Genetic analyses using GGE model and a mixed linear model approach, and stability analyses using AMMI bi-plot for late-maturity alpha-amylase activity in bread wheat genotypes.

PubMed

Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Fofana, Bourlaye

2017-06-01

Low falling number and discounting grain when it is downgraded in class are the consequences of excessive late-maturity α-amylase activity (LMAA) in bread wheat (Triticum aestivum L.). Grain expressing high LMAA produces poorer quality bread products. To effectively breed for low LMAA, it is necessary to understand what genes control it and how they are expressed, particularly when genotypes are grown in different environments. In this study, an International Collection (IC) of 18 spring wheat genotypes and another set of 15 spring wheat cultivars adapted to South Dakota (SD), USA were assessed to characterize the genetic component of LMAA over 5 and 13 environments, respectively. The data were analysed using a GGE model with a mixed linear model approach and stability analysis was presented using an AMMI bi-plot on R software. All estimated variance components and their proportions to the total phenotypic variance were highly significant for both sets of genotypes, which were validated by the AMMI model analysis. Broad-sense heritability for LMAA was higher in SD adapted cultivars (53%) compared to that in IC (49%). Significant genetic effects and stability analyses showed some genotypes, e.g. 'Lancer', 'Chester' and 'LoSprout' from IC, and 'Alsen', 'Traverse' and 'Forefront' from SD cultivars could be used as parents to develop new cultivars expressing low levels of LMAA. Stability analysis using an AMMI bi-plot revealed that 'Chester', 'Lancer' and 'Advance' were the most stable across environments, while in contrast, 'Kinsman', 'Lerma52' and 'Traverse' exhibited the lowest stability for LMAA across environments.

Atlantic salmon Salmo salar in the chalk streams of England are genetically unique.

PubMed

Ikediashi, C; Paris, J R; King, R A; Beaumont, W R C; Ibbotson, A; Stevens, J R

2018-03-01

Recent research has identified genetic groups of Atlantic salmon Salmo salar that show association with geological and environmental boundaries. This study focuses on one particular subgroup of the species inhabiting the chalk streams of southern England, U.K. These fish are genetically distinct from other British and European S. salar populations and have previously demonstrated markedly low admixture with populations in neighbouring regions. The genetic population structure of S. salar occupying five chalk streams was explored using 16 microsatellite loci. The analysis provides evidence of the genetic distinctiveness of chalk-stream S. salar in southern England, in comparison with populations from non-chalk regions elsewhere in western Europe. Little genetic differentiation exists between the chalk-stream populations and a pattern of isolation by distance was evident. Furthermore, evidence of temporal stability of S. salar populations across the five chalk streams was found. This work provides new insights into the temporal stability and lack of genetic population sub-structuring within a unique component of the species' range of S. salar. © 2018 The Fisheries Society of the British Isles.

Heritable influences on behavioural problems from early childhood to mid-adolescence: evidence for genetic stability and innovation.

PubMed

Lewis, G J; Plomin, R

2015-07-01

Although behavioural problems (e.g., anxiety, conduct, hyperactivity, peer problems) are known to be heritable both in early childhood and in adolescence, limited work has examined prediction across these ages, and none using a genetically informative sample. We examined, first, whether parental ratings of behavioural problems (indexed by the Strengths and Difficulties questionnaire) at ages 4, 7, 9, 12, and 16 years were stable across these ages. Second, we examined the extent to which stability reflected genetic or environmental effects through multivariate quantitative genetic analysis on data from a large (n > 3000) population (UK) sample of monozygotic and dizygotic twins. Behavioural problems in early childhood (age 4 years) showed significant associations with the corresponding behavioural problem at all subsequent ages. Moreover, stable genetic influences were observed across ages, indicating that biological bases underlying behavioural problems in adolescence are underpinned by genetic influences expressed as early as age 4 years. However, genetic and environmental innovations were also observed at each age. These observations indicate that genetic factors are important for understanding stable individual differences in behavioural problems across childhood and adolescence, although novel genetic influences also facilitate change in such behaviours.

Genome-Wide Analysis of Grain Yield Stability and Environmental Interactions in a Multiparental Soybean Population.

PubMed

Xavier, Alencar; Jarquin, Diego; Howard, Reka; Ramasubramanian, Vishnu; Specht, James E; Graef, George L; Beavis, William D; Diers, Brian W; Song, Qijian; Cregan, Perry B; Nelson, Randall; Mian, Rouf; Shannon, J Grover; McHale, Leah; Wang, Dechun; Schapaugh, William; Lorenz, Aaron J; Xu, Shizhong; Muir, William M; Rainey, Katy M

2018-02-02

Genetic improvement toward optimized and stable agronomic performance of soybean genotypes is desirable for food security. Understanding how genotypes perform in different environmental conditions helps breeders develop sustainable cultivars adapted to target regions. Complex traits of importance are known to be controlled by a large number of genomic regions with small effects whose magnitude and direction are modulated by environmental factors. Knowledge of the constraints and undesirable effects resulting from genotype by environmental interactions is a key objective in improving selection procedures in soybean breeding programs. In this study, the genetic basis of soybean grain yield responsiveness to environmental factors was examined in a large soybean nested association population. For this, a genome-wide association to performance stability estimates generated from a Finlay-Wilkinson analysis and the inclusion of the interaction between marker genotypes and environmental factors was implemented. Genomic footprints were investigated by analysis and meta-analysis using a recently published multiparent model. Results indicated that specific soybean genomic regions were associated with stability, and that multiplicative interactions were present between environments and genetic background. Seven genomic regions in six chromosomes were identified as being associated with genotype-by-environment interactions. This study provides insight into genomic assisted breeding aimed at achieving a more stable agronomic performance of soybean, and documented opportunities to exploit genomic regions that were specifically associated with interactions involving environments and subpopulations. Copyright © 2018 Xavier et al.

Longitudinal Genetic Analysis of Early Reading: The Western Reserve Reading Project

ERIC Educational Resources Information Center

Petrill, Stephen A.; Deater-Deckard, Kirby; Thompson, Lee Anne; Schatschneider, Chris; DeThorne, Laura S.; Vandenbergh, David J.

2007-01-01

We examined the genetic and environmental contribution to the stability and instability of reading outcomes in early elementary school using a sample of 283 twin pairs drawn from the Western Reserve Reading Project. Twins were assessed across two measurement occasions. In Wave 1, children were either in kindergarten or first grade. Wave 2…

Persistence and innovation effects in genetic and environmental factors in negative emotionality during infancy: A twin study.

PubMed

Schumann, Lyndall; Boivin, Michel; Paquin, Stéphane; Lacourse, Eric; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E; Booij, Linda

2017-01-01

Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait's interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology.

Mutation scanning in a single and a stacked genetically modified (GM) event by real-time PCR and high resolution melting (HRM) analysis.

PubMed

Ben Ali, Sina-Elisabeth; Madi, Zita Erika; Hochegger, Rupert; Quist, David; Prewein, Bernhard; Haslberger, Alexander G; Brandes, Christian

2014-10-31

Genetic mutations must be avoided during the production and use of seeds. In the European Union (EU), Directive 2001/18/EC requires any DNA construct introduced via transformation to be stable. Establishing genetic stability is critical for the approval of genetically modified organisms (GMOs). In this study, genetic stability of two GMOs was examined using high resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) employing Scorpion primers for amplification. The genetic variability of the transgenic insert and that of the flanking regions in a single oilseed rape variety (GT73) and a stacked maize (MON88017×MON810) was studied. The GT73 and the 5' region of MON810 showed no instabilities in the examined regions. However; two out of 100 analyzed samples carried a heterozygous point mutation in the 3' region of MON810 in the stacked variety. These results were verified by direct sequencing of the amplified PCR products as well as by sequencing of cloned PCR fragments. The occurrence of the mutation suggests that the 5' region is more suitable than the 3' region for the quantification of MON810. The identification of the single nucleotide polymorphism (SNP) in a stacked event is in contrast to the results of earlier studies of the same MON810 region in a single event where no DNA polymorphism was found.

The influence of genetic drift and selection on quantitative traits in a plant pathogenic fungus.

PubMed

Stefansson, Tryggvi S; McDonald, Bruce A; Willi, Yvonne

2014-01-01

Genetic drift and selection are ubiquitous evolutionary forces acting to shape genetic variation in populations. While their relative importance has been well studied in plants and animals, less is known about their relative importance in fungal pathogens. Because agro-ecosystems are more homogeneous environments than natural ecosystems, stabilizing selection may play a stronger role than genetic drift or diversifying selection in shaping genetic variation among populations of fungal pathogens in agro-ecosystems. We tested this hypothesis by conducting a QST/FST analysis using agricultural populations of the barley pathogen Rhynchosporium commune. Population divergence for eight quantitative traits (QST) was compared with divergence at eight neutral microsatellite loci (FST) for 126 pathogen strains originating from nine globally distributed field populations to infer the effects of genetic drift and types of selection acting on each trait. Our analyses indicated that five of the eight traits had QST values significantly lower than FST, consistent with stabilizing selection, whereas one trait, growth under heat stress (22°C), showed evidence of diversifying selection and local adaptation (QST>FST). Estimates of heritability were high for all traits (means ranging between 0.55-0.84), and average heritability across traits was negatively correlated with microsatellite gene diversity. Some trait pairs were genetically correlated and there was significant evidence for a trade-off between spore size and spore number, and between melanization and growth under benign temperature. Our findings indicate that many ecologically and agriculturally important traits are under stabilizing selection in R. commune and that high within-population genetic variation is maintained for these traits.

Stability analysis via the concept of Lyapunov exponents: a case study in optimal controlled biped standing

NASA Astrophysics Data System (ADS)

Sun, Yuming; Wu, Christine Qiong

2012-12-01

Balancing control is important for biped standing. In spite of large efforts, it is very difficult to design balancing control strategies satisfying three requirements simultaneously: maintaining postural stability, improving energy efficiency and satisfying the constraints between the biped feet and the ground. In this article, a proportional-derivative (PD) controller is proposed for a standing biped, which is simplified as a two-link inverted pendulum with one additional rigid foot-link. The genetic algorithm (GA) is used to search for the control gain meeting all three requirements. The stability analysis of such a deterministic biped control system is carried out using the concept of Lyapunov exponents (LEs), based on which, the system stability, where the disturbance comes from the initial states, and the structural stability, where the disturbance comes from the PD gains, are examined quantitively in terms of stability region. This article contributes to the biped balancing control, more significantly, the method shown in the studied case of biped provides a general framework of systematic stability analysis for certain deterministic nonlinear dynamical systems.

Persistence and innovation effects in genetic and environmental factors in negative emotionality during infancy: A twin study

PubMed Central

Boivin, Michel; Paquin, Stéphane; Lacourse, Eric; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E.; Booij, Linda

2017-01-01

Background Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. Method Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. Results There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait’s interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. Conclusions In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology. PMID:28448561

Resolving the evolutionary paradox of genetic instability: a cost-benefit analysis of DNA repair in changing environments.

PubMed

Breivik, Jarle; Gaudernack, Gustav

2004-04-09

Loss of genetic stability is a critical phenomenon in cancer and antibiotic resistance, and the prevailing dogma is that unstable cells survive because instability provides adaptive mutations. Challenging this view, we have argued that genetic instability arises because DNA repair may be a counterproductive strategy in mutagenic environments. This paradoxical relationship has also been confirmed by explicit experiments, but the underlying evolutionary principles remain controversial. This paper aims to clarify the issue, and presents a model that explains genetic instability from the basic perspective of molecular evolution and information processing.

Analysis of genetic stability at SSR loci during somatic embryogenesis in maritime pine (Pinus pinaster).

PubMed

Marum, Liliana; Rocheta, Margarida; Maroco, João; Oliveira, M Margarida; Miguel, Célia

2009-04-01

Somatic embryogenesis (SE) is a propagation tool of particular interest for accelerating the deployment of new high-performance planting stock in multivarietal forestry. However, genetic conformity in in vitro propagated plants should be assessed as early as possible, especially in long-living trees such as conifers. The main objective of this work was to study such conformity based on genetic stability at simple sequence repeat (SSR) loci during somatic embryogenesis in maritime pine (Pinus pinaster Ait.). Embryogenic cell lines (ECLs) subjected to tissue proliferation during 6, 14 or 22 months, as well as emblings regenerated from several ECLs, were analyzed. Genetic variation at seven SSR loci was detected in ECLs under proliferation conditions for all time points, and in 5 out of 52 emblings recovered from somatic embryos. Three of these five emblings showed an abnormal phenotype consisting mainly of plagiotropism and loss of apical dominance. Despite the variation found in somatic embryogenesis-derived plant material, no correlation was established between genetic stability at the analyzed loci and abnormal embling phenotype, present in 64% of the emblings. The use of microsatellites in this work was efficient for monitoring mutation events during the somatic embryogenesis in P. pinaster. These molecular markers should be useful in the implementation of new breeding and deployment strategies for improved trees using SE.

Genetic stability assessment of wWasabi plants regenerated from long-term cryopreserved shoot tips using morphological, biochemical and molecular analysis.

PubMed

Matsumoto, Toshikazu; Akihiro, Takashi; Maki, Shinya; Mochida, Kouhei; Kitagawa, Masaru; Tanaka, Daisuke; Yamamoto, Shin-Ichi; Niino, Takao

2013-01-01

This study compared the effect of cryopreserved storage duration of wasabi shoot tips, which derived from the same in vitro mother-plant. We compared the survival of shoot tips and the genetic stability of regenerated plants originating from four experimental groups: shoot tips stored in a -150°C deep-freezer for 10 years; shoot tips stored in liquid nitrogen for 2 h; shoot tips treated with PVS2 vitrification solution; and untreated controls. No significant difference in survival was observed between the four experimental groups. Survival ranged between 93 and 100%. Genetic stability of plants regenerated from cryopreserved shoot tips was assessed over a period of 24 months using morphological, biochemical and molecular markers. While glucose, fructose and glutamic acid concentrations differed slightly between experimental groups after 16 months, these differences disappeared after 24 months. No significant differences were noted for the morphological markers studied (petiole length, shoot number and leaf index). No differences were observed in RAPD profiles obtained with the six primers tested.

Mutation Scanning in a Single and a Stacked Genetically Modified (GM) Event by Real-Time PCR and High Resolution Melting (HRM) Analysis

PubMed Central

Ben Ali, Sina-Elisabeth; Madi, Zita Erika; Hochegger, Rupert; Quist, David; Prewein, Bernhard; Haslberger, Alexander G.; Brandes, Christian

2014-01-01

Genetic mutations must be avoided during the production and use of seeds. In the European Union (EU), Directive 2001/18/EC requires any DNA construct introduced via transformation to be stable. Establishing genetic stability is critical for the approval of genetically modified organisms (GMOs). In this study, genetic stability of two GMOs was examined using high resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) employing Scorpion primers for amplification. The genetic variability of the transgenic insert and that of the flanking regions in a single oilseed rape variety (GT73) and a stacked maize (MON88017 × MON810) was studied. The GT73 and the 5' region of MON810 showed no instabilities in the examined regions. However; two out of 100 analyzed samples carried a heterozygous point mutation in the 3' region of MON810 in the stacked variety. These results were verified by direct sequencing of the amplified PCR products as well as by sequencing of cloned PCR fragments. The occurrence of the mutation suggests that the 5' region is more suitable than the 3' region for the quantification of MON810. The identification of the single nucleotide polymorphism (SNP) in a stacked event is in contrast to the results of earlier studies of the same MON810 region in a single event where no DNA polymorphism was found. PMID:25365178

High stability of yellow fever 17D-204 vaccine: a 12-year restrospective analysis of large-scale production.

PubMed

Barban, V; Girerd, Y; Aguirre, M; Gulia, S; Pétiard, F; Riou, P; Barrere, B; Lang, J

2007-04-12

We have retrospectively analyzed 12 bulk lots of yellow fever vaccine Stamaril, produced between 1990 and 2002 and prepared from the same seed lot that has been in continuous use since 1990. All vaccine batches displayed identical genome sequence. Only four nucleotide substitutions were observed, compared to previously published sequence, with no incidence at amino-acid level. Fine analysis of viral plaque size distribution was used as an additional marker for genetic stability and demonstrated a remarkable homogeneity of the viral population. The total virus load, measured by qRT-PCR, was also homogeneous pointing out reproducibility of the vaccine production process. Mice inoculated intracerebrally with the different bulks exhibited a similar average survival time, and ratio between in vitro potency and mouse LD(50) titers remained constant from batch-to-batch. Taken together, these data demonstrate the genetic stability of the strain at mass production level over a period of 12 years and reinforce the generally admitted idea of the safety of YF17D-based vaccines.

RAPD and ISSR based evaluation of genetic stability of micropropagated plantlets of Morus alba L. variety S-1

PubMed Central

Saha, Soumen; Adhikari, Sinchan; Dey, Tulsi; Ghosh, Parthadeb

2015-01-01

Plant regeneration through rapid in vitro clonal propagation of nodal explants of Morus alba L. variety S-1 was established along with genetic stability analysis of regenerates. Axillary shoot bud proliferation was achieved on Murashige and Skoog (MS) medium in various culture regimes. Highest number of shoots (5.62 ± 0.01), with average length 4.19 ± 0.01 cm, was initially achieved with medium containing 0.5 mg/l N6-benzyladenine (BA) and 3% sucrose. Repeated subculturing of newly formed nodal parts after each harvest up to sixth passage, yielded highest number of shoots (about 32.27) per explants was obtained after fourth passage. Rooting of shoots occurred on 1/2 MS medium supplemented with 1.0 mg/1 Indole-3-butyric acid (IBA). About 90% (89.16) of the plantlets transferred to the mixture of sand:soil:organic manure (2:2:1) in small plastic pots acclimatized successfully. Genetic stability of the discussed protocol was confirmed by two DNA-based fingerprinting techniques i.e. RAPD (random amplified polymorphic DNA) and ISSR (inter-simple sequence repeat). This protocol can be used for commercial propagation and for future genetic improvement studies. PMID:26693403

Parent- and child-driven effects during the transition to adolescence: a longitudinal, genetic analysis of the home environment.

PubMed

Hannigan, Laurie J; McAdams, Tom A; Plomin, Robert; Eley, Thalia C

2017-09-01

Theoretical models of child development typically consider the home environment as a product of bidirectional effects, with parent- and child-driven processes operating interdependently. However, the developmental structure of these processes during the transition from childhood to adolescence has not been well studied. In this study we used longitudinal genetic analyses of data from 6646 UK-representative twin pairs (aged 9-16 years) to investigate stability and change in parenting and household chaos in the context of parent-child bidirectional effects. Stability in the home environment was modest, arising mainly from parent-driven processes and family-wide influences. In contrast, change over time was more influenced by child-driven processes, indicated by significant age-specific genetic influences. Interpretations of these results and their implications for researchers are discussed. © 2016 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Word Reading Fluency: Role of Genome-Wide Single-Nucleotide Polymorphisms in Developmental Stability and Correlations with Print Exposure

ERIC Educational Resources Information Center

Harlaar, Nicole; Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

2014-01-01

The genetic effects on individual differences in reading development were examined using genome-wide complex trait analysis (GCTA) in a twin sample. In unrelated individuals (one twin per pair, n = 2,942), the GCTA-based heritability of reading fluency was ~20%-29% at ages 7 and 12. GCTA bivariate results showed that the phenotypic stability of…

Evolutionary institutionalism.

PubMed

Fürstenberg, Dr Kai

Institutions are hard to define and hard to study. Long prominent in political science have been two theories: Rational Choice Institutionalism (RCI) and Historical Institutionalism (HI). Arising from the life sciences is now a third: Evolutionary Institutionalism (EI). Comparative strengths and weaknesses of these three theories warrant review, and the value-to-be-added by expanding the third beyond Darwinian evolutionary theory deserves consideration. Should evolutionary institutionalism expand to accommodate new understanding in ecology, such as might apply to the emergence of stability, and in genetics, such as might apply to political behavior? Core arguments are reviewed for each theory with more detailed exposition of the third, EI. Particular attention is paid to EI's gene-institution analogy; to variation, selection, and retention of institutional traits; to endogeneity and exogeneity; to agency and structure; and to ecosystem effects, institutional stability, and empirical limitations in behavioral genetics. RCI, HI, and EI are distinct but complementary. Institutional change, while amenable to rational-choice analysis and, retrospectively, to criticaljuncture and path-dependency analysis, is also, and importantly, ecological. Stability, like change, is an emergent property of institutions, which tend to stabilize after change in a manner analogous to allopatric speciation. EI is more than metaphorically biological in that institutional behaviors are driven by human behaviors whose evolution long preceded the appearance of institutions themselves.

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress

PubMed Central

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association (r2 = 0.3–0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association (P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H9 will help us to identify significant loci and alleles that made H9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions. PMID:28878785

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress.

PubMed

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H 9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association ( r 2 = 0.3-0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association ( P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H 9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H 9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H 9 will help us to identify significant loci and alleles that made H 9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions.

Survival and genetic stability of Dendranthema grandiflora Tzvelev shoot apices after cryopreservation by vitrification and encapsulation-dehydration.

