypes and diseases. Our algorithm combines the genome-wide functional relationship network for the laboratory mouse and a state-of-the-art machine learning method. We demonstrate the superior accuracy of this algorithm through predicting genes associated with each of 1157 diverse phenotype ontology terms. Comparison between our prediction results and a meta-analysis of quantitative genetic studies reveals both overlapping candidates and distinct, accurate predictions uniquely identified by our approach. Focusing on bone mineral density (BMD), a phenotype related to osteoporotic fracture, we experimentally validated two of our novel predictions (not observed in any previous GWAS/QTL studies) and found significant bone density defects for both Timp2 and Abcg8 deficient mice. Our results suggest that the integration of functional genomics data into networks, which itself is informative of protein function and interactions, can successfully be utilized as a complementary approach to quantitative genetics to predict disease risks. All supplementary material is available at http://cbfg.jax.org/phenotype. PMID:21085640

Guan, Yuanfang; Ackert-Bicknell, Cheryl L; Kell, Braden; Troyanskaya, Olga G; Hibbs, Matthew A

2010-11-11

363

Functional Genomics Complements Quantitative Genetics in Identifying Disease-Gene Associations  

PubMed Central

An ultimate goal of genetic research is to understand the connection between genotype and phenotype in order to improve the diagnosis and treatment of diseases. The quantitative genetics field has developed a suite of statistical methods to associate genetic loci with diseases and phenotypes, including quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, each of these approaches have technical and biological shortcomings. For example, the amount of heritable variation explained by GWAS is often surprisingly small and the resolution of many QTL linkage mapping studies is poor. The predictive power and interpretation of QTL and GWAS results are consequently limited. In this study, we propose a complementary approach to quantitative genetics by interrogating the vast amount of high-throughput genomic data in model organisms to functionally associate genes with phenotypes and diseases. Our algorithm combines the genome-wide functional relationship network for the laboratory mouse and a state-of-the-art machine learning method. We demonstrate the superior accuracy of this algorithm through predicting genes associated with each of 1157 diverse phenotype ontology terms. Comparison between our prediction results and a meta-analysis of quantitative genetic studies reveals both overlapping candidates and distinct, accurate predictions uniquely identified by our approach. Focusing on bone mineral density (BMD), a phenotype related to osteoporotic fracture, we experimentally validated two of our novel predictions (not observed in any previous GWAS/QTL studies) and found significant bone density defects for both Timp2 and Abcg8 deficient mice. Our results suggest that the integration of functional genomics data into networks, which itself is informative of protein function and interactions, can successfully be utilized as a complementary approach to quantitative genetics to predict disease risks. All supplementary material is available at http://cbfg.jax.org/phenotype.

Guan, Yuanfang; Ackert-Bicknell, Cheryl L.; Kell, Braden; Troyanskaya, Olga G.; Hibbs, Matthew A.

2010-01-01

364

The GP problem: quantifying gene-to-phenotype relationships.  

PubMed

In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes. PMID:12066839

Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

2002-01-01

365

Phenotypic Variability: Its Components, Measurement and Underlying Developmental Processes  

Microsoft Academic Search

Variability contrasts with variation in that variability describes the potential for variation, not simply the expressed variation.\\u000a The power of studying variability lies in creating a conceptual framework around which the relationship between the genotype\\u000a and phenotype can be understood. Here, we attempt to demonstrate the importance of phenotypic variability, how it structures\\u000a variation, and how fundamental developmental processes structure

Katherine Elizabeth Willmore; Nathan M. Young; Joan T. Richtsmeier

2007-01-01

366

Genetic architecture of regulatory variation in Arabidopsis thaliana.  