PubMed

Martín, Carmen; González-Benito, M Elena

2005-12-01

The aim of this study was to compare the genetic stability of chrysanthemum (cv. Pasodoble) apices cryopreserved using two different methods: encapsulation-dehydration and vitrification. The assessment of the genetic stability was developed using RAPDs markers. Assessment of stability was evaluated in pot-cultivated mother plants (from which buds were excised for micropropagation), in shoots (leave tissue) from which apices were extracted for cryopreservation, and in shoots regenerated from cryopreserved apices 30 days after recovery and after further 3 months in culture. Throughout the process the origin of the apices (in vitro-shoot from which they were excised) was recorded. Twenty one regenerants cryopreserved by vitrification and 25 by encapsulation-dehydration were assessed. Only one cryopreserved regenerant from the encapsulation-dehydration method showed a different band pattern. These results support the necessity of monitoring the genetic stability of the regenerants obtained after cryopreservation, as this is a very useful technique for the conservation of plant genetic resources.

Longitudinal stability of cognitive ability from infancy to early childhood: genetic and environmental etiologies.

PubMed

LaBuda, M C; DeFries, J C; Plomin, R; Fulker, D W

1986-10-01

A path model of genetic and shared family environmental transmission was fitted to general cognitive ability data from 1-, 2-, 3-, and 4-year-old adopted and nonadopted children and their parents in order to assess the etiology of longitudinal stability from infancy to early childhood. Stability across years is moderate and is due mainly to influences not predicted by parental IQ. Results of the present study, in conjunction with those of previous twin studies, suggest substantial genetic stability from infancy and early childhood to adulthood.

Clinical and Molecular Consequences of NF1 Microdeletion

DTIC Science & Technology

2006-05-01

service based on meta -PCR/sequencing, dosage analysis , and loss of heterozygosity analysis . Genet Test 2004;8(4):368-80. 51. Kluwe L, Mautner VF. Mosaicism...neurofibromin in normal centrosome function and in maintaining genome stability. Our detailed analysis of human and chimpanzee genome sequences were...chromosomes and DNA fibers (1). Tandem duplication of the region would have significant impact on many aspects of NF1 research, e.g., mutational analysis

Hemiclonal analysis reveals significant genetic, environmental and genotype x environment effects on sperm size in Drosophila melanogaster.

PubMed

Morrow, E H; Leijon, A; Meerupati, A

2008-11-01

Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.

Sources of Contradictions in the Evaluation of Population Genetic Consequences after the Chernobyl Disaster

PubMed Central

Glazko, V.I.; Glazko, T.T.

2013-01-01

The review covers the analysis of our own and published data pertaining to population and genetic consequences in various mammalian species under conditions of high levels of ionizing radiation as a result of the Chernobyl accident. The findings indicate that these conditions have promoted the reproduction of heterozygotes in polyloci spectra of molecular genetic markers and animals with a relatively increased stability of the chromosomal apparatus. The prospects of using the reproductive “success” of the carriers of these characteristics as an integral indicator of the selective influence of environmental stress factors are discussed. PMID:23556130

Sources of contradictions in the evaluation of population genetic consequences after the chernobyl disaster.

PubMed

Glazko, V I; Glazko, T T

2013-01-01

The review covers the analysis of our own and published data pertaining to population and genetic consequences in various mammalian species under conditions of high levels of ionizing radiation as a result of the Chernobyl accident. The findings indicate that these conditions have promoted the reproduction of heterozygotes in polyloci spectra of molecular genetic markers and animals with a relatively increased stability of the chromosomal apparatus. The prospects of using the reproductive "success" of the carriers of these characteristics as an integral indicator of the selective influence of environmental stress factors are discussed.

Stability and Response of Polygenic Traits to Stabilizing Selection and Mutation

PubMed Central

de Vladar, Harold P.; Barton, Nick

2014-01-01

When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are equivalent. Furthermore, the genetic variance that is maintained by mutation–selection balance is 2μ/S per locus, where μ is the mutation rate and S the strength of stabilizing selection. In reality, alleles vary in their effects, making the fitness landscape asymmetric and complicating analysis of the equilibria. We show that that the resulting genetic variance depends on the fraction of alleles near fixation, which contribute by 2μ/S, and on the total mutational effects of alleles that are at intermediate frequency. The interplay between stabilizing selection and mutation leads to a sharp transition: alleles with effects smaller than a threshold value of 2μ/S remain polymorphic, whereas those with larger effects are fixed. The genetic load in equilibrium is less than for traits of equal effects, and the fitness equilibria are more similar. We find that if the optimum is displaced, alleles with effects close to the threshold value sweep first, and their rate of increase is bounded by μS. Long-term response leads in general to well-adapted traits, unlike the case of equal effects that often end up at a suboptimal fitness peak. However, the particular peaks to which the populations converge are extremely sensitive to the initial states and to the speed of the shift of the optimum trait value. PMID:24709633

[Clonal micropropagation of a rare species Hedysarum theinum Krasnob (Fabaceae) and assessment of the genetic stability of regenerated plants using ISSR markers].

PubMed

Erst, A A; Svyagina, N S; Novikova, T I; Dorogina, O V

2015-02-01

In the present study, a protocol was developed for the in vitro propagation of a rare medicinal plant, Hedysarum theinum (tea sweetvetch), from axillary buds, and identification of the regenerants was performed with the use of ISSR markers. It was demonstrated that Gamborg and Eveleigh medium supplemented with 5 μM 6-benzylaminopurine was the best for H. theinum for initial multiplication. On the other hand, half-strength Murashige and Skoog (MS) basal medium supplemented with 7 μM α-naphthaleneacetic acid proved to be the best for explant rooting. Molecular genetic analysis of the H. theinum mother plants and the obtained regenerants was performed with six ISSR markers. Depending on the primer, four to ten amplified fragments with sizes ranging from 250 to 3000 bp were identified. Our results confirmed the genetic stability of regenerants obtained in five passages and their identity to the mother plant.

[Research progress on mutation by spaceflight in medicinal plants breeding].

PubMed

Yan, Shuo; Gao, Wenyuan; Lu, Fuping; Zhao, Runhuai

2010-02-01

Space breeding in medicinal plants is special characteristics in China. Compared with other plants, in spite of a relatively small number, Medicinal plants have more obvious characteristics and advantages. Research on medicinal plants has also been carried into all aspects, such as biological traits, physiology and biochemistry, genomics, as well as differences in chemical composition, and chemical composition analysis is also involved. However, compared with other plants, especially crops and vegetables, biological research is an obvious deficiency, that is mainly reflected in the insufficient genetics and breeding researches, the stability of genetic traits from generation to generation were not followed up and in-depth study in breeding areas was not carried out. If medicinal plants resources from space with the genetic stability good quality were selected, it would address the problem of lack of resources and ease the pressure on wild resources of medicinal plants. It would at the same time play an important role in promoting the development of medicinal botany space breeding and the implementation of modernization of traditional Chinese medicine.

Longitudinal Stability in Genetic Effects on Children's Conversational Language Productivity

ERIC Educational Resources Information Center

DeThorne, Laura Segebart; Harlaar, Nicole; Petrill, Stephen A.; Deater-Deckard, Kirby

2012-01-01

Purpose: The authors examined the longitudinal stability of genetic and environmental influences on children's productive language sample measures during the early school-age years. Method: Twin study methodology with structural equation modeling was used to derive univariate estimates of additive genetic (A), shared environmental (C), and…

Automatic generation of the non-holonomic equations of motion for vehicle stability analysis

NASA Astrophysics Data System (ADS)

Minaker, B. P.; Rieveley, R. J.

2010-09-01

The mathematical analysis of vehicle stability has been utilised as an important tool in the design, development, and evaluation of vehicle architectures and stability controls. This paper presents a novel method for automatic generation of the linearised equations of motion for mechanical systems that is well suited to vehicle stability analysis. Unlike conventional methods for generating linearised equations of motion in standard linear second order form, the proposed method allows for the analysis of systems with non-holonomic constraints. In the proposed method, the algebraic constraint equations are eliminated after linearisation and reduction to first order. The described method has been successfully applied to an assortment of classic dynamic problems of varying complexity including the classic rolling coin, the planar truck-trailer, and the bicycle, as well as in more recent problems such as a rotor-stator and a benchmark road vehicle with suspension. This method has also been applied in the design and analysis of a novel three-wheeled narrow tilting vehicle with zero roll-stiffness. An application for determining passively stable configurations using the proposed method together with a genetic search algorithm is detailed. The proposed method and software implementation has been shown to be robust and provides invaluable conceptual insight into the stability of vehicles and mechanical systems.

DNA in soil: adsorption, genetic transformation, molecular evolution and genetic microchip.

PubMed

Trevors, J T

1996-07-01

This review examines interactions between DNA and soil with an emphasis on the persistence and stability of DNA in soil. The role of DNA in genetic transformation in soil microorganisms will also be discussed. In addition, a postulated mechanism for stabilization and elongation/assembly of primitive genetic material and the role of soil particles, salt concentrations, temperature cycling and crystal formation is examined.

Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment.

PubMed

Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

2015-07-03

Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range.

Genetic and Environmental Stability Differs in Reactive and Proactive Aggression

PubMed Central

Tuvblad, Catherine; Raine, Adrian; Zheng, Mo; Baker, Laura A.

2009-01-01

The aim of this study was to examine stability and change in genetic and environmental influences on reactive (impulsive and affective) and proactive (planned and instrumental) aggression from childhood to early adolescence. The sample was drawn from an ongoing longitudinal twin study of risk factors for antisocial behavior at the University of Southern California (USC). The twins were measured on two occasions: ages 9–10 years (N = 1,241) and 11–14 years (N = 874). Reactive and proactive aggressive behaviors were rated by parents. The stability in reactive aggression was due to genetic and nonshared environmental influences, whereas the continuity in proactive aggression was primarily genetically mediated. Change in both reactive and proactive aggression between the two occasions was mainly explained by nonshared environmental influences, although some evidence for new genetic variance at the second occasion was found for both forms of aggression. These results suggest that proactive and reactive aggression differ in their genetic and environmental stability, and provide further evidence for some distinction between reactive and proactive forms of aggression. PMID:19688841

Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

PubMed Central

Vangestel, Carl; Mergeay, Joachim; Dawson, Deborah A.; Vandomme, Viki; Lens, Luc

2011-01-01

Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed. PMID:21747940

Stability in and correlation between factors influencing genetic quality of seed lots in seed orchard of Pinus tabuliformis Carr. over a 12-year span.

PubMed

Li, Wei; Wang, Xiaoru; Li, Yue

2011-01-01

Coniferous seed orchards require a long period from initial seed harvest to stable seed production. Differential reproductive success and asynchrony are among the main factors for orchard crops year-to-year variation in terms of parental gametic contribution and ultimately the genetic gain. It is fundamental in both making predictions about the genetic composition of the seed crop and decisions about orchard roguing and improved seed orchard establishment. In this paper, a primary Chinese pine seed orchard with 49 clones is investigated for stability, variation and correlation analysis of factors which influence genetic quality of the seed lots from initial seed harvest to the stable seed production over a 12 years span. Results indicated that the reproductive synchrony index of pollen shedding has shown to be higher than that of the strobili receptivity, and both can be drastically influenced by the ambient climate factors. Reproductive synchrony index of the clones has certain relative stability and it could be used as an indication of the seed orchard status during maturity stage; clones in the studied orchard have shown extreme differences in terms of the gametic and genetic contribution to the seed crop at the orchard's early production phase specifically when they severe as either female or male parents. Those differences are closely related to clonal sex tendency at the time of orchard's initial reproduction. Clonal gamete contribution as male and female parent often has a negative correlation. Clone utilization as pollen, seed or both pollen and seed donors should consider the role it would play in the seed crop; due to numerous factors influencing on the mating system in seed orchards, clonal genetic contribution as male parent is uncertain, and it has major influence on the genetic composition in the seed orchard during the initial reproductive and seed production phase.

[Use of multiple locus variable number tandem repeats analysis for the Brucella systematization].

PubMed

Kulakov, Iu K; Kovalev, D A; Misetova, E N; Golovneva, S I; Liapustina, L V; Zheludkov, M M

2012-01-01

The methods of molecular-genetic differentiation to strain level acquire increasing significance in the current system of struggle with brucellosis. MLVA (multiple locus variable number tandem repeats analysis) was selected for molecular-genetic differentiation to strain level and simultaneous establishment of the genetic relationship of investigated Brucella strains. The goal of this work was MLVA typing of three pathogenic Brucella species strains with the analysis of stability of chosen loci, discrimination power and concordance to conventional phenotypic methods of the Brucella differentiation for use in systematization of brucellosis causing agents. Twenty six Brucella strains representing reference (n = 15), vaccine (n = 2) and field strains of three pathogenic Brucella species were tested: B. melitensis (n = 3), B. abortus (n = 2), B. suis (n = 2), and isolates (n = 2) with unidentified taxonomic position using MLVA with 9 pairs primers on known variable loci of Brucella genome. The analysis of the stability of chosen loci, discrimination power on Hunter-Gaston discrimination index (HGDI) and consistency to phenotypic methods of identification was performed. MLVA was confirmed for the results of phenotypic methods of identification, stability of the chosen loci in majority reference, and vaccine strains with a high index of variability HGDI 0.9969 for all loci. A dendrogram was plotted on the basis of MLVA data on distributed Brucella strains in related clusters according to its taxonomic species and biovar positions and construction of 25 genotypes. B. melitensis strains formed cluster related to the reference strain of B. melitensis 63/9 biovar 2. Australian isolates of Brucella 83-4 and Brucella 83-6 isolated from rodents formed a cluster distant from other strains of Brucella. MLVA is a promising method for differentiation of Brucella strains with known and unresolved taxonomic status for their systematization and creation of MLVA genotype catalogue that will promote qualitative improvement of brucellosis surveillance system in Russia.

[Rubella virus genetic determinant of attenuation].

PubMed

Dmitriev, G V; Borisova, T K; Faizuloev, E B; Desiatskova, R G; Zverev, V V

2014-01-01

Vaccination is the most effective and available way to prevent Rubella. Presently, 9 vaccine strains were registered. Nevertheless, the molecular mechanisms of the attenuation were poorly elucidated for the rubella virus. However, the study of these mechanisms identifying genotypic and phenotypic markers of attenuation, which together with sequence analysis could be used for the genetic stability control of vaccine strains, is still of current interest. Common trends of genetic changes in the process of adaptation to cold were found due to comparison of nucleic acid and amino acid sequences of the Russian strain C-77 with corresponding positions of the known rubella virus strains and its wild type progenitors, if available.

Genetic analyses, phenotypic adaptability and stability in sugarcane genotypes for commercial cultivation in Pernambuco.

PubMed

Dutra Filho, J A; Junior, T C; Simões Neto, D E

2015-10-05

In the present study, we assessed the agro-industrial performance of 22 sugarcane genotypes adaptable to edaphoclimatic conditions in production microregions in the State of Pernambuco, Brazil, and we recommended the commercial cultivation of select genotypes. The variables analyzed were as follows: sucrose percentage in cane juice, tonnage of saccharose per hectare (TPH), sugarcane tonnage per hectare (TCH), fiber, solid soluble contents, total recoverable sugar tonnage (ATR), and total recoverable sugar tonnage per hectare (ATR t/ha). A randomized block design with 4 repeats was used. Combined variance of the experiments, genetic parameter estimates, and environment stratification were analyzed. Phenotypic adaptability and stability were analyzed using the Annicchiarico and Wricke methods and analysis of variance. Genetic gain was estimated using the classic index and sum of ranks. Genotype selection was efficient for TPH, TCH, and ATR t/ha. Genotypes presented a great potential for improvement and a similar response pattern in Litoral Norte and Mata Sul microregions for TPH and TCH and Litoral Norte and Litoral Sul microregions for ATR t/ha. Genotypes SP78-4764, RB813804, and SP79-101 showed better productivity and phenotypic adaptability and stability, according to the Wricke and Annicchiarico methods. These genotypes can be recommended for cultivation in the sugarcane belt in the State of Pernambuco.

Genetic stability and instability of the cis-acting control element of the 5' untranslated region of the poliovirus RNA.

PubMed

Agol, V I

1993-01-01

The poliovirus genome exhibits tremendous plasticity, which is particularly evident when mutations diminishing the growth potential are introduced into the genome. An amazing variability can be observed even among the genomes derived from a single plaque. Not less amazing is the stability of the viral RNA sequences, which could be revealed, for example, upon the analysis of populations of a given viral strain separated by many cycles of reproduction in different laboratories but under standard conditions. This stability is obviously due to very strong selection for the "fit" phenotype. Implications of both the stability and instability of the poliovirus genome for the design, production and use of live poliovirus vaccines are briefly discussed.

Genetic Moderation of Stability in Attachment Security from Early Childhood to Age 18 Years: A Replication Study

ERIC Educational Resources Information Center

Raby, K. Lee; Roisman, Glenn I.; Booth-LaForce, Cathryn

2015-01-01

A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin…

Comprehensive high-resolution genomic profiling and cytogenetics of human chondrocyte cultures by GTG-banding, locus-specific FISH, SKY and SNP array.

PubMed

Wallenborn, M; Petters, O; Rudolf, D; Hantmann, H; Richter, M; Ahnert, P; Rohani, L; Smink, J J; Bulwin, G C; Krupp, W; Schulz, R M; Holland, H

2018-04-23

In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: "In conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies". 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies. Single nucleotide polymorphism (SNP) array analysis was performed on chondrocyte spheroids from five of the six donors. Applying this combination of techniques, the genetic analyses performed revealed no significant genetic instability until passage 3 in monolayer cells and interphase cells from spheroid cultures at different time points. Clonal occurrence of polyploid metaphases and endoreduplications were identified associated with prolonged cultivation time. Also, gonosomal losses were observed in chondrocyte spheroids, with increasing passage and duration of the differentiation phase. Interestingly, in one of the donors, chromosomal aberrations that are also described in extraskeletal myxoid chondrosarcoma were identified. The SNP array analysis exhibited chromosomal aberrations in two donors and copy neutral losses of heterozygosity regions in four donors. This study showed the necessity of combined genetic analyses at defined cultivation time points in quality studies within the field of cell therapy.

Variation in cassava germplasm for tolerance to post-harvest physiological deterioration.

PubMed

Venturini, M T; Santos, L R; Vildoso, C I A; Santos, V S; Oliveira, E J

2016-05-06

Tolerant varieties can effectively control post-harvest physiological deterioration (PPD) of cassava, although knowledge on the genetic variability and inheritance of this trait is needed. The objective of this study was to estimate genetic parameters and identify sources of tolerance to PPD and their stability in cassava accessions. Roots from 418 cassava accessions, grown in four independent experiments, were evaluated for PPD tolerance 0, 2, 5, and 10 days post-harvest. Data were transformed into area under the PPD-progress curve (AUP-PPD) to quantify tolerance. Genetic parameters, stability (Si), adaptability (Ai), and the joint analysis of stability and adaptability (Zi) were obtained via residual maximum likelihood (REML) and best linear unbiased prediction (BLUP) methods. Variance in the genotype (G) x environment (E) interaction and genotypic variance were important for PPD tolerance. Individual broad-sense heritability (hg(2)= 0.38 ± 0.04) and average heritability in accessions (hmg(2)= 0.52) showed high genetic control of PPD tolerance. Genotypic correlation of AUP-PPD in different experiments was of medium magnitude (ȓgA = 0.42), indicating significant G x E interaction. The predicted genotypic values o f G x E free of interaction (û + ĝi) showed high variation. Of the 30 accessions with high Zi, 19 were common to û + ĝi, Si, and Ai parameters. The genetic gain with selection of these 19 cassava accessions was -55.94, -466.86, -397.72, and -444.03% for û + ĝi, Si, Ai, and Zi, respectively, compared with the overall mean for each parameter. These results demonstrate the variability and potential of cassava germplasm to introduce PPD tolerance in commercial varieties.

Cancer heterogeneity: converting a limitation into a source of biologic information.

PubMed

Rübben, Albert; Araujo, Arturo

2017-09-08

Analysis of spatial and temporal genetic heterogeneity in human cancers has revealed that somatic cancer evolution in most cancers is not a simple linear process composed of a few sequential steps of mutation acquisitions and clonal expansions. Parallel evolution has been observed in many early human cancers resulting in genetic heterogeneity as well as multilineage progression. Moreover, aneuploidy as well as structural chromosomal aberrations seems to be acquired in a non-linear, punctuated mode where most aberrations occur at early stages of somatic cancer evolution. At later stages, the cancer genomes seem to get stabilized and acquire only few additional rearrangements. While parallel evolution suggests positive selection of driver mutations at early stages of somatic cancer evolution, stabilization of structural aberrations at later stages suggests that negative selection takes effect when cancer cells progressively lose their tolerance towards additional mutation acquisition. Mixing of genetically heterogeneous subclones in cancer samples reduces sensitivity of mutation detection. Moreover, driver mutations present only in a fraction of cancer cells are more likely to be mistaken for passenger mutations. Therefore, genetic heterogeneity may be considered a limitation negatively affecting detection sensitivity of driver mutations. On the other hand, identification of subclones and subclone lineages in human cancers may lead to a more profound understanding of the selective forces which shape somatic cancer evolution in human cancers. Identification of parallel evolution by analyzing spatial heterogeneity may hint to driver mutations which might represent additional therapeutic targets besides driver mutations present in a monoclonal state. Likewise, stabilization of cancer genomes which can be identified by analyzing temporal genetic heterogeneity might hint to genes and pathways which have become essential for survival of cancer cell lineages at later stages of cancer evolution. These genes and pathways might also constitute patient specific therapeutic targets.

Stability analysis of an autocatalytic protein model

NASA Astrophysics Data System (ADS)

Lee, Julian

2016-05-01

A self-regulatory genetic circuit, where a protein acts as a positive regulator of its own production, is known to be the simplest biological network with a positive feedback loop. Although at least three components—DNA, RNA, and the protein—are required to form such a circuit, stability analysis of the fixed points of this self-regulatory circuit has been performed only after reducing the system to a two-component system, either by assuming a fast equilibration of the DNA component or by removing the RNA component. Here, stability of the fixed points of the three-component positive feedback loop is analyzed by obtaining eigenvalues of the full three-dimensional Hessian matrix. In addition to rigorously identifying the stable fixed points and saddle points, detailed information about the system can be obtained, such as the existence of complex eigenvalues near a fixed point.

Delay decomposition approach to [Formula: see text] filtering analysis of genetic oscillator networks with time-varying delays.

PubMed

Revathi, V M; Balasubramaniam, P

2016-04-01

In this paper, the [Formula: see text] filtering problem is treated for N coupled genetic oscillator networks with time-varying delays and extrinsic molecular noises. Each individual genetic oscillator is a complex dynamical network that represents the genetic oscillations in terms of complicated biological functions with inner or outer couplings denote the biochemical interactions of mRNAs, proteins and other small molecules. Throughout the paper, first, by constructing appropriate delay decomposition dependent Lyapunov-Krasovskii functional combined with reciprocal convex approach, improved delay-dependent sufficient conditions are obtained to ensure the asymptotic stability of the filtering error system with a prescribed [Formula: see text] performance. Second, based on the above analysis, the existence of the designed [Formula: see text] filters are established in terms of linear matrix inequalities with Kronecker product. Finally, numerical examples including a coupled Goodwin oscillator model are inferred to illustrate the effectiveness and less conservatism of the proposed techniques.

Genetic stability of progeny from an artificial allotetraploid carp using sperm from five fish species.

PubMed

Ye, Yuzhen; Wang, Zhongwei; Zhou, Jianfeng; Wu, Qingjiang

2009-08-01

Microsatellite markers and D-loop sequences of mtDNA from a female allotetraploid parent carp and her progenies of generations 1 and 2 induced by sperm of five distant fish species were analyzed. Eleven microsatellite markers were used to identify 48 alleles from the allotetraploid female. The same number of alleles (48) appeared in the first and second generations of the gynogenetic offspring, regardless of the source of the sperm used as an activator. The mtDNA D-loop analysis was performed on the female tetraploid parent, 25 gynogenetic offspring, and 5 sperm-donor species. Fourteen variable sites from the 1,018 bp sequences were observed in the offspring as compared to the female tetraploid parent. Results from D-loop sequence and microsatellite marker analysis showed exclusive maternal transmission, and no genetic information was derived from the father. Our study suggests that progenies of artificial tetraploid carp are genetically stable, which is important for genetic breeding of this tetraploid fish.

RNA isolation from bloodstains collected on FTA cards - application in clinical and forensic genetics.

PubMed

Skonieczna, Katarzyna; Styczyński, Jan; Krenska, Anna; Wysocki, Mariusz; Jakubowska, Aneta; Grzybowski, Tomasz

2016-01-01

Aim of the study: In recent years, RNA analysis has been increasingly used in clinical and forensic genetics. Nevertheless, a major limitation of RNA-based applications is very low RNA stability in biological material, due to the RNAse activity. This highlights the need for improving the methods of RNA collection and storage. Technological approaches such as FTA Classic Cards (Whatman) could provide a solution for the problem of RNA degradation. However, different methods of RNA isolation from FTA cards could have diverse effects on RNA quantity and quality. The purpose of this research was to analyze the utility of three different methods of RNA isolation from peripheral blood collected on FTA Classic Cards (Whatman). The study also aimed at assessing RNA stability in bloodstains deposited on FTA cards. Material and methods: The study was performed on peripheral bloodstains collected from 59 individuals on FTA Classic Cards (Whatman). RNA was isolated with High Pure RNA Isolation Kit (Roche Diagnostics), Universal RNA/miRNA Purification (EURx) and TRIzol Reagent (Life Technologies). RNA was subjected to quantitative analysis followed by reverse transcription and Real - Time PCR reaction. Results: The study has shown that FTA Classic Cards (Whatman) are useful tools for storing bloodstains at room temperature for RNA analysis. Moreover, the method of RNA extraction employing TRIzol Reagent (Life Technologies) provides the highest efficiency and reproducibility for samples stored for no more than 2 years. Conclusions: The FTA cards are suitable for collecting and storing bloodstains for RNA analysis in clinical and forensic genetics.

Spatial extent of analysis influences observed patterns of population genetic structure in a widespread darter species (Percidae)

USGS Publications Warehouse

Argentina, Jane E.; Angermeier, Paul L.; Hallerman, Eric M.; Welsh, Stuart A.

2018-01-01

Connectivity among stream fish populations allows for exchange of genetic material and helps maintain genetic diversity, adaptive potential and population stability over time. Changes in species demographics and population connectivity have the potential to permanently alter the genetic patterns of stream fish, although these changes through space and time are variable and understudied in small‐bodied freshwater fish.As a spatially widespread, common species of benthic freshwater fish, the variegate darter (Etheostoma variatum) is a model species for documenting how patterns of genetic structure and diversity respond to increasing isolation due to large dams and how scale of study may shape our understanding of these patterns. We sampled variegate darters from 34 sites across their range in the North American Ohio River basin and examined how patterns of genetic structure and diversity within and between populations responded to historical population changes and dams within and between populations.Spatial scale and configuration of genetic structure varied across the eight identified populations, from tributaries within a watershed, to a single watershed, to multiple watersheds that encompass Ohio River mainstem habitats. This multiwatershed pattern of population structuring suggests genetic dispersal across large distances was and may continue to be common, although some populations remain isolated despite no apparent structural dispersal barriers. Populations with low effective population sizes and evidence of past population bottlenecks showed low allelic richness, but diversity patterns were not related to watershed size, a surrogate for habitat availability. Pairwise genetic differentiation (FST) increased with fluvial distance and was related to both historic and contemporary processes. Genetic diversity changes were influenced by underlying population size and stability, and while instream barriers were not strong determinants of genetic structuring or loss of genetic diversity, they reduce population connectivity and may impact long‐term population persistence.The broad spatial scale of this study demonstrated the large spatial extent of some variegate darter populations and indicated that dispersal is more extensive than expected given the movement patterns typically observed for small‐bodied, benthic fish. Dam impacts depended on underlying population size and stability, with larger populations more resilient to genetic drift and allelic richness loss than smaller populations.Other darters that inhabit large river habitats may show similar patterns in landscape‐scale studies, and large river barriers may impact populations of small‐bodied fish more than previously expected. Estimation of dispersal rates and behaviours is critical to conservation of imperilled riverine species such as darters.

Trinity: Transcriptome Assembly for Genetic and Functional Analysis of Cancer | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

The cancer transcriptome is shaped by genetic changes, variation in gene transcription, mRNA processing, editing and stability, and the cancer microbiome. Deciphering this variation and understanding its implications on tumorigenesis requires sophisticated computational analyses. Most RNA-Seq analyses rely on methods that first map short reads to a reference genome, and then compare them to annotated transcripts or assemble them. However, this strategy can be limited when the cancer genome is substantially different than the reference or for detecting sequences from the cancer microbiome.

Assessing the relative stabilities of engineered hemoglobins using electrospray mass spectrometry.

PubMed

Apostol, I

1999-07-15

An ion trap mass spectrometer equipped with an electrospray source was used to examine the relative thermodynamic stabilities of various hemoglobins with respect to both tetramer dissociation and hemin dissociation. The results demonstrated that the stability of hemoglobin molecules can be differentiated by the amount of applied collision-induced dissociation (CID) energy necessary to break up the intact tetramer into its constituent globins. The stability of the intact tetramer was affected by single mutations in the beta-globins. The stabilities of the constituent hologlobins were assessed via trap CID of selected ions. The results demonstrated the importance of the contributions of the hologlobin components to the stability of the intact tetramer. Genetic fusion of two alpha-globins, through the introduction of a single glycine residue between the C-terminus of one alpha-chain and the N-terminus of the second, significantly increased the stability of the hemoglobin pseudo-tetramer. Chemical crosslinking of the beta-globins in addition to genetic fusion of alpha-globins further stabilized the hemoglobin molecule. A dihemoglobin molecule produced by the genetic fusion of two di-alpha-globins with a flexible linker demonstrated a decreased stability relative to the corresponding monohemoglobin. Copyright 1999 Academic Press.

Spatio-temporal dynamics of genetic diversity in Sorghum bicolor in Niger.

PubMed

Deu, Monique; Sagnard, F; Chantereau, J; Calatayud, C; Vigouroux, Y; Pham, J L; Mariac, C; Kapran, I; Mamadou, A; Gérard, B; Ndjeunga, J; Bezançon, G

2010-05-01

The dynamics of crop genetic diversity need to be assessed to draw up monitoring and conservation priorities. However, few surveys have been conducted in centres of diversity. Sub-Saharan Africa is the centre of origin of sorghum. Most Sahel countries have been faced with major human, environmental and social changes in recent decades, which are suspected to cause genetic erosion. Sorghum is the second staple cereal in Niger, a centre of diversity for this crop. Niger was submitted to recurrent drought period and to major social changes during these last decades. We report here on a spatio-temporal analysis of sorghum genetic diversity, conducted in 71 villages covering the rainfall gradient and range of agro-ecological conditions in Niger's agricultural areas. We used 28 microsatellite markers and applied spatial and genetic clustering methods to investigate change in genetic diversity over a 26-year period (1976-2003). Global genetic differentiation between the two collections was very low (F (st) = 0.0025). Most of the spatial clusters presented no major differentiation, as measured by F (st), and showed stability or an increase in allelic richness, except for two of them located in eastern Niger. The genetic clusters identified by Bayesian analysis did not show a major change between the two collections in the distribution of accessions between them or in their spatial location. These results suggest that farmers' management has globally preserved sorghum genetic diversity in Niger.

Effects of spaceflight on polysaccharides of Saccharomyces cerevisiae cell wall.

PubMed

Liu, Hong-Zhi; Wang, Qiang; Liu, Xiao-Yong; Tan, Sze-Sze

2008-12-01

Freeze-dried samples of four Saccharomyces cerevisiae strains, namely, FL01, FL03, 2.0016, and 2.1424, were subjected to spaceflight. After the satellite's landing on Earth, the samples were recovered and changes in yeast cell wall were analyzed. Spaceflight strains of all S. cerevisiae strains showed significant changes in cell wall thickness (P < 0.05). One mutant of S. cerevisiae 2.0016 with increased biomass, cell wall thickness, and cell wall glucan was isolated (P < 0.05). The spaceflight mutant of S. cerevisiae 2.0016 showed 46.7%, 62.6%, and 146.0% increment in biomass, cell wall thickness and beta-glucan content, respectively, when compared to the ground strain. Moreover, growth curve analysis showed spaceflight S. cerevisiae 2.0016 had a faster growth rate, shorter lag phase periods, higher final biomass, and higher content of beta-glucan. Genetic stability analysis showed that prolonged subculturing of spaceflight strain S. cerevisiae 2.0016 did not lead to the appearance of variants, indicating that the genetic stability of S. cerevisiae 2.0016 mutant could be sufficient for its exploitation of beta-glucan production.

Etiology of the stability of reading difficulties: the longitudinal twin study of reading disabilities.

PubMed

Astrom, Raven L; Wadsworth, Sally J; DeFries, John C

2007-06-01

Results obtained from previous longitudinal studies of reading difficulties indicate that reading deficits are generally stable. However, little is known about the etiology of this stability. Thus, the primary objective of this first longitudinal twin study of reading difficulties is to provide an initial assessment of genetic and environmental influences on the stability of reading deficits. Data were analyzed from a sample of 56 twin pairs, 18 identical (monozygotic, MZ) and 38 fraternal (dizygotic, DZ), in which at least one member of each pair was classified as reading-disabled in the Colorado Learning Disabilities Research Center, and on whom follow-up data were available. The twins were tested at two time points (average age of 10.3 years at initial assessment and 16.1 years at follow-up). A composite measure of reading performance (PIAT Reading Recognition, Reading Comprehension and Spelling) was highly stable, with a stability correlation of .84. Data from the initial time point were first subjected to univariate DeFries-Fulker multiple regression analysis and the resulting estimate of the heritability of the group deficit (h2g) was .84 (+/-.26). When the initial and follow-up data were then fitted to a bivariate extension of the basic DF model, bivariate heritability was estimated at .65, indicating that common genetic influences account for approximately 75% of the stability between reading measures at the two time points.

Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment

PubMed Central

Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

2015-01-01

Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range. PMID:26138760

Honey bee nest thermoregulation: diversity promotes stability.

PubMed

Jones, Julia C; Myerscough, Mary R; Graham, Sonia; Oldroyd, Benjamin P

2004-07-16

A honey bee colony is characterized by high genetic diversity among its workers, generated by high levels of multiple mating by its queen. Few clear benefits of this genetic diversity are known. Here we show that brood nest temperatures in genetically diverse colonies (i.e., those sired by several males) tend to be more stable than in genetically uniform ones (i.e., those sired by one male). One reason this increased stability arises is because genetically determined diversity in workers' temperature response thresholds modulates the hive-ventilating behavior of individual workers, preventing excessive colony-level responses to temperature fluctuations.

Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure

PubMed Central

Le Nouën, Cyril; McCarty, Thomas; Brown, Michael; Smith, Melissa Laird; Lleras, Roberto; Dolan, Michael A.; Mehedi, Masfique; Yang, Lijuan; Luongo, Cindy; Liang, Bo; Munir, Shirin; DiNapoli, Joshua M.; Mueller, Steffen; Wimmer, Eckard; Collins, Peter L.; Buchholz, Ursula J.

2017-01-01

Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive. During serial passage at progressively increasing temperature, a CPD RSV containing 2,692 synonymous mutations in 9 of 11 ORFs did not lose temperature sensitivity, remained genetically stable, and was restricted at temperatures of 34 °C/35 °C and above. However, a CPD RSV containing 1,378 synonymous mutations solely in the polymerase L ORF quickly lost substantial attenuation. Comprehensive sequence analysis of virus populations identified many different potentially deattenuating mutations in the L ORF as well as, surprisingly, many appearing in other ORFs. Phenotypic analysis revealed that either of two competing mutations in the virus transcription antitermination factor M2-1, outside of the CPD area, substantially reversed defective transcription of the CPD L gene and substantially restored virus fitness in vitro and in case of one of these two mutations, also in vivo. Paradoxically, the introduction into Min L of one mutation each in the M2-1, N, P, and L proteins resulted in a virus with increased attenuation in vivo but increased immunogenicity. Thus, in addition to providing insights on the adaptability of genome-scale deoptimized RNA viruses, stability studies can yield improved synthetic RNA virus vaccine candidates. PMID:28049853

Integrative marker analysis allows risk assessment for metastasis in stage II colon cancer.

PubMed

Nitsche, Ulrich; Rosenberg, Robert; Balmert, Alexander; Schuster, Tibor; Slotta-Huspenina, Julia; Herrmann, Pia; Bader, Franz G; Friess, Helmut; Schlag, Peter M; Stein, Ulrike; Janssen, Klaus-Peter

2012-11-01

Individualized risk assessment in patients with UICC stage II colon cancer based on a panel of molecular genetic alterations. Risk assessment in patients with colon cancer and localized disease (UICC stage II) is not sufficiently reliable. Development of metachronous metastasis is assumed to be governed largely by individual tumor genetics. Fresh frozen tissue from 232 patients (T3-4, N0, M0) with complete tumor resection and a median follow-up of 97 months was analyzed for microsatellite stability, KRAS exon 2, and BRAF exon 15 mutations. Gene expression of the WNT-pathway surrogate marker osteopontin and the metastasis-associated genes SASH1 and MACC1 was determined for 179 patients. The results were correlated with metachronous distant metastasis risk (n = 22 patients). Mutations of KRAS were detected in 30% patients, mutations of BRAF in 15% patients, and microsatellite instability in 26% patients. Risk of recurrence was associated with KRAS mutation (P = 0.033), microsatellite stable tumors (P = 0.015), decreased expression of SASH1 (P = 0.049), and increased expression of MACC1 (P < 0.001). MACC1 was the only independent parameter for recurrence prediction (hazard ratio: 6.2; 95% confidence interval: 2.4-16; P < 0.001). Integrative 2-step cluster analysis allocated patients into 4 groups, according to their tumor genetics. KRAS mutation, BRAF wild type, microsatellite stability, and high MACC1 expression defined the group with the highest risk of recurrence (16%, 7 of 43), whereas BRAF wild type, microsatellite instability, and low MACC1 expression defined the group with the lowest risk (4%, 1 of 26). MACC1 expression predicts development of metastases, outperforming microsatellite stability status, as well as KRAS/BRAF mutation status.

Approximation of state variables for discrete-time stochastic genetic regulatory networks with leakage, distributed, and probabilistic measurement delays: a robust stability problem.

PubMed

Pandiselvi, S; Raja, R; Cao, Jinde; Rajchakit, G; Ahmad, Bashir

2018-01-01

This work predominantly labels the problem of approximation of state variables for discrete-time stochastic genetic regulatory networks with leakage, distributed, and probabilistic measurement delays. Here we design a linear estimator in such a way that the absorption of mRNA and protein can be approximated via known measurement outputs. By utilizing a Lyapunov-Krasovskii functional and some stochastic analysis execution, we obtain the stability formula of the estimation error systems in the structure of linear matrix inequalities under which the estimation error dynamics is robustly exponentially stable. Further, the obtained conditions (in the form of LMIs) can be effortlessly solved by some available software packages. Moreover, the specific expression of the desired estimator is also shown in the main section. Finally, two mathematical illustrative examples are accorded to show the advantage of the proposed conceptual results.

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency

PubMed Central

Lee, Jaewoong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack-Gyun

2017-01-01

Background We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. Methods In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. Results One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. Conclusions The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability. PMID:28028996

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Lee, Jaewoong; Park, Joonhong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack Gyun; Cho, Bin

2017-03-01

We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.

Genetic aspects of autism spectrum disorders: insights from animal models

PubMed Central

Banerjee, Swati; Riordan, Maeveen; Bhat, Manzoor A.

2014-01-01

Autism spectrum disorders (ASDs) are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development, and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy, and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute toward the formation, stabilization, and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD. PMID:24605088

ASSESSMENT OF MOLECULAR GENETIC STABILITY BETWEEN LONG-TERM CRYOPRESERVED AND TISSUE CULTURED WASABI (Wasabia japonica) PLANTS.

PubMed

Maki, S; Hirai, Y; Niino, T; Matsumoto, T

2015-01-01

Maintaining the genetic integrity in long-term tissue cultured and cryopreserved plants is important for the conservation of plant genetic resources. In this study, the genetic stability of cryopreserved wasabi shoot tips stored for 10 years at -150 degree C was visualized using Amplified Fragment Length Polymorphism (AFLP) and Methylation Sensitive Amplified Polymorphism (MSAP). The study included plants derived from cryopreserved shoot tips after 10.5 years storage at -150 degree C (LN10yr), after 2 h storage at -196 degree C (LN2hr), cryopreservation controls (No LN cooling (TC)) and non-treated controls without LN cooling (LC). The donor plants for LN2hr, TC and LC were also maintained in vitro at 20 degree C for the same period. Neither technique detected genetic variations in either control or cryopreserved plants. Some mutations were noted in plants maintained in tissue culture for 10 years. Comparison of genome stability for TC and LN2hr plants showed only a minor change in DNA. However, when comparing the LC and Ln10yr, many differences were found. We conclude that cryopreservation is a superior conservation method compared to tissue culture in maintaining genetic stability for a long-term storage of wasabi germplasm.

Genetic stability and phytochemical analysis of the in vitro regenerated plants of Dendrobium nobile Lindl., an endangered medicinal orchid

PubMed Central

Bhattacharyya, Paromik; Kumaria, Suman; Diengdoh, Reemavareen; Tandon, Pramod

2014-01-01

An efficient genetically stable regeneration protocol with increased phytochemical production has been established for Dendrobium nobile, a highly prized orchid for its economic and medicinal importance. Protocorm like bodies (PLBs) were induced from the pseudostem segments using thidiazuron (TDZ; 1.5 mg/l), by-passing the conventional auxin–cytokinin complement approach for plant regeneration. Although, PLB induction was observed at higher concentrations of TDZ, plantlet regeneration from those PLBs was affected adversely. The best rooting (5.41 roots/shoot) was achieved in MS medium with 1.5 mg/l TDZ and 0.25% activated charcoal. Plantlets were successfully transferred to a greenhouse with a survival rate of 84.3%, exhibiting normal development. Genetic stability of the regenerated plants was investigated using randomly amplified polymorphic DNA (RAPD) and start codon targeted (SCoT) polymorphism markers which detected 97% of genetic fidelity among the regenerants. The PIC values of RAPD and SCoT primers were recorded to be 0.92 and 0.76 and their Rp values ranged between 3.66 and 10, and 4 and 12 respectively. The amplification products of the regenerated plants showed similar banding patterns to that of the mother plant thus demonstrating the homogeneity of the micropropagated plants. A comparative phytochemical analysis among the mother and the micropropagated plants showed a higher yield of secondary metabolites. The regeneration protocol developed in this study provides a basis for ex-situ germplasm conservation and also harnesses the various secondary metabolite compounds of medicinal importance present in D. nobile. PMID:25606433

Genetic moderation of stability in attachment security from early childhood to age 18 years: A replication study.