PubMed

Studying the genetic regulation of expression variation is a key method to dissect complex phenotypic traits. To examine the genetic architecture of regulatory variation in Arabidopsis thaliana, we performed genome-wide association (GWA) mapping of gene expression in an F(1) hybrid diversity panel. At a genome-wide false discovery rate (FDR) of 0.2, an associated single nucleotide polymorphism (SNP) explains >38% of trait variation. In comparison with SNPs that are distant from the genes to which they were associated, locally associated SNPs are preferentially found in regions with extended linkage disequilibrium (LD) and have distinct population frequencies of the derived alleles (where Arabidopsis lyrata has the ancestral allele), suggesting that different selective forces are acting. Locally associated SNPs tend to have additive inheritance, whereas distantly associated SNPs are primarily dominant. In contrast to results from mapping of expression quantitative trait loci (eQTL) in linkage studies, we observe extensive allelic heterogeneity for local regulatory loci in our diversity panel. By association mapping of allele-specific expression (ASE), we detect a significant enrichment for cis-acting variation in local regulatory variation. In addition to gene expression variation, association mapping of splicing variation reveals both local and distant genetic regulation for intron and exon level traits. Finally, we identify candidate genes for 59 diverse phenotypic traits that were mapped to eQTL. PMID:21467266

Zhang, Xu; Cal, Andrew J; Borevitz, Justin O

2011-04-05

367

Phenotypic Plasticity in the Interactions and Evolution of Species  

Microsoft Academic Search

When individuals of two species interact, they can adjust their phenotypes in response to their respective partner, be they antagonists or mutualists. The reciprocal phenotypic change between individuals of interacting species can reflect an evolutionary response to spatial and temporal variation in species interactions and ecologically result in the structuring of food chains. The evolution of adaptive phenotypic plasticity has

Anurag A. Agrawal

2001-01-01

368

Life history variation in the heavy metal tolerant plant Thlaspi caerulescens growing in a network of contaminated and noncontaminated sites in southern France: role of gene flow, selection and phenotypic plasticity.  

PubMed

* Here we explore life history differences in a set of neighbouring metallicolous and nonmetallicolous populations of the heavy metal tolerant plant Thlaspi caerulescens. * We contrasted data from field observations and from a common garden experiment, in which soil zinc (Zn) concentration and light availability were manipulated, and data on microsatellite molecular variation. * The two ecotypes showed few differences in life history in the field, but large differences in their response to Zn concentration in the common garden. Soil toxicity affected most characters in nonmetallicolous plants, while it had no effect on metallicolous plants. The two ecotypes responded similarly to light. Genetic differentiation for quantitative characters between ecotypes contrasted with the absence of differentiation for microsatellites. Conversely, populations of the same ecotype showed similar responses to Zn, despite their high differentiation for molecular markers. * We conclude that divergent selection related to soil toxicity has had a predominant role in shaping life history differences between ecotypes, gene flow weakly opposing local adaptation despite geographical proximity. PMID:17176406

Jiménez-Ambriz, Georgina; Petit, Christophe; Bourrié, Isabelle; Dubois, Sophie; Olivieri, Isabelle; Ronce, Ophélie

2007-01-01

369

Emerging patterns of epigenomic variation  

PubMed Central

Fuelled by new sequencing technologies, epigenome mapping projects are revealing epigenomic variation at all levels of biological complexity, from species to cells. Comparisons of methylation profiles among species reveal evolutionary conservation of gene body methylation patterns, pointing to the fundamental role of epigenomes in gene regulation. At the human population level, epigenomic changes provide footprints of the effects of genomic variants within the vast non-protein coding fraction of the genome while comparisons of the epigenomes of parents and their offspring point to quantitative epigenomic parent-of-origin effects confounding classical Mendelian genetics. At the organismal level, comparisons of epigenomes from diverse cell types provide insights into cellular differentiation. Finally, comparisons of epigenomes from monozygotic twins help dissect genetic and environmental influences on human phenotypes and longitudinal comparisons reveal aging-associated epigenomic drift. The development of new bioinformatic frameworks for comparative epigenome analysis is putting epigenome maps within reach of researchers across a wide spectrum of biological disciplines.