PubMed

Raby, K Lee; Roisman, Glenn I; Booth-LaForce, Cathryn

2015-11-01

A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin receptor (OXTR) genetic variants. Using longitudinal data from over 550 individuals, there was no evidence that OXTR rs53576 moderated the association between attachment security during early childhood and overall coherence of mind ("security") during the Adult Attachment Interview at age 18 years. Additional analyses involving a second commonly investigated OXTR variant (rs2254298) and indices of individuals' dismissing and preoccupied attachment states of mind also failed to provide robust evidence for oxytonergic moderation of the stability in attachment security across development. The discussion focuses on research strategies for investigating genetic contributions to attachment security across the life span. (c) 2015 APA, all rights reserved).

Moderation of Harsh Parenting on Genetic and Environmental Contributions to Child and Adolescent Deviant Peer Affiliation: A Longitudinal Twin Study.

PubMed

Li, Mengjiao; Chen, Jie; Li, Xinying; Deater-Deckard, Kirby

2015-07-01

Affiliation with deviant peers is associated with biologically influenced personal attributes, and is itself a major contributor to growth in antisocial behavior over childhood and adolescence. Several studies have shown that variance in child and adolescent deviant peer affiliation includes genetic and non-genetic influences, but none have examined longitudinal genetic and environmental stability or change within the context of harsh parenting. To address this gap, we tested the moderating role of harsh parenting on genetic and environmental stability or change of deviant peer affiliation in a longitudinal (spanning one and a half years) study of Chinese child and adolescent twin pairs (N = 993, 52.0% female). Using multiple informants (child- and parent-reports) and measurement methods to minimize rater bias, we found that individual differences in deviant peer affiliation at each assessment were similarly explained by moderate genetic and nonshared environmental variance. The longitudinal stability and change of deviant peer affiliation were explained by genetic and nonshared environmental factors. The results also revealed that the genetic variance for deviant peer affiliation is higher in the families with harsher parenting. This amplified genetic risk underscores the role of harsh parenting in the selection and socialization process of deviant peer relationships.

Pleiotropic Models of Polygenic Variation, Stabilizing Selection, and Epistasis

PubMed Central

Gavrilets, S.; de-Jong, G.

1993-01-01

We show that in polymorphic populations many polygenic traits pleiotropically related to fitness are expected to be under apparent ``stabilizing selection'' independently of the real selection acting on the population. This occurs, for example, if the genetic system is at a stable polymorphic equilibrium determined by selection and the nonadditive contributions of the loci to the trait value either are absent, or are random and independent of those to fitness. Stabilizing selection is also observed if the polygenic system is at an equilibrium determined by a balance between selection and mutation (or migration) when both additive and nonadditive contributions of the loci to the trait value are random and independent of those to fitness. We also compare different viability models that can maintain genetic variability at many loci with respect to their ability to account for the strong stabilizing selection on an additive trait. Let V(m) be the genetic variance supplied by mutation (or migration) each generation, V(g) be the genotypic variance maintained in the population, and n be the number of the loci influencing fitness. We demonstrate that in mutation (migration)-selection balance models the strength of apparent stabilizing selection is order V(m)/V(g). In the overdominant model and in the symmetric viability model the strength of apparent stabilizing selection is approximately 1/(2n) that of total selection on the whole phenotype. We show that a selection system that involves pairwise additive by additive epistasis in maintaining variability can lead to a lower genetic load and genetic variance in fitness (approximately 1/(2n) times) than an equivalent selection system that involves overdominance. We show that, in the epistatic model, the apparent stabilizing selection on an additive trait can be as strong as the total selection on the whole phenotype. PMID:8325491

Genetic analysis of some agronomic and fiber traits in Gossypium hirsutum L. grown in field conditions

USDA-ARS?s Scientific Manuscript database

Cotton production is an essential component of the economy of Pakistan, and continuing to improve the yield and fiber quality of this crop will ensure the future stability of this industry. Combining ability describes the performance of genotypes when they are crossed together, and it is a common me...

SES and CHAOS as Environmental Mediators of Cognitive Ability: A Longitudinal Genetic Analysis

ERIC Educational Resources Information Center

Hart, Sara A.; Petrill, Stephen A.; Deckard, Kirby Deater; Thompson, Lee A.

2007-01-01

This study examined shared environmental influences on the longitudinal stability of general cognitive ability, as mediated by socioeconomic status and chaos in the home, using 287 pairs of elementary school-age twins drawn from the Western Reserve Reading Project (WRRP). General cognitive ability was evaluated at two annual assessments using the…

Crop Genetics: The Seeds of Revolution.

ERIC Educational Resources Information Center

DeYoung, H. Garrett

1983-01-01

Current research in plant genetics is described. Benefits of this research (which includes genetic engineering applications) will include reduction/elimination of crop diseases, assurance of genetic stability, and the creation of new crop varieties. (JN)

Global optimization of small bimetallic Pd-Co binary nanoalloy clusters: a genetic algorithm approach at the DFT level.

PubMed

Aslan, Mikail; Davis, Jack B A; Johnston, Roy L

2016-03-07

The global optimisation of small bimetallic PdCo binary nanoalloys are systematically investigated using the Birmingham Cluster Genetic Algorithm (BCGA). The effect of size and composition on the structures, stability, magnetic and electronic properties including the binding energies, second finite difference energies and mixing energies of Pd-Co binary nanoalloys are discussed. A detailed analysis of Pd-Co structural motifs and segregation effects is also presented. The maximal mixing energy corresponds to Pd atom compositions for which the number of mixed Pd-Co bonds is maximised. Global minimum clusters are distinguished from transition states by vibrational frequency analysis. HOMO-LUMO gap, electric dipole moment and vibrational frequency analyses are made to enable correlation with future experiments.

Tracking the Genetic Stability of a Honey Bee (Hymenoptera: Apidae) Breeding Program With Genetic Markers.

PubMed

Bourgeois, Lelania; Beaman, Lorraine

2017-08-01

A genetic stock identification (GSI) assay was developed in 2008 to distinguish Russian honey bees from other honey bee stocks that are commercially produced in the United States. Probability of assignment (POA) values have been collected and maintained since the stock release in 2008 to the Russian Honey Bee Breeders Association. These data were used to assess stability of the breeding program and the diversity levels of the contemporary breeding stock through comparison of POA values and genetic diversity parameters from the initial release to current values. POA values fluctuated throughout 2010-2016, but have recovered to statistically similar levels in 2016 (POA(2010) = 0.82, POA(2016) = 0.74; P = 0.33). Genetic diversity parameters (i.e., allelic richness and gene diversity) in 2016 also remained at similar levels when compared to those in 2010. Estimates of genetic structure revealed stability (FST(2009/2016) = 0.0058) with a small increase in the estimate of the inbreeding coefficient (FIS(2010) = 0.078, FIS(2016) = 0.149). The relationship among breeding lines, based on genetic distance measurement, was similar in 2008 and 2016 populations, but with increased homogeneity among lines (i.e., decreased genetic distance). This was expected based on the closed breeding system used for Russian honey bees. The successful application of the GSI assay in a commercial breeding program demonstrates the utility and stability of such technology to contribute to and monitor the genetic integrity of a breeding stock of an insect species. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

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

PubMed Central

Zhang, Xu-Sheng; Hill, William G

2002-01-01

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

Comparing the Developmental Genetics of Cognition and Personality over the Life Span.

PubMed

Briley, Daniel A; Tucker-Drob, Elliot M

2017-02-01

Empirical studies of cognitive ability and personality have tended to operate in isolation of one another. We suggest that returning to a unified approach to considering the development of individual differences in both cognition and personality can enrich our understanding of human development. We draw on previous meta-analyses of longitudinal, behavior genetic studies of cognition and personality across the life span, focusing particular attention on age trends in heritability and differential stability. Both cognition and personality are moderately heritable and exhibit large increases in stability with age; however, marked differences are evident. First, the heritability of cognition increases substantially with child age, while the heritability of personality decreases modestly with age. Second, increasing stability of cognition with age is overwhelmingly mediated by genetic factors, whereas increasing stability of personality with age is entirely mediated by environmental factors. Third, the maturational time-course of stability differs: Stability of cognition nears its asymptote by the end of the first decade of life, whereas stability of personality takes three decades to near its asymptote. We discuss how proximal gene-environment dynamics, developmental processes, broad social contexts, and evolutionary pressures may intersect to give rise to these divergent patterns. © 2015 Wiley Periodicals, Inc.

Comparing the Developmental Genetics of Cognition and Personality over the Lifespan

PubMed Central

Briley, Daniel A.; Tucker-Drob, Elliot M.

2015-01-01

Objective Empirical studies of cognitive ability and personality have tended to operate in isolation of one another. We suggest that returning to a unified approach to considering the development of individual differences in both cognition and personality can enrich our understanding of human development. Method We draw on previous meta-analyses of longitudinal, behavior genetic studies of cognition and personality across the lifespan, focusing particular attention on age trends in heritability and differential stability. Results Both cognition and personality are moderately heritable and exhibit large increases in stability with age; however, marked differences are evident. First, the heritability of cognition increases substantially with child age, while the heritability of personality decreases modestly with age. Second, increasing stability of cognition with age is overwhelmingly mediated by genetic factors, whereas increasing stability of personality with age is entirely mediated by environmental factors. Third, the maturational time-course of stability differs: Stability of cognition nears its asymptote by the end of the first decade of life, whereas stability of personality takes three decades to near its asymptote. Conclusions We discuss how proximal gene-environment dynamics, developmental processes, broad social contexts, and evolutionary pressures may intersect to give rise to these divergent patterns. PMID:26045299

Spatial and Temporal Dynamics of Pacific Oyster Hemolymph Microbiota across Multiple Scales

PubMed Central

Lokmer, Ana; Goedknegt, M. Anouk; Thieltges, David W.; Fiorentino, Dario; Kuenzel, Sven; Baines, John F.; Wegner, K. Mathias

2016-01-01

Unveiling the factors and processes that shape the dynamics of host associated microbial communities (microbiota) under natural conditions is an important part of understanding and predicting an organism's response to a changing environment. The microbiota is shaped by host (i.e., genetic) factors as well as by the biotic and abiotic environment. Studying natural variation of microbial community composition in multiple host genetic backgrounds across spatial as well as temporal scales represents a means to untangle this complex interplay. Here, we combined a spatially-stratified with a longitudinal sampling scheme within differentiated host genetic backgrounds by reciprocally transplanting Pacific oysters between two sites in the Wadden Sea (Sylt and Texel). To further differentiate contingent site from host genetic effects, we repeatedly sampled the same individuals over a summer season to examine structure, diversity and dynamics of individual hemolymph microbiota following experimental removal of resident microbiota by antibiotic treatment. While a large proportion of microbiome variation could be attributed to immediate environmental conditions, we observed persistent effects of antibiotic treatment and translocation suggesting that hemolymph microbial community dynamics is subject to within-microbiome interactions and host population specific factors. In addition, the analysis of spatial variation revealed that the within-site microenvironmental heterogeneity resulted in high small-scale variability, as opposed to large-scale (between-site) stability. Similarly, considerable within-individual temporal variability was in contrast with the overall temporal stability at the site level. Overall, our longitudinal, spatially-stratified sampling design revealed that variation in hemolymph microbiota is strongly influenced by site and immediate environmental conditions, whereas internal microbiome dynamics and oyster-related factors add to their long-term stability. The combination of small and large scale resolution of spatial and temporal observations therefore represents a crucial but underused tool to study host-associated microbiome dynamics. PMID:27630625

Conformation and Stability of Intramolecular Telomeric G-Quadruplexes: Sequence Effects in the Loops

PubMed Central

Sattin, Giovanna; Artese, Anna; Nadai, Matteo; Costa, Giosuè; Parrotta, Lucia; Alcaro, Stefano; Palumbo, Manlio; Richter, Sara N.

2013-01-01

Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation restricted to loop bases, indicating that the variant telomeric sequences maintain the ability to fold into G-quadruplex. To assess the effect of mutations in loop bases on G-quadruplex folding and stability, we performed a comprehensive analysis of mutant telomeric sequences by spectroscopic techniques, molecular dynamics simulations and gel electrophoresis. We found that when the first position in the loop was mutated from T to C or A the resulting structure adopted a less stable antiparallel topology; when the second position was mutated to C or A, lower thermal stability and no evident conformational change were observed; in contrast, substitution of the third position from A to C induced a more stable and original hybrid conformation, while mutation to T did not significantly affect G-quadruplex topology and stability. Our results indicate that allelic variations generate G-quadruplex telomeric structures with variable conformation and stability. This aspect needs to be taken into account when designing new potential anticancer molecules. PMID:24367632

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view. PMID:23515240

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

Cortisol reactivity to stress among youth: Stability over time and genetic variants for stress sensitivity

PubMed Central

Hankin, Benjamin L.; Badanes, Lisa S.; Smolen, Andrew; Young, Jami F.

2015-01-01

Stress sensitivity may be one process that can explain why some genetically at-risk individuals are more susceptible to some types of stress-reactive psychopathologies. Dysregulation of the Limbic Hypothalamic Pituitary Adrenal (LHPA) axis, including cortisol reactivity to challenge, represents a key aspect of stress sensitivity. However, the degree of stability over time among youth, especially differential stability as a function of particular genetic variants, has not been investigated. A general community sample of children and adolescents (mean age = 11.4; 56% girls) provided a DNA sample and completed two separate laboratory stress challenges, across an 18-month follow-up (N =224 at Time 1; N = 194 at Time 2), with repeated measures of salivary cortisol. Results showed that test-retest stability for several indices of cortisol reactivity across the laboratory challenge visits were significant and of moderate magnitude for the whole sample. Moreover, gene variants of several biologically plausible systems relevant for stress sensitivity (especially 5-HTTLPR and CRHR1) demonstrated differential stability of cortisol reactivity over 18-months, such that carriers of genotypes conferring enhanced environmental susceptibility exhibited greater stability of cortisol levels over time for some LHPA axis indices. Findings suggest that LHPA axis dysregulation may exhibit some trait-like aspects underlying stress sensitivity in youth, especially for those who carry genes related to greater genetic susceptibility to environmental stress. PMID:25688432

Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation

PubMed Central

Porto, Arthur; Sebastião, Harley; Pavan, Silvia Eliza; VandeBerg, John L.; Marroig, Gabriel; Cheverud, James M.

2015-01-01

We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyze the morphological diversification of the Monodelphis brevicaudata species group. We found that within-species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between-species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation. PMID:25818173

Longevity of clonal plants: why it matters and how to measure it

PubMed Central

de Witte, Lucienne C.; Stöcklin, Jürg

2010-01-01

Background Species' life-history and population dynamics are strongly shaped by the longevity of individuals, but life span is one of the least accessible demographic traits, particularly in clonal plants. Continuous vegetative reproduction of genets enables persistence despite low or no sexual reproduction, affecting genet turnover rates and population stability. Therefore, the longevity of clonal plants is of considerable biological interest, but remains relatively poorly known. Scope Here, we critically review the present knowledge on the longevity of clonal plants and discuss its importance for population persistence. Direct life-span measurements such as growth-ring analysis in woody plants are relatively easy to take, although, for many clonal plants, these methods are not adequate due to the variable growth pattern of ramets and difficult genet identification. Recently, indirect methods have been introduced in which genet size and annual shoot increments are used to estimate genet age. These methods, often based on molecular techniques, allow the investigation of genet size and age structure of whole populations, a crucial issue for understanding their viability and persistence. However, indirect estimates of clonal longevity are impeded because the process of ageing in clonal plants is still poorly understood and because their size and age are not always well correlated. Alternative estimators for genet life span such as somatic mutations have recently been suggested. Conclusions Empirical knowledge on the longevity of clonal species has increased considerably in the last few years. Maximum age estimates are an indicator of population persistence, but are not sufficient to evaluate turnover rates and the ability of long-lived clonal plants to enhance community stability and ecosystem resilience. In order to understand the dynamics of populations it will be necessary to measure genet size and age structure, not only life spans of single individuals, and to use such data for modelling of genet dynamics. PMID:20880935

Dynamical Analysis of Density-dependent Selection in a Discrete one-island Migration Model

Treesearch

James H. Roberds; James F. Selgrade

2000-01-01

A system of non-linear difference equations is used to model the effects of density-dependent selection and migration in a population characterized by two alleles at a single gene locus. Results for the existence and stability of polymorphic equilibria are established. Properties for a genetically important class of equilibria associated with complete dominance in...

Longitudinal Stability in Reading Comprehension Is Largely Heritable from Grades 1 to 6

PubMed Central

Soden, Brooke; Christopher, Micaela E.; Hulslander, Jacqueline; Olson, Richard K.; Cutting, Laurie; Keenan, Janice M.; Thompson, Lee A.; Wadsworth, Sally J.; Willcutt, Erik G.; Petrill, Stephen A.

2015-01-01

Reading comprehension is a foundational academic skill and significant attention has focused on reading development. This report is the first to examine the stability and change in genetic and environmental influences on reading comprehension across Grades 1 to 6. This developmental range is particularly important because it encompasses the timespan in which most children move from learning how to read to using reading for learning. Longitudinal simplex models were fitted separately for two independent twin samples (N = 706; N = 976). Results suggested that the shared environment contributed to variance in early but not later reading. Instead, stability in reading development was largely mediated by continuous genetic influences. Thus, although reading is clearly a learned skill and the environment remains important for reading development, individual differences in reading comprehension appear to be also influenced by a core of genetic stability that persists through the developmental course of reading. PMID:25602760

A selfish genetic element confers non-Mendelian inheritance in rice.

PubMed

Yu, Xiaowen; Zhao, Zhigang; Zheng, Xiaoming; Zhou, Jiawu; Kong, Weiyi; Wang, Peiran; Bai, Wenting; Zheng, Hai; Zhang, Huan; Li, Jing; Liu, Jiafan; Wang, Qiming; Zhang, Long; Liu, Kai; Yu, Yang; Guo, Xiuping; Wang, Jiulin; Lin, Qibing; Wu, Fuqing; Ren, Yulong; Zhu, Shanshan; Zhang, Xin; Cheng, Zhijun; Lei, Cailin; Liu, Shijia; Liu, Xi; Tian, Yunlu; Jiang, Ling; Ge, Song; Wu, Chuanyin; Tao, Dayun; Wang, Haiyang; Wan, Jianmin

2018-06-08

Selfish genetic elements are pervasive in eukaryote genomes, but their role remains controversial. We show that qHMS7 , a major quantitative genetic locus for hybrid male sterility between wild rice ( Oryza meridionalis ) and Asian cultivated rice ( O. sativa ), contains two tightly linked genes [ Open Reading Frame 2 ( ORF2 ) and ORF3 ]. ORF2 encodes a toxic genetic element that aborts pollen in a sporophytic manner, whereas ORF3 encodes an antidote that protects pollen in a gametophytic manner. Pollens lacking ORF3 are selectively eliminated, leading to segregation distortion in the progeny. Analysis of the genetic sequence suggests that ORF3 arose first, followed by gradual functionalization of ORF2 Furthermore, this toxin-antidote system may have promoted the differentiation and/or maintained the genome stability of wild and cultivated rice. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Joint Identification of Genetic Variants for Physical Activity in Korean Population

PubMed Central

Kim, Jayoun; Kim, Jaehee; Min, Haesook; Oh, Sohee; Kim, Yeonjung; Lee, Andy H.; Park, Taesung

2014-01-01

There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY) was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA. PMID:25026172

Production and Characterization of Chemically Inactivated Genetically Engineered Clostridium difficile Toxoids.

PubMed

Vidunas, Eugene; Mathews, Antony; Weaver, Michele; Cai, Ping; Koh, Eun Hee; Patel-Brown, Sujata; Yuan, Hailey; Zheng, Zi-Rong; Carriere, Marjolaine; Johnson, J Erik; Lotvin, Jason; Moran, Justin

2016-07-01

A recombinant Clostridium difficile expression system was used to produce genetically engineered toxoids A and B as immunogens for a prophylactic vaccine against C. difficile-associated disease. Although all known enzymatic activities responsible for cytotoxicity were genetically abrogated, the toxoids exhibited residual cytotoxic activity as measured in an in vitro cell-based cytotoxicity assay. The residual cytotoxicity was eliminated by treating the toxoids with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide. Mass spectrometry and amino acid analysis of the EDC-inactivated toxoids identified crosslinks, glycine adducts, and β-alanine adducts. Surface plasmon resonance analysis demonstrated that modifications resulting from the chemical treatment did not appreciably affect recognition of epitopes by both toxin A- and B-specific neutralizing monoclonal antibodies. Compared to formaldehyde-inactivated toxoids, the EDC/N-hydroxysuccinimide-inactivated toxoids exhibited superior stability in solution with respect to reversion of cytotoxic activity. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Nonselective enrichment for yeast adenine mutants by flow cytometry

NASA Technical Reports Server (NTRS)

Bruschi, C. V.; Chuba, P. J.

1988-01-01

The expression of certain adenine biosynthetic mutations in the yeast Saccharomyces cerevisiae results in a red colony color. This phenomenon has historically provided an ideal genetic marker for the study of mutation, recombination, and aneuploidy in lower eukaryotes by classical genetic analysis. In this paper, it is reported that cells carrying ade1 and/or ade2 mutations exhibit primary fluorescence. Based on this observation, the nonselective enrichment of yeast cultures for viable adenine mutants by using the fluorescence-activated cell sorter has been achieved. The advantages of this approach over conventional genetic analysis of mutation, recombination, and mitotic chromosomal stability include speed and accuracy in acquiring data for large numbers of clones. By using appropriate strains, the cell sorter has been used for the isolation of both forward mutations and chromosomal loss events in S. cerevisiae. The resolving power of this system and its noninvasiveness can easily be extended to more complex organisms, including mammalian cells, in which analogous metabolic mutants are available.

40 CFR 158.2170 - Experimental use permit data requirements-microbial pesticides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements for genetically modified microbial pesticides may include but are not limited to: genetic... genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

40 CFR 158.2170 - Experimental use permit data requirements-microbial pesticides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirements for genetically modified microbial pesticides may include but are not limited to: genetic... genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

40 CFR 158.2170 - Experimental use permit data requirements-microbial pesticides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... requirements for genetically modified microbial pesticides may include but are not limited to: genetic... genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

40 CFR 158.2170 - Experimental use permit data requirements-microbial pesticides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... requirements for genetically modified microbial pesticides may include but are not limited to: genetic... genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

Analysis on the DNA Fingerprinting of Aspergillus Oryzae Mutant Induced by High Hydrostatic Pressure

NASA Astrophysics Data System (ADS)

Wang, Hua; Zhang, Jian; Yang, Fan; Wang, Kai; Shen, Si-Le; Liu, Bing-Bing; Zou, Bo; Zou, Guang-Tian

2011-01-01

The mutant strains of aspergillus oryzae (HP300a) are screened under 300 MPa for 20 min. Compared with the control strains, the screened mutant strains have unique properties such as genetic stability, rapid growth, lots of spores, and high protease activity. Random amplified polymorphic DNA (RAPD) and inter simple sequence repeats (ISSR) are used to analyze the DNA fingerprinting of HP300a and the control strains. There are 67.9% and 51.3% polymorphic bands obtained by these two markers, respectively, indicating significant genetic variations between HP300a and the control strains. In addition, comparison of HP300a and the control strains, the genetic distances of random sequence and simple sequence repeat of DNA are 0.51 and 0.34, respectively.

Genetic and Environmental Stability in Attention Problems across the Lifespan: Evidence from the Netherlands Twin Register

ERIC Educational Resources Information Center

Kan, Kees-Jan; Dolan, Conor V.; Nivard, Michel G.; Middeldorp, Christel M.; van Beijsterveldt, Catharina E. M.; Willemsen, Gonneke; Boomsma, Dorret I.

2013-01-01

Objective: To review findings on attention-deficit/hyperactivity disorder and attention problems (AP) in children, adolescents, and adults, as established in the database of the Netherlands Twin Register and increase the understanding of stability in AP across the lifespan as a function of genetic and environmental influences. Method: A…

Genetic variation, phenotypic stability, and repeatability of drought response in European larch throughout 50 years in a common garden experiment

PubMed Central

George, Jan-Peter; Grabner, Michael; Karanitsch-Ackerl, Sandra; Mayer, Konrad; Weißenbacher, Lambert; Schueler, Silvio

2017-01-01

Abstract Assessing intra-specific variation in drought stress response is required to mitigate the consequences of climate change on forest ecosystems. Previous studies suggest that European larch (Larix decidua Mill.), an important European conifer in mountainous and alpine forests, is highly vulnerable to drought. In light of this, we estimated the genetic variation in drought sensitivity and its degree of genetic determination in a 50-year-old common garden experiment in the drought-prone northeastern Austria. Tree ring data from larch provenances originating from across the species' natural range were used to estimate the drought reaction in four consecutive drought events (1977, 1981, 1990–1994, and 2003) with extremely low standardized precipitation- and evapotranspiration-index values that affected growth in all provenances. We found significant differences among provenances across the four drought periods for the trees’ capacity to withstand drought (resistance) and for their capacity to reach pre-drought growth levels after drought (resilience). Provenances from the species' northern distribution limit in the Polish lowlands were found to be more drought resistant and showed higher stability across all drought periods than provenances from mountainous habitats at the southern fringe. The degree of genetic determination, as estimated by the repeatability, ranged up to 0.39, but significantly differed among provenances, indicating varying degrees of natural selection at the provenance origin. Generally, the relationship between the provenances’ source climate and drought behavior was weak, suggesting that the contrasting patterns of drought response are a result of both genetic divergence out of different refugial lineages and local adaptation to summer or winter drought conditions. Our analysis suggests that European larch posseses high genetic variation among and within provenances that can be used for assisted migration and breeding programs. PMID:28173601

Difficult temperament and negative parenting in early childhood: a genetically informed cross-lagged analysis

PubMed Central

Micalizzi, Lauren; Wang, Manjie; Saudino, Kimberly J.

2015-01-01

A genetically informed longitudinal cross-lagged model was applied to twin data to explore etiological links between difficult temperament and negative parenting in early childhood. The sample comprised 313 monozygotic (MZ) and dizygotic (DZ) twin pairs. Difficult temperament and negative parenting were assessed at ages 2 and 3 using parent ratings. Both constructs were interrelated within and across age (rs .34–.47) and showed substantial stability (rs .65–.68). Difficult temperament and negative parenting were influenced by genetic and environmental factors at ages 2 and 3. The genetic and nonshared environmental correlations (rs .21–.76) at both ages suggest overlap at the level of etiology between the phenotypes. Significant bidirectional associations between difficult temperament and negative parenting were found. The cross-lagged association from difficult temperament at age 2 to negative parenting at age 3 and from negative parenting at age 2 and difficult temperament at age 3 were due to genetic, shared environmental, and nonshared environmental factors. Substantial novel genetic and nonshared environmental influences emerged at age 3 and suggest change in the etiology of these constructs over time. PMID:26490166

Live Respiratory Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized Temperature-Sensitivity Mutations Is Highly Attenuated in RSV-Seronegative Infants and Children.

PubMed

Buchholz, Ursula J; Cunningham, Coleen K; Muresan, Petronella; Gnanashanmugam, Devasena; Sato, Paul; Siberry, George K; Rexroad, Vivian; Valentine, Megan; Perlowski, Charlotte; Schappell, Elizabeth; Thumar, Bhagvinji; Luongo, Cindy; Barr, Emily; Aziz, Mariam; Yogev, Ram; Spector, Stephen A; Collins, Peter L; McFarland, Elizabeth J; Karron, Ruth A

2018-04-11

Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation. RSV-seronegative 6-24-month-old children received an intranasal dose of 105.3 plaque-forming units (PFU) of RSVcps2 (n = 34) or placebo (n = 16) (International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1114 and companion protocol CIR285). RSV serum neutralizing antibody titers before and 56 days after vaccination, vaccine virus infectivity (defined as vaccine virus shedding detectable in nasal wash and/or a ≥4-fold rise in serum antibodies), reactogenicity, and genetic stability were assessed. During the following RSV transmission season, participants were monitored for respiratory illness, with serum antibody titers measured before and after the season. A total of 85% of vaccinees were infected with RSVcps2 (median peak titer, 0.5 log10 PFU/mL by culture and 2.9 log10 copies/mL by polymerase chain reaction analysis); 77% shed vaccine virus, and 59% developed a ≥4-fold rise in RSV-serum neutralizing antibody titers. Respiratory tract and/or febrile illness occurred at the same rate (50%) in the vaccine and placebo groups. Deattenuation was not detected at either of 2 stabilized mutation sites. RSVcps2 was well tolerated and moderately immunogenic and had increased genetic stability in 6-24-month-old RSV-seronegative children. NCT01852266 and NCT01968083.

Stability and morphological and molecular-genetic identification of algae in buried soils

NASA Astrophysics Data System (ADS)

Temraleeva, A. D.; Moskalenko, S. V.; El'tsov, M. V.; Vagapov, I. M.; Ovchinnikov, A. Yu.; Gugalinskaya, L. A.; Alifanov, V. M.; Pinskii, D. L.

2017-08-01

Living cultural strains of the green algae `Chlorella' mirabilis and Muriella terrestris have been isolated from buried soils, and their identification has been confirmed by morphological and molecular-genetic analysis. It has been shown that the retention of their viability could be related to their small size and the presence of sporopollenin in cell walls. The effect of methods for the reactivation of dormant microbial forms on the growth of algae in paleosols has been estimated. The total DNA content has been determined in buried and recent background soils, and relationship between DNA and the presence and age of burial has been established.

The Effects of Predator Evolution and Genetic Variation on Predator-Prey Population-Level Dynamics.

PubMed

Cortez, Michael H; Patel, Swati

2017-07-01

This paper explores how predator evolution and the magnitude of predator genetic variation alter the population-level dynamics of predator-prey systems. We do this by analyzing a general eco-evolutionary predator-prey model using four methods: Method 1 identifies how eco-evolutionary feedbacks alter system stability in the fast and slow evolution limits; Method 2 identifies how the amount of standing predator genetic variation alters system stability; Method 3 identifies how the phase lags in predator-prey cycles depend on the amount of genetic variation; and Method 4 determines conditions for different cycle shapes in the fast and slow evolution limits using geometric singular perturbation theory. With these four methods, we identify the conditions under which predator evolution alters system stability and shapes of predator-prey cycles, and how those effect depend on the amount of genetic variation in the predator population. We discuss the advantages and disadvantages of each method and the relations between the four methods. This work shows how the four methods can be used in tandem to make general predictions about eco-evolutionary dynamics and feedbacks.

The A-Like Faker Assay for Measuring Yeast Chromosome III Stability.

PubMed

Novoa, Carolina A; Ang, J Sidney; Stirling, Peter C

2018-01-01

The ability to rapidly assess chromosome instability (CIN) has enabled profiling of most yeast genes for potential effects on genome stability. The A-like faker (ALF) assay is one of several qualitative and quantitative marker loss assays that indirectly measure loss or conversion of genetic material using a counterselection step. The ALF assay relies on the ability to count spurious mating events that occur upon loss of the MATα locus of haploid Saccharomyces cerevisiae strains. Here, we describe the deployment of the ALF assay for both rapid and simple qualitative, and more in-depth quantitative analysis allowing determination of absolute ALF frequencies.

Genetic stability of Brucella abortus isolates from an outbreak by multiple-locus variable-number tandem repeat analysis (MLVA16)

PubMed Central

2014-01-01

Background Brucellosis caused by Brucella abortus is one of the most important zoonoses in the world. Multiple-locus variable-number tandem repeat analysis (MLVA16) has been shown be a useful tool to epidemiological traceback studies in B. abortus infection. Thus, the present study aimed (i) to evaluate the genetic diversity of B. abortus isolates from a brucellosis outbreak, and (ii) to investigate the in vivo stability of the MLVA16 markers. Results Three-hundred and seventy-five clinical samples, including 275 vaginal swabs and 100 milk samples, were cultured from a brucellosis outbreak in a cattle herd, which adopted RB51 vaccination and test-and-slaughter policies. Thirty-seven B. abortus isolates were obtained, eight from milk and twenty-nine from post-partum/abortion vaginal swabs, which were submitted to biotyping and genotyping by MLVA16. Twelve B. abortus isolates obtained from vaginal swabs were identified as RB51. Twenty four isolates, seven obtained from milk samples and seventeen from vaginal swabs, were identified as B. abortus biovar 3, while one isolate from vaginal swabs was identified as B. abortus biovar 1. Three distinct genotypes were observed during the brucellosis outbreak: RB observed in all isolates identified as RB51; W observed in all B. abortus biovar 3 isolates; and Z observed in the single B. abortus biovar 1 isolate. Epidemiological and molecular data show that the B. abortus biovar 1 genotype Z strain is not related to the B. abortus biovar 3 genotype W isolates, and represents a new introduction B. abortus during the outbreak. Conclusions The results of the present study on typing of multiple clinical B. abortus isolates from the same outbreak over a sixteen month period indicate the in vivo stability of MLVA16 markers, a low genetic diversity among B. abortus isolates and the usefulness of MLVA16 for epidemiological studies of bovine brucellosis. PMID:25015840

Application of linear mixed models to study genetic stability of height and body mass index across countries and time.

PubMed

Trzaskowski, Maciej; Lichtenstein, Paul; Magnusson, Patrik K; Pedersen, Nancy L; Plomin, Robert

2016-01-27

It is now possible to estimate genetic correlations between two independent samples when there is no overlapping phenotypic information. We applied the latest bivariate genomic methods to children in the UK and older adults in Sweden to ask two questions. Are the same variants driving individual differences in anthropometric traits in these two populations, and are these variants as important in childhood as they are later in life? A sample of 3152 11-year-old children in the UK was compared with a sample of 6813 adults with an average age of 65 in Sweden. Genotypes were imputed from 1000 genomes with combined 9 767 136 single nucleotide polymorphisms meeting quality control criteria in both samples. Two cross-sample GCTA-GREML analyses and linkage disequilibrium (LD) score regressions were conducted to assess genetic correlations across more than 50 years: child versus adult height and child versus adult body mass index (BMI). Consistency of effects was tested using the recently proposed polygenic scoring method. For height, GCTA-GREML and LD score indicated strong genetic stability between children and adults, 0.58 (0.16) and 1.335 (1.09), respectively. For BMI, both methods produced similarly strong estimates of genetic stability 0.75 (0.26) and 0.855 (0.49), respectively. In height, adult polygenic score explained 60% of genetic variance in childhood and 10% of variance in BMI. Here we replicated and extended previous findings of longitudinal genetic stability in anthropometric traits to cross-cultural dimensions, and showed that for height but not BMI these variants are as important in childhood as they are in adulthood. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example. PMID:23515190

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example.

Is the child 'father of the man'? evaluating the stability of genetic influences across development.

PubMed

Ronald, Angelica

2011-11-01

This selective review considers findings in genetic research that have shed light on how genes operate across development. We will address the question of whether the child is 'father of the Man' from a genetic perspective. In other words, do the same genetic influences affect the same traits across development? Using a 'taster menu' approach and prioritizing newer findings on cognitive and behavioral traits, examples from the following genetic disciplines will be discussed: (a) developmental quantitative genetics (such as longitudinal twin studies), (b) neurodevelopmental genetic syndromes with known genetic causes (such as Williams syndrome), (c) developmental candidate gene studies (such as those that link infant and adult populations), (d) developmental genome-wide association studies (GWAS), and (e) DNA resequencing. Evidence presented here suggests that there is considerable genetic stability of cognitive and behavioral traits across development, but there is also evidence for genetic change. Quantitative genetic studies have a long history of assessing genetic continuity and change across development. It is now time for the newer, more technology-enabled fields such as GWAS and DNA resequencing also to take on board the dynamic nature of human behavior. 2011 Blackwell Publishing Ltd.

Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment.

PubMed

de Santana, Marlon G Veloso; Neves, Patrícia C C; dos Santos, Juliana Ribeiro; Lima, Noemia S; dos Santos, Alexandre A C; Watkins, David I; Galler, Ricardo; Bonaldo, Myrna C

2014-03-01

We have previously designed a method to construct viable recombinant Yellow Fever (YF) 17D viruses expressing heterologous polypeptides including part of the Simian Immunodeficiency Virus (SIV) Gag protein. However, the expressed region, encompassing amino acid residues from 45 to 269, was genetically unstable. In this study, we improved the genetic stability of this recombinant YF 17D virus by introducing mutations in the IRES element localized at the 5' end of the SIV gag gene. The new stable recombinant virus elicited adaptive immune responses similar to those induced by the original recombinant virus. It is, therefore, possible to increase recombinant stability by removing functional motifs from the insert that may have deleterious effects on recombinant YF viral fitness. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of mutant phenotypes associated with loss of individual microRNAs in sensitized genetic backgrounds in Caenorhabditis elegans

PubMed Central

Brenner, John L.; Jasiewicz, Kristen L.; Fahley, Alisha F.; Kemp, Benedict J.; Abbott, Allison L.

2010-01-01

Summary MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the translation and/or the stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single gene knockouts did not result in detectable mutant phenotypes [1]. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes [2]. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways [3]. Using these two approaches, mutant phenotypes were identified for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis. PMID:20579881

Microarray hybridization for assessment of the genetic stability of chimeric West Nile/dengue 4 virus.

PubMed

Laassri, Majid; Bidzhieva, Bella; Speicher, James; Pletnev, Alexander G; Chumakov, Konstantin

2011-05-01

Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located in the envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G(2337) C (Met(457) Ile) in the E gene and A(6751) G (Lys(125) Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this article could be useful for monitoring the molecular consistency and quality control of vaccine strains. Copyright © 2011 Wiley-Liss, Inc.

Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wyatt, Linda S.; Belyakov, Igor M.; Earl, Patricia L.

2008-03-15

During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env, a few viral foci stained very prominently. Virus cloned from such foci replicated to higher titers than the parent and displayed enhanced genetic stability on passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env gene of the mutant that caused a frame shift and truncation of 115 amino acids from the cytoplasmic domain. The truncated Env was more highly expressed on the cell surface, induced higher antibody responses than the full-length Env, reacted with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor-dependent fusion. Intramuscular (IM), intradermalmore » (ID) needleless, and intrarectal (IR) catheter inoculations gave comparable serum IgG responses. However, intraoral (IO) needleless injector route gave the highest IgA in lung washings and IR gave the highest IgA and IgG responses in fecal extracts. Induction of CTL responses in the spleens of individual mice as assayed by intracellular cytokine staining was similar with both the full-length and truncated Env constructs. Induction of acute and memory CTL in the spleens of mice immunized with the truncated Env construct by ID, IO, and IR routes was comparable and higher than by the IM route, but only the IR route induced CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines.« less

Microarray Hybridization for Assessment of the Genetic Stability of Chimeric West Nile/Dengue 4 Virus

PubMed Central

Laassri, Majid; Bidzhieva, Bella; Speicher, James; Pletnev, Alexander G.; Chumakov, Konstantin

2012-01-01

Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located in the envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G2337C (Met457Ile) in the E gene and A6751G (Lys125Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this paper could be useful for monitoring the molecular consistency and quality control of vaccine strains. PMID:21360544

Stabilization process in Saccharomyces intra and interspecific hybrids in fermentative conditions.

PubMed

Pérez-Través, Laura; Lopes, Christian A; Barrio, Eladio; Querol, Amparo

2014-12-01

We evaluated the genetic stabilization of artificial intra- (Saccharomyces cerevisiae) and interspecific (S. cerevisiae × S. kudriavzevii) hybrids under wine fermentative conditions. Large-scale transitions in genome size and genome reorganizations were observed during this process. Interspecific hybrids seem to need fewer generations to reach genetic stability than intraspecific hybrids. The largest number of molecular patterns recovered among the derived clones was observed for intraspecific hybrids, particularly for those obtained by rare-mating. Molecular marker analyses revealed that unstable clones could change during the industrial process to obtain active dry yeast. When no changes in molecular markers and ploidy were observed after this process, no changes in genetic composition were confirmed by comparative genome hybridization, considering the clone as a stable hybrid. According to our results, under these conditions, fermentation steps 3 and 5 (30-50 generations) would suffice to obtain genetically stable interspecific and intraspecific hybrids, respectively. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review.

PubMed

Hannigan, L J; Walaker, N; Waszczuk, M A; McAdams, T A; Eley, T C

2017-01-01

Emotional and behavioural problems in childhood and adolescence can be chronic and are predictive of future psychiatric problems. Understanding what factors drive the development and maintenance of these problems is therefore crucial. Longitudinal behavioural genetic studies using twin, sibling or adoption data can be used to explore the developmental aetiology of stability and change in childhood and adolescent psychopathology. We present a systematic review of longitudinal, behavioural genetic analyses of emotional and behavioural problems between ages 0 to 18 years. We identified 58 studies, of which 19 examined emotional problems, 30 examined behavioural problems, and 9 examined both. In the majority of studies, stability in emotional and behavioural problems was primarily genetically influenced. Stable environmental factors were also widely found, although these typically played a smaller role. Both genetic and environmental factors were involved in change across development. We discuss the findings in the context of the wider developmental literature and make recommendations for future research.

Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review

PubMed Central

Hannigan, L.J.; Walaker, N.; Waszczuk, M.A.; McAdams, T.A.; Eley, T.C.