Milosavljevic, Aleksandar

2011-01-01

370

Genetic and Environmental Contributions to Variation in Baboon Cranial Morphology  

PubMed Central

The development, function, and integration of morphological characteristics are all hypothesized to influence the utility of traits for phylogenetic reconstruction by affecting the way in which morphological characteristics evolve. We use a baboon model to test the hypotheses about phenotypic and quantitative genetic variation of traits in the cranium that bear on a phenotype’s propensity to evolve. We test the hypotheses that: 1) individual traits in different functionally and developmentally defined regions of the cranium are differentially environmentally, genetically, and phenotypically variable; 2) genetic covariance with other traits constrains traits in one region of the cranium more than those in others; 3) and regions of the cranium subject to different levels of mechanical strain differ in the magnitude of variation in individual traits. We find that the levels of environmental and genetic variation in individual traits are randomly distributed across regions of the cranium rather than being structured by developmental origin or degree of exposure to strain. Individual traits in the cranial vault tend to be more constrained by covariance with other traits than those in other regions. Traits in regions subject to high degrees of strain during mastication are not any more variable at any level than other traits. If these results are generalizable to other populations, they indicate that there is no reason to suppose that individual traits from any one part of the cranium are intrinsically less useful for reconstructing patterns of evolution than those from any other part.

Roseman, Charles C.; Willmore, Katherine E.; Rogers, Jeffrey; Hildebolt, Charles; Sadler, Brooke E.; Richtsmeier, Joan T.; Cheverud, James M.

2011-01-01

371

Factors That Contribute to Assay Variation in Quantitative Analysis of Sex Steroid Hormones Using Liquid and Gas Chromatography-Mass Spectrometry  

ERIC Educational Resources Information Center

The list of physiological events in which sex steroids play a role continues to increase. To decipher the roles that sex steroids play in any condition requires high quality cohorts of samples and assays that provide highly accurate quantitative measures. Liquid and gas chromatography coupled with mass spectrometry (LC-MS and GC-MS) have…

Xu, Xia; Veenstra, Timothy D.

2012-01-01

372

Factors That Contribute to Assay Variation in Quantitative Analysis of Sex Steroid Hormones Using Liquid and Gas Chromatography-Mass Spectrometry  

ERIC Educational Resources Information Center

|The list of physiological events in which sex steroids play a role continues to increase. To decipher the roles that sex steroids play in any condition requires high quality cohorts of samples and assays that provide highly accurate quantitative measures. Liquid and gas chromatography coupled with mass spectrometry (LC-MS and GC-MS) have…

Xu, Xia; Veenstra, Timothy D.

2012-01-01

373

Quantitative Trait Associated Microarray Gene Expression Data Analysis  

Microsoft Academic Search

Selection on phenotypes may cause genetic change. To understand the relationship between phenotype and gene expres- sion from an evolutionary viewpoint, it is important to study the concordance between gene expression and profiles of phenotypes. In this study, we use a novel method of clustering to identify genes whose expression profiles are related to a quantitative phenotype. Cluster analysis of

Yi Qu; Shizhong Xu

2006-01-01

374

Behavioral diversity in microbes and low-dimensional phenotypic spaces.  

PubMed

Systematic studies of phenotypic diversity-required for understanding evolution-lag behind investigations of genetic diversity. Here we develop a quantitative approach to studying behavioral diversity, which we apply to swimming of the ciliate Tetrahymena. We measure the full-lifetime behavior of hundreds of individual organisms at high temporal resolution, over several generations and in diverse nutrient conditions. To characterize population diversity and temporal variability we introduce a unique statistical framework grounded in the notion of a phenotypic space of behaviors. We show that this space is effectively low dimensional with dimensions that correlate with a two-state "roaming and dwelling" model of swimming behavior. Temporal variability over the lifetime of an individual is correlated with the fraction of time spent roaming whereas diversity between individuals is correlated with the speed of roaming. Quantifying the dynamics of behavioral variation shows that behavior over the lifetime of an individual is strongly nonstationary. Analysis of behavioral dynamics between generations reveals complex patterns of behavioral heritability that point to the importance of considering correlations beyond mothers and daughters. Our description of a low-dimensional behavioral space should enable the systematic study of the evolutionary and ecological bases of phenotypic constraints. Future experimental and theoretical studies of behavioral diversity will have to account for the possibility of nonstationary and environmentally dependent behavioral dynamics that we observe. PMID:23898201