2016-01-01

Emotional and behavioural problems in childhood and adolescence can be chronic and are predictive of future psychiatric problems. Understanding what factors drive the development and maintenance of these problems is therefore crucial. Longitudinal behavioural genetic studies using twin, sibling or adoption data can be used to explore the developmental aetiology of stability and change in childhood and adolescent psychopathology. We present a systematic review of longitudinal, behavioural genetic analyses of emotional and behavioural problems between ages 0 to 18 years. We identified 58 studies, of which 19 examined emotional problems, 30 examined behavioural problems, and 9 examined both. In the majority of studies, stability in emotional and behavioural problems was primarily genetically influenced. Stable environmental factors were also widely found, although these typically played a smaller role. Both genetic and environmental factors were involved in change across development. We discuss the findings in the context of the wider developmental literature and make recommendations for future research. PMID:28337341

Genetic and adoptive motherhood: stress, marital relationship, and child care support.

PubMed

Howat-Rodrigues, Anna Beatriz Carnielli; Tokumaru, Rosana Suemi; de Amorim, Thalita Novaes; Garcia, Agnaldo; Izar, Patrícia

2013-01-01

In this paper we characterize adoptive and genetic motherhood with or without stress indicators. Participants were 86 mothers (36 adoptive, 50 genetic) with children from 0 to 12 years old. They answered questions about focal child and mother profile, marital relationship, child care support and the Lipp's Stress Symptoms Inventory for Adults. Results showed that mothers in both groups reported child care support, but there was more participation of nonrelatives in the care of adoptive children and relatives in the care of genetic children. There was greater marital stability and less conflict with the arrival of the child in the adoptive families and predominance of stress indicators in genetic mothers. We concluded that, although there are differences between adoptive and genetic motherhood, these do not imply advantages for one versus the other. Moreover, marital stability related to the adoption process and sociodemographic characteristics of adoptive mothers may have contributed to lower prevalence of stress.

Reduced genetic variance among high fitness individuals: inferring stabilizing selection on male sexual displays in Drosophila serrata.

PubMed

Sztepanacz, Jacqueline L; Rundle, Howard D

2012-10-01

Directional selection is prevalent in nature, yet phenotypes tend to remain relatively constant, suggesting a limit to trait evolution. However, the genetic basis of this limit is unresolved. Given widespread pleiotropy, opposing selection on a trait may arise from the effects of the underlying alleles on other traits under selection, generating net stabilizing selection on trait genetic variance. These pleiotropic costs of trait exaggeration may arise through any number of other traits, making them hard to detect in phenotypic analyses. Stabilizing selection can be inferred, however, if genetic variance is greater among low- compared to high-fitness individuals. We extend a recently suggested approach to provide a direct test of a difference in genetic variance for a suite of cuticular hydrocarbons (CHCs) in Drosophila serrata. Despite strong directional sexual selection on these traits, genetic variance differed between high- and low-fitness individuals and was greater among the low-fitness males for seven of eight CHCs, significantly more than expected by chance. Univariate tests of a difference in genetic variance were nonsignificant but likely have low power. Our results suggest that further CHC exaggeration in D. serrata in response to sexual selection is limited by pleiotropic costs mediated through other traits. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Decadal stability in genetic variation and structure in the intertidal seaweed Fucus serratus (Heterokontophyta: Fucaceae).

PubMed

Jueterbock, Alexander; Coyer, James A; Olsen, Jeanine L; Hoarau, Galice

2018-06-15

The spatial distribution of genetic diversity and structure has important implications for conservation as it reveals a species' strong and weak points with regard to stability and evolutionary capacity. Temporal genetic stability is rarely tested in marine species other than commercially important fishes, but is crucial for the utility of temporal snapshots in conservation management. High and stable diversity can help to mitigate the predicted northward range shift of seaweeds under the impact of climate change. Given the key ecological role of fucoid seaweeds along rocky shores, the positive effect of genetic diversity may reach beyond the species level to stabilize the entire intertidal ecosystem along the temperate North Atlantic. In this study, we estimated the effective population size, as well as temporal changes in genetic structure and diversity of the seaweed F. serratus using 22 microsatellite markers. Samples were taken across latitudes and a range of temperature regimes at seven locations with decadal sampling (2000 and 2010). Across latitudes, genetic structure and diversity remained stable over 5-10 generations. Stable small-scale structure enhanced regional diversity throughout the species' range. In accordance with its biogeographic history, effective population size and diversity peaked in the species' mid-range in Brittany (France), and declined towards its leading and trailing edge to the north and south. At the species' southern edge, multi-locus-heterozygosity displayed a strong decline from 1999 to 2010. Temporally stable genetic structure over small spatial scales is a potential driver for local adaptation and species radiation in the genus Fucus. Survival and adaptation of the low-diversity leading edge of F. serratus may be enhanced by regional gene flow and 'surfing' of favorable mutations or impaired by the accumulation of deleterious mutations. Our results have clear implications for the conservation of F. serratus at its genetically unique southern edge in Northwest Iberia, where increasing temperatures are likely the major cause for the decline not only of F. serratus, but also other intertidal and subtidal macroalgae. We expect that F. serratus will disappear from Northwest Iberia by 2100 if genetic rescue is not induced by the influx of genetic variation from Brittany.

The stability of colorectal cancer mathematical models

NASA Astrophysics Data System (ADS)

Khairudin, Nur Izzati; Abdullah, Farah Aini

2013-04-01

Colorectal cancer is one of the most common types of cancer. To better understand about the kinetics of cancer growth, mathematical models are used to provide insight into the progression of this natural process which enables physicians and oncologists to determine optimal radiation and chemotherapy schedules and develop a prognosis, both of which are indispensable for treating cancer. This thesis investigates the stability of colorectal cancer mathematical models. We found that continuous saturating feedback is the best available model of colorectal cancer growth. We also performed stability analysis. The result shows that cancer progress in sequence of genetic mutations or epigenetic which lead to a very large number of cells population until become unbounded. The cell population growth initiate and its saturating feedback is overcome when mutation changes causing the net per-capita growth rate of stem or transit cells exceed critical threshold.

Stability and change in temperament during adolescence.

PubMed

Ganiban, Jody M; Saudino, Kimberly J; Ulbricht, Jennifer; Neiderhiser, Jenae M; Reiss, David

2008-07-01

This study assessed genetic and environmental contributions to temperament during adolescence within the Nonshared Environment and Adolescent Development project (NEAD; D. Reiss, J. M. Neiderhiser, E. M. Hetherington, & R. Plomin, 2000). NEAD is a national study that includes twins and other sibling types who vary in regard to genetic relatedness. Seven hundred twenty sibling pairs (aged 12.1-13.5 years) participated at Time 1, and 395 sibling pairs (aged 14.7-16.2 years) participated again at Time 2. At both Times, mothers and fathers rated their children's temperament (emotionality, activity, sociability, and shyness). At Times 1 and 2, genetic and nonshared environmental factors accounted for variance in temperament, whereas shared environmental contributions were negligible. However, at Time 1, genetic contributions were inflated, and shared environmental contributions were masked if sibling contrast effects were not taken into account. At Time 2, sibling interaction effects had little impact on estimates of genetic and environmental contributions to temperament. Last, temperament stability was primarily explained by genetic factors, whereas both genetic and nonshared environmental factors accounted for change.

Identification of the molecular genetic basis of the low palmitic acid seed oil trait in soybean mutant line RG3 and association analysis of molecular markers with elevated seed stearic acid and reduced seed palmitic acid

USDA-ARS?s Scientific Manuscript database

The fatty acid composition of vegetable oil is becoming increasingly critical for the ultimate functionality and utilization in foods and industrial products. Partial chemical hydrogenation of soybean oil increases oxidative stability and shelf life but also results in the introduction of trans fats...

An efficient in planta transformation of Jatropha curcas (L.) and multiplication of transformed plants through in vivo grafting.

PubMed

Jaganath, Balusamy; Subramanyam, Kondeti; Mayavan, Subramanian; Karthik, Sivabalan; Elayaraja, Dhandapani; Udayakumar, Rajangam; Manickavasagam, Markandan; Ganapathi, Andy

2014-05-01

An efficient and reproducible Agrobacterium-mediated in planta transformation was developed in Jatropha curcas. The various factors affecting J. curcas in planta transformation were optimized, including decapitation, Agrobacterium strain, pin-pricking, vacuum infiltration duration and vacuum pressure. Simple vegetative in vivo cleft grafting method was adopted in the multiplication of transformants without the aid of tissue culture. Among the various parameters evaluated, decapitated plants on pin-pricking and vacuum infiltrated at 250 mmHg for 3 min with the Agrobacterium strain EHA 105 harbouring the binary vector pGA 492 was proved to be efficient in all terms with a transformation efficiency of 62.66%. Transgene integration was evinced by the GUS histochemical analysis, and the GUS positive plants were subjected to grafting. Putatively transformed J. curcas served as "Scion" and the wild type J. curcas plant severed as "Stock". There was no occurrence of graft rejection and the plants were then confirmed by GUS histochemical analysis, polymerase chain reaction (PCR) and Southern hybridization. Genetic stability of the grafted plants was evaluated by using randomly amplified polymorphic DNA (RAPD), marker which showed 100% genetic stability between mother and grafted plants. Thus, an efficient in planta transformation and grafting based multiplication of J. curcas was established.

The DNA of coral reef biodiversity: predicting and protecting genetic diversity of reef assemblages

PubMed Central

Gaggiotti, Oscar E.; Treml, Eric A.; Wren, Johanna L. K.; Donovan, Mary K.; Toonen, Robert J.

2016-01-01

Conservation of ecological communities requires deepening our understanding of genetic diversity patterns and drivers at community-wide scales. Here, we use seascape genetic analysis of a diversity metric, allelic richness (AR), for 47 reef species sampled across 13 Hawaiian Islands to empirically demonstrate that large reefs high in coral cover harbour the greatest genetic diversity on average. We found that a species's life history (e.g. depth range and herbivory) mediates response of genetic diversity to seascape drivers in logical ways. Furthermore, a metric of combined multi-species AR showed strong coupling to species richness and habitat area, quality and stability that few species showed individually. We hypothesize that macro-ecological forces and species interactions, by mediating species turnover and occupancy (and thus a site's mean effective population size), influence the aggregate genetic diversity of a site, potentially allowing it to behave as an apparent emergent trait that is shaped by the dominant seascape drivers. The results highlight inherent feedbacks between ecology and genetics, raise concern that genetic resilience of entire reef communities is compromised by factors that reduce coral cover or available habitat, including thermal stress, and provide a foundation for new strategies for monitoring and preserving biodiversity of entire reef ecosystems. PMID:27122569

The DNA of coral reef biodiversity: predicting and protecting genetic diversity of reef assemblages.

PubMed

Selkoe, Kimberly A; Gaggiotti, Oscar E; Treml, Eric A; Wren, Johanna L K; Donovan, Mary K; Toonen, Robert J

2016-04-27

Conservation of ecological communities requires deepening our understanding of genetic diversity patterns and drivers at community-wide scales. Here, we use seascape genetic analysis of a diversity metric, allelic richness (AR), for 47 reef species sampled across 13 Hawaiian Islands to empirically demonstrate that large reefs high in coral cover harbour the greatest genetic diversity on average. We found that a species's life history (e.g. depth range and herbivory) mediates response of genetic diversity to seascape drivers in logical ways. Furthermore, a metric of combined multi-species AR showed strong coupling to species richness and habitat area, quality and stability that few species showed individually. We hypothesize that macro-ecological forces and species interactions, by mediating species turnover and occupancy (and thus a site's mean effective population size), influence the aggregate genetic diversity of a site, potentially allowing it to behave as an apparent emergent trait that is shaped by the dominant seascape drivers. The results highlight inherent feedbacks between ecology and genetics, raise concern that genetic resilience of entire reef communities is compromised by factors that reduce coral cover or available habitat, including thermal stress, and provide a foundation for new strategies for monitoring and preserving biodiversity of entire reef ecosystems. © 2016 The Authors.

Etiology of Stability and Growth of Internalizing and Externalizing Behavior Problems Across Childhood and Adolescence.

PubMed

Hatoum, Alexander S; Rhee, Soo Hyun; Corley, Robin P; Hewitt, John K; Friedman, Naomi P

2018-04-20

Internalizing and externalizing behaviors are heritable, and show genetic stability during childhood and adolescence. Less work has explored how genes influence individual differences in developmental trajectories. We estimated ACE biometrical latent growth curve models for the Teacher Report Form (TRF) and parent Child Behavior Checklist (CBCL) internalizing and externalizing scales from ages 7 to 16 years in 408 twin pairs from the Colorado Longitudinal Twin Study. We found that Intercept factors were highly heritable for both internalizing and externalizing behaviors (a2 = .61-.92), with small and nonsignificant environmental influences for teacher-rated data but significant nonshared environmental influences for parent-rated data. There was some evidence of heritability of decline in internalizing behavior (Slopes for teacher and parent ratings), but the Slope genetic variance was almost entirely shared with that for the Intercept when different than zero. These results suggest that genetic effects on these developmental trajectories operate primarily on initial levels and stability, with no significant unique genetic influences for change. Finally, cross-rater analyses of the growth factor scores revealed moderate to large genetic and environmental associations between growth factors derived from parents' and teachers' ratings, particularly the Intercepts.

[Genetic improvement of cotton varieties in Huang-Huai region in China since 1950's. III. Improvement on agronomy properties, disease resistance and stability].

PubMed

Jiang, B G; Kong, F L; Zhang, Q Y; Yang, F X; Jiang, R Q

2000-01-01

Data from a set of 5-location and 2-year experiments on 10 representative historical cotton varieties and the data of Huang-Huai Regional Cotton Trials from 1973 to 1996 were analyzed to estimate the effects of genetic improvement in agronomy properties, disease resistance and stability of cotton in Huang-Huai Region in China. The results indicated that a great genetic progress of earliness and disease resistance had been achieved by breeding programs since 1950's. The maturity was shortened 3-5 days; The rate of preforst yield was increased about 7 percentages. The problem of resistance to Fususium wilt has been solved and the resistance to Verticillum wilt was improving. Some progress in stability of cotton varieties also has been achieved by breeding programs since 1950.

Genetic identification and molecular modeling characterization reveal a novel PROM1 mutation in Stargardt4-like macular dystrophy

PubMed Central

Imani, Saber; Cheng, Jingliang; Shasaltaneh, Marzieh Dehghan; Wei, Chunli; Yang, Lisha; Fu, Shangyi; Zou, Hui; Khan, Md. Asaduzzaman; Zhang, Xianqin; Chen, Hanchun; Zhang, Dianzheng; Duan, Chengxia; Lv, Hongbin; Li, Yumei; Chen, Rui; Fu, Junjiang

2018-01-01

Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder. In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD. We found a novel heterozygous missense mutation, c.734T>C (p.L245P) in the PROM1 gene. Structurally, this mutation most likely impairs PROM1 protein stability, flexibility, and amino acid interaction network after changing the amino acid residue Leucine into Proline in the basic helix-loop-helix leucine zipper domain. Molecular dynamic simulation and principal component analysis provide compelling evidence that this PROM1 mutation contributes to disease causativeness or susceptibility variants in patients with STGD4-like MD. Thus, this finding defines new approaches in genetic characterization, accurate diagnosis, and prevention of STGD4-like MD. PMID:29416601

Genetic characterization of Italian field strains of Schmallenberg virus based on N and NSs genes.

PubMed

Izzo, Francesca; Cosseddu, Gian Mario; Polci, Andrea; Iapaolo, Federica; Pinoni, Chiara; Capobianco Dondona, Andrea; Valleriani, Fabrizia; Monaco, Federica

2016-08-01

Following its first identification in Germany in 2011, the Schmallenberg virus (SBV) has rapidly spread to many other European countries. Despite the wide dissemination, the molecular characterization of the circulating strains is limited to German, Belgian, Dutch, and Swiss viruses. To fill this gap, partial genetic characterization of 15 Italian field strains was performed, based on S segment genes. Samples were collected in 2012 in two different regions where outbreaks occurred during distinct epidemic seasons. The comparative sequence analysis demonstrated a high molecular stability of the circulating viruses; nevertheless, we identified several variants of the N and NSs proteins not described in other SBV isolates circulating in Europe.

Genetic stability of a dengue vaccine based on chimeric yellow fever/dengue viruses.

PubMed

Mantel, N; Girerd, Y; Geny, C; Bernard, I; Pontvianne, J; Lang, J; Barban, V

2011-09-02

A tetravalent dengue vaccine based on four live, attenuated, chimeric viruses (CYD1-4), constructed by replacing the genes coding for premembrane (prM) and envelope (E) proteins of the yellow fever (YF)-17D vaccine strain with those of the four serotypes of dengue virus, is in clinical phase III evaluation. We assessed the vaccine's genetic stability by fully sequencing each vaccine virus throughout the development and manufacturing process. The four viruses displayed complete genetic stability, with no change from premaster seed lots to bulk lots. When pursuing the virus growth beyond bulk lots, a few genetic variations were observed. Usually both the initial nucleotide and the new one persisted, and mutations appeared after a relatively high number of virus duplication cycles (65-200, depending on position). Variations were concentrated in the prM-E and non-structural (NS)4B regions. PrM-E variations had no impact on lysis-plaque size or neurovirulence in mice. None of the variations located in the YF-17D-derived genes corresponded with reversion to the wild-type Yellow Fever sequence. Variations in NS4B likely reflect virus adaptation to Vero cells growth. A low to undetectable viremia has been reported previously [1-3] in vaccinated non-human and human primates. Combined with the data reported here about the genetic stability of the vaccine strains, the probability of in vivo emergence of mutant viruses appears very low. Copyright © 2011 Elsevier Ltd. All rights reserved.

The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood.

PubMed

Waszczuk, M A; Zavos, H M S; Gregory, A M; Eley, T C

2016-01-01

Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood. A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years. Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms. The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches.

The Stability of Genetic Determination from Age 2 to Age 9: A Longitudinal Twin Study.

ERIC Educational Resources Information Center

Lytton, Hugh; And Others

A longitudinal investigation of the social and cognitive development of male twins was conducted when twins were 2.5 years of age, and again when they were 8- to 10-years-old. This study was designed to re-examine the heritability of the traits studied at the earlier age and, thus, to address the question of the stability of genetic determination.…

Difficult temperament and negative parenting in early childhood: a genetically informed cross-lagged analysis.

PubMed

Micalizzi, Lauren; Wang, Manjie; Saudino, Kimberly J

2017-03-01

A genetically informed longitudinal cross-lagged model was applied to twin data to explore etiological links between difficult temperament and negative parenting in early childhood. The sample comprised 313 monozygotic (MZ) and dizygotic (DZ) twin pairs. Difficult temperament and negative parenting were assessed at ages 2 and 3 using parent ratings. Both constructs were interrelated within and across age (rs .34-.47) and showed substantial stability (rs .65-.68). Difficult temperament and negative parenting were influenced by genetic and environmental factors at ages 2 and 3. The genetic and nonshared environmental correlations (rs .21-.76) at both ages suggest overlap at the level of etiology between the phenotypes. Significant bidirectional associations between difficult temperament and negative parenting were found. The cross-lagged association from difficult temperament at age 2 to negative parenting at age 3 and from negative parenting at age 2 and difficult temperament at age 3 were due to genetic, shared environmental, and nonshared environmental factors. Substantial novel genetic and nonshared environmental influences emerged at age 3 and suggest change in the etiology of these constructs over time. © 2015 John Wiley & Sons Ltd.

Rhizobium etli and Rhizobium gallicum Nodulate Common Bean (Phaseolus vulgaris) in a Traditionally Managed Milpa Plot in Mexico: Population Genetics and Biogeographic Implications

PubMed Central

Silva, Claudia; Vinuesa, Pablo; Eguiarte, Luis E.; Martínez-Romero, Esperanza; Souza, Valeria

2003-01-01

The stability of the genetic structure of rhizobial populations nodulating Phaseolus vulgaris cultivated in a traditionally managed milpa plot in Mexico was studied over three consecutive years. The set of molecular markers analyzed (including partial rrs, glnII, nifH, and nodB sequences), along with host range experiments, placed the isolates examined in Rhizobium etli bv. phaseoli and Rhizobium gallicum bv. gallicum. Cluster analysis of multilocus enzyme electrophoresis and plasmid profile data separated the two species and identified numerically dominant clones within each of them. Population genetic analyses showed that there was high genetic differentiation between the two species and that there was low intrapopulation differentiation of the species over the 3 years. The results of linkage disequilibrium analyses are consistent with an epidemic genetic structure for both species, with frequent genetic exchange taking place within conspecific populations but not between the R. etli and R. gallicum populations. A subsample of isolates was selected and used for 16S ribosomal DNA PCR-restriction fragment length polymorphism analysis, nifH copy number determination, and host range experiments. Plasmid profiles and nifH hybridization patterns also revealed the occurrence of lateral plasmid transfer among distinct multilocus genotypes within species but not between species. Both species were recovered from nodules of the same plants, indicating that mechanisms other than host, spatial, or temporal isolation may account for the genetic barrier between the species. The biogeographic implications of finding an R. gallicum bv. gallicum population nodulating common bean in America are discussed. PMID:12571008

Characterization of Genomic Island 3 and Genetic Variability of Chilean Field Strains of Brucella abortus▿

PubMed Central

Céspedes, Sandra; Salgado, Paulina; Valenzuela, Patricio; Vidal, Roberto; Oñate, Angel A.

2011-01-01

One of the capabilities developed by bacteria is the ability to gain large fragments of DNA from other bacteria or to lose portions of their own genomes. Among these exchangeable fragments are the genomic islands (GIs). Nine GIs have been identified in Brucella, and genomic island 3 (GI-3) is shared by two pathogenic species, B. melitensis and B. abortus. GI-3 encodes mostly unknown proteins. One of the aims of this study was to perform pulsed-field gel electrophoresis (PFGE) on field isolates of B. abortus from Chile to determine whether these isolates are clonally related. Furthermore, we focused on the characterization of GI-3, studying its organization and the genetic conservation of the GI-3 sequence using techniques such as tiling-path PCR (TP-PCR) and restriction fragment length polymorphism-PCR (RFLP-PCR). Our results, after PFGE was performed on 69 field isolates of B. abortus from Chile, showed that the strains were genetically homogeneous. To increase the power of genetic discrimination among these strains, we used multiple locus variable-number tandem-repeat (VNTR) analysis with 16 loci (MLVA-16). The results obtained by MLVA-16 showed that the strains of B. abortus were genetically heterogeneous and that most of them clustered according to their geographic origin. Of the genetic loci studied, panel 2B was the one describing the highest diversity in the analysis, as well as locus Bruce19 in panel 2A. In relation to the study of GI-3, our experimental analysis by TP-PCR identified and confirmed that GI-3 is present in all wild strains of B. abortus, demonstrating the high stability of gene cluster GI-3 in Chilean field strains. PMID:21543580

Genetic and environmental influences on affiliation with deviant peers during adolescence and early adulthood.

PubMed

Tarantino, Nicholas; Tully, Erin C; Garcia, Sarah E; South, Susan; Iacono, William G; McGue, Matt

2014-03-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youths exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence has suggested that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3 discrete ages: 15, 18, and 21 years of age. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping, whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Genetic and Environmental Influences on Affiliation with Deviant Peers during Adolescence and Early Adulthood

PubMed Central

Tarantino, Nicholas; Tully, Erin C.; Garcia, Sarah E.; South, Susan; Iacono, William G.; McGue, Matt

2014-01-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youth exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence suggests that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at three discrete ages-15-, 18-, and 21-years-old. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PMID:24015689

Temporal genetic analysis of the endangered tidewater goby: extinction-colonization dynamics or drift in isolation?

PubMed

Kinziger, Andrew P; Hellmair, Michael; McCraney, W Tyler; Jacobs, David K; Goldsmith, Greg

2015-11-01

Extinction and colonization dynamics are critical to understanding the evolution and conservation of metapopulations. However, traditional field studies of extinction-colonization are potentially fraught with detection bias and have rarely been validated. Here, we provide a comparison of molecular and field-based approaches for assessment of the extinction-colonization dynamics of tidewater goby (Eucyclogobius newberryi) in northern California. Our analysis of temporal genetic variation across 14 northern California tidewater goby populations failed to recover genetic change expected with extinction-colonization cycles. Similarly, analysis of site occupancy data from field studies (94 sites) indicated that extinction and colonization are very infrequent for our study populations. Comparison of the approaches indicated field data were subject to imperfect detection, and falsely implied extinction-colonization cycles in several instances. For northern California populations of tidewater goby, we interpret the strong genetic differentiation between populations and high degree of within-site temporal stability as consistent with a model of drift in the absence of migration, at least over the past 20-30 years. Our findings show that tidewater goby exhibit different population structures across their geographic range (extinction-colonization dynamics in the south vs. drift in isolation in the north). For northern populations, natural dispersal is too infrequent to be considered a viable approach for recolonizing extirpated populations, suggesting that species recovery will likely depend on artificial translocation in this region. More broadly, this work illustrates that temporal genetic analysis can be used in combination with field data to strengthen inference of extinction-colonization dynamics or as a stand-alone tool when field data are lacking. © 2015 John Wiley & Sons Ltd.

Surgical wound segmentation based on adaptive threshold edge detection and genetic algorithm

NASA Astrophysics Data System (ADS)

Shih, Hsueh-Fu; Ho, Te-Wei; Hsu, Jui-Tse; Chang, Chun-Che; Lai, Feipei; Wu, Jin-Ming

2017-02-01

Postsurgical wound care has a great impact on patients' prognosis. It often takes few days, even few weeks, for the wound to stabilize, which incurs a great cost of health care and nursing resources. To assess the wound condition and diagnosis, it is important to segment out the wound region for further analysis. However, the scenario of this strategy often consists of complicated background and noise. In this study, we propose a wound segmentation algorithm based on Canny edge detector and genetic algorithm with an unsupervised evaluation function. The results were evaluated by the 112 clinical images, and 94.3% of images were correctly segmented. The judgment was based on the evaluation of experimented medical doctors. This capability to extract complete wound regions, makes it possible to conduct further image analysis such as intelligent recovery evaluation and automatic infection requirements.

Temporal Stability of Genetic Variability and Differentiation in the Three-Spined Stickleback (Gasterosteus aculeatus)

PubMed Central

DeFaveri, Jacquelin; Merilä, Juha

2015-01-01

Temporal variation in allele frequencies, whether caused by deterministic or stochastic forces, can inform us about interesting demographic and evolutionary phenomena occurring in wild populations. In spite of the continued surge of interest in the genetics of three-spined stickleback (Gasterosteus aculeatus) populations, little attention has been paid towards the temporal stability of allele frequency distributions, and whether there are consistent differences in effective size (Ne) of local populations. We investigated temporal stability of genetic variability and differentiation in 15 microsatellite loci within and among eight collection sites of varying habitat type, surveyed twice over a six-year time period. In addition, Nes were estimated with the expectation that they would be lowest in isolated ponds, intermediate in larger lakes and largest in open marine sites. In spite of the marked differences in genetic variability and differentiation among the study sites, the temporal differences in allele frequencies, as well as measures of genetic diversity and differentiation, were negligible. Accordingly, the Ne estimates were temporally stable, but tended to be lower in ponds than in lake or marine habitats. Hence, we conclude that allele frequencies in putatively neutral markers in three-spined sticklebacks seem to be temporally stable – at least over periods of few generations – across a wide range of habitat types differing markedly in levels of genetic variability, effective population size and gene flow. PMID:25853707

Temporal stability of genetic variability and differentiation in the three-spined stickleback (Gasterosteus aculeatus).

PubMed

DeFaveri, Jacquelin; Merilä, Juha

2015-01-01

Temporal variation in allele frequencies, whether caused by deterministic or stochastic forces, can inform us about interesting demographic and evolutionary phenomena occurring in wild populations. In spite of the continued surge of interest in the genetics of three-spined stickleback (Gasterosteus aculeatus) populations, little attention has been paid towards the temporal stability of allele frequency distributions, and whether there are consistent differences in effective size (Ne) of local populations. We investigated temporal stability of genetic variability and differentiation in 15 microsatellite loci within and among eight collection sites of varying habitat type, surveyed twice over a six-year time period. In addition, Nes were estimated with the expectation that they would be lowest in isolated ponds, intermediate in larger lakes and largest in open marine sites. In spite of the marked differences in genetic variability and differentiation among the study sites, the temporal differences in allele frequencies, as well as measures of genetic diversity and differentiation, were negligible. Accordingly, the Ne estimates were temporally stable, but tended to be lower in ponds than in lake or marine habitats. Hence, we conclude that allele frequencies in putatively neutral markers in three-spined sticklebacks seem to be temporally stable - at least over periods of few generations - across a wide range of habitat types differing markedly in levels of genetic variability, effective population size and gene flow.

Complementary effects of species and genetic diversity on productivity and stability of sown grasslands.

PubMed

Prieto, Iván; Violle, Cyrille; Barre, Philippe; Durand, Jean-Louis; Ghesquiere, Marc; Litrico, Isabelle

2015-03-30

Plant species diversity regulates the productivity(1-3) and stability(2,4) of natural ecosystems, along with their resilience to disturbance(5,6). The influence of species diversity on the productivity of agronomic systems is less clear(7-10). Plant genetic diversity is also suspected to influence ecosystem function(3,11-14), although empirical evidence is scarce. Given the large range of genotypes that can be generated per species through artificial selection, genetic diversity is a potentially important leverage of productivity in cultivated systems. Here we assess the effect of species and genetic diversity on the production and sustainable supply of livestock fodder in sown grasslands, comprising single and multispecies assemblages characterized by different levels of genetic diversity, exposed to drought and non-drought conditions. Multispecies assemblages proved more productive than monocultures when subject to drought, regardless of the number of genotypes per species present. Conversely, the temporal stability of production increased only with the number of genotypes present under both drought and non-drought conditions, and was unaffected by the number of species. We conclude that taxonomic and genetic diversity can play complementary roles when it comes to optimizing livestock fodder production in managed grasslands, and suggest that both levels of diversity should be considered in plant breeding programmes designed to boost the productivity and resilience of managed grasslands in the face of increasing environmental hazards.

Optimality and stability of symmetric evolutionary games with applications in genetic selection.

PubMed

Huang, Yuanyuan; Hao, Yiping; Wang, Min; Zhou, Wen; Wu, Zhijun

2015-06-01

Symmetric evolutionary games, i.e., evolutionary games with symmetric fitness matrices, have important applications in population genetics, where they can be used to model for example the selection and evolution of the genotypes of a given population. In this paper, we review the theory for obtaining optimal and stable strategies for symmetric evolutionary games, and provide some new proofs and computational methods. In particular, we review the relationship between the symmetric evolutionary game and the generalized knapsack problem, and discuss the first and second order necessary and sufficient conditions that can be derived from this relationship for testing the optimality and stability of the strategies. Some of the conditions are given in different forms from those in previous work and can be verified more efficiently. We also derive more efficient computational methods for the evaluation of the conditions than conventional approaches. We demonstrate how these conditions can be applied to justifying the strategies and their stabilities for a special class of genetic selection games including some in the study of genetic disorders.

Genetic variability in krill.

PubMed

Valentine, J W; Ayala, F J

1976-02-01

We have estimated genetic variability by gel electrophoresis in three species of krill, genus Euphausia (Arthropoda: Crustacea). Genetic variability is low where trophic resources are most seasonal, and high where trophic resources are most stable. Simlar trends have been found in benthic marine invertebrates. The observed trends of genetic variability do not correlate with trends in the stability of physical environment parameters.

Genetic and epigenetic stability of cryopreserved and cold-stored hops (Humulus lupulus L.).

PubMed

Peredo, Elena L; Arroyo-García, Rosa; Reed, Barbara M; Revilla, M Angeles

2008-12-01

Conventional cold storage and cryopreservation methods for hops (Humulus lupulus L.) are available but, to our knowledge, the genetic and epigenetic stability of the recovered plants have not been tested. This study analyzed 51 accessions of hop using the molecular techniques, Random Amplified DNA Polymorphism (RAPD) and Amplified Fragment Length Polymorphism (AFLP), revealing no genetic variation among greenhouse-grown controls and cold stored or cryopreserved plants. Epigenetic stability was evaluated using Methylation Sensitive Amplified Polymorphism (MSAP). Over 36% of the loci were polymorphic when the cold and cryo-treated plants were compared to greenhouse plants. The main changes were demethylation events and they were common to the cryopreserved and cold stored plants indicating the possible effect of the in vitro establishment process, an essential step in both protocols. Protocol-specific methylation patterns were also detected indicating that both methods produced epigenetic changes in plants following cold storage and cryopreservation.

Architecture of the wood-wide web: Rhizopogon spp. genets link multiple Douglas-fir cohorts.

PubMed

Beiler, Kevin J; Durall, Daniel M; Simard, Suzanne W; Maxwell, Sheri A; Kretzer, Annette M

2010-01-01

*The role of mycorrhizal networks in forest dynamics is poorly understood because of the elusiveness of their spatial structure. We mapped the belowground distribution of the fungi Rhizopogon vesiculosus and Rhizopogon vinicolor and interior Douglas-fir trees (Pseudotsuga menziesii var. glauca) to determine the architecture of a mycorrhizal network in a multi-aged old-growth forest. *Rhizopogon spp. mycorrhizas were collected within a 30 x 30 m plot. Trees and fungal genets were identified using multi-locus microsatellite DNA analysis. Tree genotypes from mycorrhizas were matched to reference trees aboveground. Two trees were considered linked if they shared the same fungal genet(s). *The two Rhizopogon species each formed 13-14 genets, each colonizing up to 19 trees in the plot. Rhizopogon vesiculosus genets were larger, occurred at greater depths, and linked more trees than genets of R. vinicolor. Multiple tree cohorts were linked, with young saplings established within the mycorrhizal network of Douglas-fir veterans. A strong positive relationship was found between tree size and connectivity, resulting in a scale-free network architecture with small-world properties. *This mycorrhizal network architecture suggests an efficient and robust network, where large trees play a foundational role in facilitating conspecific regeneration and stabilizing the ecosystem.

The Genetic Drift Inventory: A Tool for Measuring What Advanced Undergraduates Have Mastered about Genetic Drift

PubMed Central

Price, Rebecca M.; Andrews, Tessa C.; McElhinny, Teresa L.; Mead, Louise S.; Abraham, Joel K.; Thanukos, Anna; Perez, Kathryn E.

2014-01-01

Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures upper-division students’ understanding of this concept. We used an iterative approach that included extensive interviews and field tests involving 1723 students across five different undergraduate campuses. The GeDI consists of 22 agree–disagree statements that assess four key concepts and six misconceptions. Student scores ranged from 4/22 to 22/22. Statements ranged in mean difficulty from 0.29 to 0.80 and in discrimination from 0.09 to 0.46. The internal consistency, as measured with Cronbach's alpha, ranged from 0.58 to 0.88 across five iterations. Test–retest analysis resulted in a coefficient of stability of 0.82. The true–false format means that the GeDI can test how well students grasp key concepts central to understanding genetic drift, while simultaneously testing for the presence of misconceptions that indicate an incomplete understanding of genetic drift. The insights gained from this testing will, over time, allow us to improve instruction about this key component of evolution. PMID:24591505

Callous-unemotional behaviors in early childhood: Genetic and environmental contributions to stability and change.

PubMed

Flom, Megan; Saudino, Kimberly J

2017-10-01

Callous-unemotional (CU) behaviors demonstrate meaningful individual differences in early childhood, even in nonclinical samples with low mean levels of CU, but the factors underlying this variation have not been examined. This study investigated genetic and environmental contributions to individual differences and to sources of continuity and change in CU in toddler twins (145 monozygotic, 169 dizygotic) assessed at ages 2 and 3 years. CU, as assessed by the Child Behavior Checklist 1.5-5 (Achenbach & Rescorla, 2000), was moderately stable across age (r = .45, p < .0001). Longitudinal biometric analyses revealed genetic and nonshared environmental influences on CU at both ages, with no significant contribution from shared environmental factors. Stability from age 2 to 3 was due to genetic factors, whereas change was due to both genetic and nonshared environmental influences. This genetic and nonshared environmental change was substantial, suggesting malleability of CU in early childhood. Over 50% of the genetic influences and 100% of the nonshared environmental influences on CU at age 3 were independent of those that operated at age 2. Implications of novel sources of variance across age are discussed.

Model of continual metabolism species for estimating stability of CELSS and natural ecosystems

NASA Astrophysics Data System (ADS)

Bartsev, S. I.

Estimation of stability range of natural and man-made ecosystems is necessary for effective control of them However traditional ecological models usually underestimate stability of real ecosystems It takes place due to the usage of fixed stoichiometry model of metabolism The objective is in creating theoretical and mathematical models for adequate description of both man-made and natural ecological systems A concept of genetically fixed but metabolically flexible species is considered in the paper According to the concept the total flow of matter through ecological system is supported at almost constant level depending on energy income by flexibility of metabolic organization of genetic species It is shown introducing continual metabolism species extends the range of stability making its estimation more adequate to real ecological systems

40 CFR 158.2110 - Microbial pesticides data requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: genetic engineering techniques used; the identity of the inserted or deleted gene segment (base sequence... evaluate genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

40 CFR 158.2110 - Microbial pesticides data requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: genetic engineering techniques used; the identity of the inserted or deleted gene segment (base sequence... evaluate genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

40 CFR 158.2110 - Microbial pesticides data requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: genetic engineering techniques used; the identity of the inserted or deleted gene segment (base sequence... evaluate genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

40 CFR 158.2110 - Microbial pesticides data requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: genetic engineering techniques used; the identity of the inserted or deleted gene segment (base sequence... evaluate genetic stability and exchange; and selected Tier II environmental expression and toxicology tests. ...

White spot syndrome virus (WSSV) genome stability maintained over six passages through three different penaeid shrimp species.

PubMed

Sindhupriya, M; Saravanan, P; Otta, S K; Amarnath, C Bala; Arulraj, R; Bhuvaneswari, T; Praveena, P Ezhil; Jithendran, K P; Ponniah, A G

2014-08-21

White spot syndrome virus (WSSV) replicates rapidly, can be extremely pathogenic and is a common cause of mass mortality in cultured shrimp. Variable number tandem repeat (VNTR) sequences present in the open reading frame (ORF)94, ORF125 and ORF75 regions of the WSSV genome have been used widely as genetic markers in epidemiological studies. However, reports that VNTRs might evolve rapidly following even a single transmission through penaeid shrimp or other crustacean hosts have created confusion as to how VNTR data is interpreted. To examine VNTR stability again, 2 WSSV strains (PmTN4RU and LvAP11RU) with differing ORF94 tandem repeat numbers and slight differences in apparent virulence were passaged sequentially 6 times through black tiger shrimp Penaeus monodon, Indian white shrimp Feneropenaeus indicus or Pacific white leg shrimp Litopenaeus vannamei. PCR analyses to genotype the ORF94, ORF125 and ORF75 VNTRs did not identify any differences from either of the 2 parental WSSV strains after multiple passages through any of the shrimp species. These data were confirmed by sequence analysis and indicate that the stability of the genome regions containing these VNTRs is quite high at least for the WSSV strains, hosts and number of passages examined and that the VNTR sequences thus represent useful genetic markers for studying WSSV epidemiology.

Genetic variability in krill.

PubMed Central

Valentine, J W; Ayala, F J

1976-01-01

We have estimated genetic variability by gel electrophoresis in three species of krill, genus Euphausia (Arthropoda: Crustacea). Genetic variability is low where trophic resources are most seasonal, and high where trophic resources are most stable. Simlar trends have been found in benthic marine invertebrates. The observed trends of genetic variability do not correlate with trends in the stability of physical environment parameters. Images PMID:1061166

Is the Child "Father of the Man"? Evaluating the Stability of Genetic Influences across Development

ERIC Educational Resources Information Center

Ronald, Angelica

2011-01-01

This selective review considers findings in genetic research that have shed light on how genes operate across development. We will address the question of whether the child is "father of the Man" from a genetic perspective. In other words, do the same genetic influences affect the same traits across development? Using a "taster menu" approach and…

Genetic variability and evolutionary dynamics of viruses of the family Closteroviridae

PubMed Central

Rubio, Luis; Guerri, José; Moreno, Pedro

2013-01-01

RNA viruses have a great potential for genetic variation, rapid evolution and adaptation. Characterization of the genetic variation of viral populations provides relevant information on the processes involved in virus evolution and epidemiology and it is crucial for designing reliable diagnostic tools and developing efficient and durable disease control strategies. Here we performed an updated analysis of sequences available in Genbank and reviewed present knowledge on the genetic variability and evolutionary processes of viruses of the family Closteroviridae. Several factors have shaped the genetic structure and diversity of closteroviruses. (I) A strong negative selection seems to be responsible for the high genetic stability in space and time for some viruses. (2) Long distance migration, probably by human transport of infected propagative plant material, have caused that genetically similar virus isolates are found in distant geographical regions. (3) Recombination between divergent sequence variants have generated new genotypes and plays an important role for the evolution of some viruses of the family Closteroviridae. (4) Interaction between virus strains or between different viruses in mixed infections may alter accumulation of certain strains. (5) Host change or virus transmission by insect vectors induced changes in the viral population structure due to positive selection of sequence variants with higher fitness for host-virus or vector-virus interaction (adaptation) or by genetic drift due to random selection of sequence variants during the population bottleneck associated to the transmission process. PMID:23805130

Pathway-driven gene stability selection of two rheumatoid arthritis GWAS identifies and validates new susceptibility genes in receptor mediated signalling pathways.

PubMed

Eleftherohorinou, Hariklia; Hoggart, Clive J; Wright, Victoria J; Levin, Michael; Coin, Lachlan J M

2011-09-01

Rheumatoid arthritis (RA) is the commonest chronic, systemic, inflammatory disorder affecting ∼1% of the world population. It has a strong genetic component and a growing number of associated genes have been discovered in genome-wide association studies (GWAS), which nevertheless only account for 23% of the total genetic risk. We aimed to identify additional susceptibility loci through the analysis of GWAS in the context of biological function. We bridge the gap between pathway and gene-oriented analyses of GWAS, by introducing a pathway-driven gene stability-selection methodology that identifies potential causal genes in the top-associated disease pathways that may be driving the pathway association signals. We analysed the WTCCC and the NARAC studies of ∼5000 and ∼2000 subjects, respectively. We examined 700 pathways comprising ∼8000 genes. Ranking pathways by significance revealed that the NARAC top-ranked ∼6% laid within the top 10% of WTCCC. Gene selection on those pathways identified 58 genes in WTCCC and 61 in NARAC; 21 of those were common (P(overlap)< 10(-21)), of which 16 were novel discoveries. Among the identified genes, we validated 10 known RA associations in WTCCC and 13 in NARAC, not discovered using single-SNP approaches on the same data. Gene ontology functional enrichment analysis on the identified genes showed significant over-representation of signalling activity (P< 10(-29)) in both studies. Our findings suggest a novel model of RA genetic predisposition, which involves cell-membrane receptors and genes in second messenger signalling systems, in addition to genes that regulate immune responses, which have been the focus of interest previously.