Jordan, David; Kuehn, Seppe; Katifori, Eleni; Leibler, Stanislas

2013-07-29

375

Developmental Quantitative Genetics, Conditional Epigenetic Variability and Growth in Mice  

PubMed Central

Ontogenetic variation in the causal components of phenotypic variability and covariability is described for body weight and tail length in mice derived from a full 7 X 7 diallel cross. Age-related changes in additive, dominance, sex-linked and maternal variance and covariance between 14 and 70 days of age are described. Age-specific variance components at time t are conditioned on the causal genetic effects at time (t - 1). This procedure demonstrates the generation of significant episodes of new genetic variation arising at specific intervals during ontogeny. These episodes of new genetic variation are placed in the context of epigenetic models in developmental quantitative genetics. These results are also concordant on recent findings on age-specific gene expression in mouse growth as shown by QTL analyses.

Atchley, W. R.; Zhu, J.

1997-01-01

376

Characterizing phenotype with tracer based metabolomics  

Microsoft Academic Search

In the post-genomic era, a pressing challenge to biological scientists is to understand the organization of gene functions,\\u000a the interaction between gene and nutrient environment, and the genesis of phenotypes. Metabolomics, the quantitation of low\\u000a molecular weight compounds, has been used to provide a phenotypic description of a cell or tissue by a set of metabolites.\\u000a Gene function is hypothesized

Wai Nang P. Lee; P. Lee

2006-01-01

377

Genetically altered mice: phenotypes, no phenotypes, and Faux phenotypes  

Microsoft Academic Search

Phenotype’ means different things, but whatever the measure, phenotype can be profoundly influenced by genetic, environmental and infectious variables. The laboratory mouse is a complex multisystemic organism which, despite its genetically inbred nature, as highly variable pathophysiologic characteristics. Mouse strains have background characteristics that can influence genomics research. In addition to the mouse itself, different approaches toward creating mutant mice

Stephen W. Barthold

2004-01-01

378

Phenotypic and Evolutionary Consequences of Social Behaviours: Interactions among Individuals Affect Direct Genetic Effects  

PubMed Central

Traditional quantitative genetics assumes that an individual's phenotype is determined by both genetic and environmental factors. For many animals, part of the environment is social and provided by parents and other interacting partners. When expression of genes in social partners affects trait expression in a focal individual, indirect genetic effects occur. In this study, we explore the effects of indirect genetic effects on the magnitude and range of phenotypic values in a focal individual in a multi-member model analyzing three possible classes of interactions between individuals. We show that social interactions may not only cause indirect genetic effects but can also modify direct genetic effects. Furthermore, we demonstrate that both direct and indirect genetic effects substantially alter the range of phenotypic values, particularly when a focal trait can influence its own expression via interactions with traits in other individuals. We derive a function predicting the relative importance of direct versus indirect genetic effects. Our model reveals that both direct and indirect genetic effects can depend to a large extent on both group size and interaction strength, altering group mean phenotype and variance. This may lead to scenarios where between group variation is much higher than within group variation despite similar underlying genetic properties, potentially affecting the level of selection. Our analysis highlights key properties of indirect genetic effects with important consequences for trait evolution, the level of selection and potentially speciation.

Trubenova, Barbora; Hager, Reinmar

2012-01-01

379

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