Genetic Stability of Cognitive Development from Childhood to Adulthood.

ERIC Educational Resources Information Center

DeFries, J. C.; And Others

1987-01-01

A path model of genetic and family environmental transmission was fitted to published twin correlations and to general cognitive ability data from adoptive and nonadoptive families in which children were tested yearly through the fourth year. Longitudinal genetic correlations from infancy to adulthood were modeled explicitly, as were effects of…

Tracking the genetic stability of a honeybee breeding program with genetic markers

USDA-ARS?s Scientific Manuscript database

A genetic stock identification (GSI) assay was developed in 2008 to distinguish Russian honey bees from other honey bee stocks that are commercially produced in the United States. Probability of assignment (POA) values have been collected and maintained since the stock release in 2008 to the Russian...

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood

PubMed Central

Reichborn-Kjennerud, T.; Czajkowski, N.; Ystrøm, E.; Ørstavik, R.; Aggen, S. H.; Tambs, K.; Torgersen, S.; Neale, M. C.; Røysamb, E.; Krueger, R. F.; Knudsen, G. P.; Kendler, K. S.

2015-01-01

Background Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. Method DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. Results The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. Conclusion ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD. PMID:26050739

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood.

PubMed

Reichborn-Kjennerud, T; Czajkowski, N; Ystrøm, E; Ørstavik, R; Aggen, S H; Tambs, K; Torgersen, S; Neale, M C; Røysamb, E; Krueger, R F; Knudsen, G P; Kendler, K S

2015-10-01

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.

Identification of two key genes controlling chill haze stability of beer in barley (Hordeum vulgare L).

PubMed

Ye, Lingzhen; Huang, Yuqing; Dai, Fei; Ning, Huajiang; Li, Chengdao; Zhou, Meixue; Zhang, Guoping

2015-06-11

In bright beer, haze formation is a serious quality problem, degrading beer quality and reducing its shelf life. The quality of barley (Hordeum vulgare L) malt, as the main raw material for beer brewing, largely affects the colloidal stability of beer. In this study, the genetic mechanism of the factors affecting beer haze stability in barley was studied. Quantitative trait loci (QTL) analysis of alcohol chill haze (ACH) in beer was carried out using a Franklin/Yerong double haploid (DH) population. One QTL, named as qACH, was detected for ACH, and it was located on the position of about 108 cM in chromosome 4H and can explain about 20 % of the phenotypic variation. Two key haze active proteins, BATI-CMb and BATI-CMd were identified by proteomics analysis. Bioinformatics analysis showed that BATI-CMb and BATI-CMd had the same position as qACH in the chromosome. It may be deduced that BATI-CMb and BATI-CMd are candidate genes for qACH, controlling colloidal stability of beer. Polymorphism comparison between Yerong and Franklin in the nucleotide and amino acid sequence of BATI-CMb and BATI-CMd detected the corresponding gene specific markers, which could be used in marker-assisted selection for malt barley breeding. We identified a novel QTL, qACH controlling chill haze of beer, and two key haze active proteins, BATI-CMb and BATI-CMd. And further analysis showed that BATI-CMb and BATI-CMd might be the candidate genes associated with beer chill haze.

Genetics Home Reference: distal myopathy 2

MedlinePlus

... is unknown. This protein can attach to (bind) RNA, which is a chemical cousin of DNA. Some ... matrin 3 binds and stabilizes a type of RNA called messenger RNA (mRNA), which provides the genetic ...

Multi-Genetic Marker Approach and Spatio-Temporal Analysis Suggest There Is a Single Panmictic Population of Swordfish Xiphias gladius in the Indian Ocean

PubMed Central

Muths, Delphine; Le Couls, Sarah; Evano, Hugues; Grewe, Peter; Bourjea, Jerome

2013-01-01

Genetic population structure of swordfish Xiphias gladius was examined based on 2231 individual samples, collected mainly between 2009 and 2010, among three major sampling areas within the Indian Ocean (IO; twelve distinct sites), Atlantic (two sites) and Pacific (one site) Oceans using analysis of nineteen microsatellite loci (n = 2146) and mitochondrial ND2 sequences (n = 2001) data. Sample collection was stratified in time and space in order to investigate the stability of the genetic structure observed with a special focus on the South West Indian Ocean. Significant AMOVA variance was observed for both markers indicating genetic population subdivision was present between oceans. Overall value of F-statistics for ND2 sequences confirmed that Atlantic and Indian Oceans swordfish represent two distinct genetic stocks. Indo-Pacific differentiation was also significant but lower than that observed between Atlantic and Indian Oceans. However, microsatellite F-statistics failed to reveal structure even at the inter-oceanic scale, indicating that resolving power of our microsatellite loci was insufficient for detecting population subdivision. At the scale of the Indian Ocean, results obtained from both markers are consistent with swordfish belonging to a single unique panmictic population. Analyses partitioned by sampling area, season, or sex also failed to identify any clear structure within this ocean. Such large spatial and temporal homogeneity of genetic structure, observed for such a large highly mobile pelagic species, suggests as satisfactory to consider swordfish as a single panmictic population in the Indian Ocean. PMID:23717447

Advertisement call and genetic structure conservatism: good news for an endangered Neotropical frog

PubMed Central

Costa, William P.; Martins, Lucas B.; Nunes-de-Almeida, Carlos H. L.; Toledo, Luís Felipe

2016-01-01

Background: Many amphibian species are negatively affected by habitat change due to anthropogenic activities. Populations distributed over modified landscapes may be subject to local extinction or may be relegated to the remaining—likely isolated and possibly degraded—patches of available habitat. Isolation without gene flow could lead to variability in phenotypic traits owing to differences in local selective pressures such as environmental structure, microclimate, or site-specific species assemblages. Methods: Here, we tested the microevolution hypothesis by evaluating the acoustic parameters of 349 advertisement calls from 15 males from six populations of the endangered amphibian species Proceratophrys moratoi. In addition, we analyzed the genetic distances among populations and the genetic diversity with a haplotype network analysis. We performed cluster analysis on acoustic data based on the Bray-Curtis index of similarity, using the UPGMA method. We correlated acoustic dissimilarities (calculated by Euclidean distance) with geographical and genetic distances among populations. Results: Spectral traits of the advertisement call of P. moratoi presented lower coefficients of variation than did temporal traits, both within and among males. Cluster analyses placed individuals without congruence in population or geographical distance, but recovered the species topology in relation to sister species. The genetic distance among populations was low; it did not exceed 0.4% for the most distant populations, and was not correlated with acoustic distance. Discussion: Both acoustic features and genetic sequences are highly conserved, suggesting that populations could be connected by recent migrations, and that they are subject to stabilizing selective forces. Although further studies are required, these findings add to a growing body of literature suggesting that this species would be a good candidate for a reintroduction program without negative effects on communication or genetic impact. PMID:27190717

From Mendel's discovery on pea to today's plant genetics and breeding : Commemorating the 150th anniversary of the reading of Mendel's discovery.

PubMed

Smýkal, Petr; K Varshney, Rajeev; K Singh, Vikas; Coyne, Clarice J; Domoney, Claire; Kejnovský, Eduard; Warkentin, Thomas

2016-12-01

This work discusses several selected topics of plant genetics and breeding in relation to the 150th anniversary of the seminal work of Gregor Johann Mendel. In 2015, we celebrated the 150th anniversary of the presentation of the seminal work of Gregor Johann Mendel. While Darwin's theory of evolution was based on differential survival and differential reproductive success, Mendel's theory of heredity relies on equality and stability throughout all stages of the life cycle. Darwin's concepts were continuous variation and "soft" heredity; Mendel espoused discontinuous variation and "hard" heredity. Thus, the combination of Mendelian genetics with Darwin's theory of natural selection was the process that resulted in the modern synthesis of evolutionary biology. Although biology, genetics, and genomics have been revolutionized in recent years, modern genetics will forever rely on simple principles founded on pea breeding using seven single gene characters. Purposeful use of mutants to study gene function is one of the essential tools of modern genetics. Today, over 100 plant species genomes have been sequenced. Mapping populations and their use in segregation of molecular markers and marker-trait association to map and isolate genes, were developed on the basis of Mendel's work. Genome-wide or genomic selection is a recent approach for the development of improved breeding lines. The analysis of complex traits has been enhanced by high-throughput phenotyping and developments in statistical and modeling methods for the analysis of phenotypic data. Introgression of novel alleles from landraces and wild relatives widens genetic diversity and improves traits; transgenic methodologies allow for the introduction of novel genes from diverse sources, and gene editing approaches offer possibilities to manipulate gene in a precise manner.

Advertisement call and genetic structure conservatism: good news for an endangered Neotropical frog.

PubMed

Forti, Lucas R; Costa, William P; Martins, Lucas B; Nunes-de-Almeida, Carlos H L; Toledo, Luís Felipe

2016-01-01

Many amphibian species are negatively affected by habitat change due to anthropogenic activities. Populations distributed over modified landscapes may be subject to local extinction or may be relegated to the remaining-likely isolated and possibly degraded-patches of available habitat. Isolation without gene flow could lead to variability in phenotypic traits owing to differences in local selective pressures such as environmental structure, microclimate, or site-specific species assemblages. Here, we tested the microevolution hypothesis by evaluating the acoustic parameters of 349 advertisement calls from 15 males from six populations of the endangered amphibian species Proceratophrys moratoi. In addition, we analyzed the genetic distances among populations and the genetic diversity with a haplotype network analysis. We performed cluster analysis on acoustic data based on the Bray-Curtis index of similarity, using the UPGMA method. We correlated acoustic dissimilarities (calculated by Euclidean distance) with geographical and genetic distances among populations. Spectral traits of the advertisement call of P. moratoi presented lower coefficients of variation than did temporal traits, both within and among males. Cluster analyses placed individuals without congruence in population or geographical distance, but recovered the species topology in relation to sister species. The genetic distance among populations was low; it did not exceed 0.4% for the most distant populations, and was not correlated with acoustic distance. Both acoustic features and genetic sequences are highly conserved, suggesting that populations could be connected by recent migrations, and that they are subject to stabilizing selective forces. Although further studies are required, these findings add to a growing body of literature suggesting that this species would be a good candidate for a reintroduction program without negative effects on communication or genetic impact.

Graphene Sheets Stabilized on Genetically Engineered M13 Viral Templates as Conducting Frameworks for Hybrid Energy-Storage Materials

DTIC Science & Technology

2012-01-01

Hammond, A. M. Belcher, Nat. Nanotechnol. 2011. [19] C. F. Barbass III, D. R. Burton, J. K. Scott, G. J. Silverman, Phage display : a laboratory manual...with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...19b. TELEPHONE NUMBER (Include area code) New Reprint Graphene Sheets Stabilized on Genetically Engineered M13 Viral Templates as Conducting

Genetic stability of ectomycorrhizal fungi is not affected by cryopreservation at -130 °C or cold storage with repeated sub-cultivations over a period of 2 years.

PubMed

Crahay, Charlotte; Munaut, Françoise; Colpaert, Jan V; Huret, Stéphanie; Declerck, Stéphane

2017-08-01

Cryopreservation is considered the most reliable method for storage of filamentous fungi including ectomycorrhizal (ECM) fungi. A number of studies, however, have reported genetic changes in fungus cultures following cryopreservation. In the present study, the genetic stability of six ECM fungus isolates was analyzed using amplified fragment length polymorphism (AFLP). The isolates were preserved for 2 years either by cryopreservation (at -130 °C) or by storage at 4 °C with regular sub-cultivation. A third preservation treatment consisting of isolates maintained on Petri dishes at 22-23 °C for 2 years (i.e., without any sub-cultivation) was included and used as a control. The differences observed in AFLP patterns between the three preservation methods remained within the range of the total error generated by the AFLP procedure (6.85%). Therefore, cryopreservation at -130 °C and cold storage with regular sub-cultivation did not affect the genetic stability of the ECM fungus isolates, and both methods can be used for the routine storage of ECM fungus isolates over a period of 2 years.

A Bayesian phylogenetic approach to estimating the stability of linguistic features and the genetic biasing of tone.

PubMed

Dediu, Dan

2011-02-07

Language is a hallmark of our species and understanding linguistic diversity is an area of major interest. Genetic factors influencing the cultural transmission of language provide a powerful and elegant explanation for aspects of the present day linguistic diversity and a window into the emergence and evolution of language. In particular, it has recently been proposed that linguistic tone-the usage of voice pitch to convey lexical and grammatical meaning-is biased by two genes involved in brain growth and development, ASPM and Microcephalin. This hypothesis predicts that tone is a stable characteristic of language because of its 'genetic anchoring'. The present paper tests this prediction using a Bayesian phylogenetic framework applied to a large set of linguistic features and language families, using multiple software implementations, data codings, stability estimations, linguistic classifications and outgroup choices. The results of these different methods and datasets show a large agreement, suggesting that this approach produces reliable estimates of the stability of linguistic data. Moreover, linguistic tone is found to be stable across methods and datasets, providing suggestive support for the hypothesis of genetic influences on its distribution.

Genetic and Environmental Architecture of Changes in Episodic Memory from Middle to Late Middle Age

PubMed Central

Panizzon, Matthew S.; Neale, Michael C.; Docherty, Anna R.; Franz, Carol E.; Jacobson, Kristen C.; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K.; McKenzie, Ruth M.; Lyons, Michael J.; Kremen, William S.

2015-01-01

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined six measures from three episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints two of three test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for one test-specific factor (list learning). Mean change over time was nonsignificant for one test-level factor; one declined; one improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. PMID:25938244

Genetic and environmental architecture of changes in episodic memory from middle to late middle age.

PubMed

Panizzon, Matthew S; Neale, Michael C; Docherty, Anna R; Franz, Carol E; Jacobson, Kristen C; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K; McKenzie, Ruth; Lyons, Michael J; Kremen, William S

2015-06-01

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined 6 measures from 3 episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints 2 of 3 test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for 1 test-specific factor (list learning). Mean change over time was nonsignificant for 1 test-level factor; 1 declined; 1 improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. (c) 2015 APA, all rights reserved.

Word Reading and Reading Comprehension: Stability, Overlap and Independence

ERIC Educational Resources Information Center

Betjemann, Rebecca S.; Willcutt, Erik G.; Olson, Richard K.; Keenan, Janice M.; Defries, John C.; Wadsworth, Sally J.

2008-01-01

Longitudinal twin data were analyzed to investigate the etiology of the stability of genetic and environmental influences on word reading and reading comprehension, as well as the stability of those influences on their relationship. Participating twin pairs were initially tested at a mean age of 10.3 years, and retested approximately five years…

A longitudinal, population-based twin study of avoidant and obsessive-compulsive personality disorder traits from early to middle adulthood

PubMed Central

Gjerde, L. C.; Czajkowski, N.; Røysamb, E.; Ystrom, E.; Tambs, K.; Aggen, S. H.; Ørstavik, R. E.; Kendler, K. S.; Reichborn-Kjennerud, T.; Knudsen, G. P.

2015-01-01

Background The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability. Method AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits. Results For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2. Conclusion Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes. PMID:26273730

A longitudinal, population-based twin study of avoidant and obsessive-compulsive personality disorder traits from early to middle adulthood.

PubMed

Gjerde, L C; Czajkowski, N; Røysamb, E; Ystrom, E; Tambs, K; Aggen, S H; Ørstavik, R E; Kendler, K S; Reichborn-Kjennerud, T; Knudsen, G P

2015-12-01

The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability. AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits. For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2. Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes.

A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait

PubMed Central

Geroldinger, Ludwig; Bürger, Reinhard

2014-01-01

The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. PMID:24726489

A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait.

PubMed

Geroldinger, Ludwig; Bürger, Reinhard

2014-06-01

The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

In vivo quantitative analysis of Talin turnover in response to force

PubMed Central

Hákonardóttir, Guðlaug Katrín; López-Ceballos, Pablo; Herrera-Reyes, Alejandra Donají; Das, Raibatak; Coombs, Daniel; Tanentzapf, Guy

2015-01-01

Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell–ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how integrin-based adhesions respond to increased and decreased mechanical forces. A critical means of regulating integrin-based adhesion is provided by modulating the turnover of integrin and its adhesion complex (integrin adhesion complex [IAC]). The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluorescence recovery after photobleaching. Experiments were carried out in live, intact flies in genetic backgrounds that increased or decreased the force applied on sites of adhesion. This analysis showed that when force is elevated, the rate of assembly of new adhesions increases such that cell–ECM adhesion is stabilized. Moreover, under conditions of decreased force, the overall rate of turnover, but not the proportion of adhesion complex components undergoing turnover, increases. Using point mutations, we identify the key functional domains of Talin that mediate its response to force. Finally, by fitting a mathematical model to the data, we uncover the mechanisms that mediate the stabilization of ECM-based adhesion during development. PMID:26446844

Vascular Health and Genetic Risk Affect Mild Cognitive Impairment Status and 4-Year Stability: Evidence From the Victoria Longitudinal Study

PubMed Central

MacDonald, Stuart W. S.; Vergote, David; Jhamandas, Jack; Westaway, David; Dixon, Roger A.

2016-01-01

Objectives: Mild cognitive impairment (MCI) is a high-risk condition for progression to Alzheimer’s disease (AD). Vascular health is a key mechanism underlying age-related cognitive decline and neurodegeneration. AD-related genetic risk factors may be associated with preclinical cognitive status changes. We examine independent and cross-domain interactive effects of vascular and genetic markers for predicting MCI status and stability. Method: We used cross-sectional and 2-wave longitudinal data from the Victoria Longitudinal Study, including indicators of vascular health (e.g., reported vascular diseases, measured lung capacity and pulse rate) and genetic risk factors—that is, apolipoprotein E (APOE; rs429358 and rs7412; the presence vs absence of ε4) and catechol-O-methyltransferase (COMT; rs4680; met/met vs val/val). We examined associations with objectively classified (a) cognitive status at baseline (not impaired congnitive (NIC) controls vs MCI) and (b) stability or transition of cognitive status across a 4-year interval (stable NIC–NIC vs chronic MCI–MCI or transitional NIC–MCI). Results: Using logistic regression, indicators of vascular health, both independently and interactively with APOE ε4, were associated with risk of MCI at baseline and/or associated with MCI conversion or MCI stability over the retest interval. Discussion: Several vascular health markers of aging predict MCI risk. Interactively, APOE ε4 may intensify the vascular health risk for MCI. PMID:26362601

Colombian forensic genetics as a form of public science: The role of race, nation and common sense in the stabilization of DNA populations.

PubMed

Schwartz-Marín, Ernesto; Wade, Peter; Cruz-Santiago, Arely; Cárdenas, Roosbelinda

2015-12-01

Abstract This article examines the role that vernacular notions of racialized-regional difference play in the constitution and stabilization of DNA populations in Colombian forensic science, in what we frame as a process of public science. In public science, the imaginations of the scientific world and common-sense public knowledge are integral to the production and circulation of science itself. We explore the origins and circulation of a scientific object--'La Tabla', published in Paredes et al. and used in genetic forensic identification procedures--among genetic research institutes, forensic genetics laboratories and courtrooms in Bogotá. We unveil the double life of this central object of forensic genetics. On the one hand, La Tabla enjoys an indisputable public place in the processing of forensic genetic evidence in Colombia (paternity cases, identification of bodies, etc.). On the other hand, the relations it establishes between 'race', geography and genetics are questioned among population geneticists in Colombia. Although forensic technicians are aware of the disputes among population geneticists, they use and endorse the relations established between genetics, 'race' and geography because these fit with common-sense notions of visible bodily difference and the regionalization of race in the Colombian nation.

Colombian forensic genetics as a form of public science: The role of race, nation and common sense in the stabilization of DNA populations

PubMed Central

Schwartz-Marín, Ernesto; Wade, Peter; Cruz-Santiago, Arely; Cárdenas, Roosbelinda

2015-01-01

This article examines the role that vernacular notions of racialized-regional difference play in the constitution and stabilization of DNA populations in Colombian forensic science, in what we frame as a process of public science. In public science, the imaginations of the scientific world and common-sense public knowledge are integral to the production and circulation of science itself. We explore the origins and circulation of a scientific object – ‘La Tabla’, published in Paredes et al. and used in genetic forensic identification procedures – among genetic research institutes, forensic genetics laboratories and courtrooms in Bogotá. We unveil the double life of this central object of forensic genetics. On the one hand, La Tabla enjoys an indisputable public place in the processing of forensic genetic evidence in Colombia (paternity cases, identification of bodies, etc.). On the other hand, the relations it establishes between ‘race’, geography and genetics are questioned among population geneticists in Colombia. Although forensic technicians are aware of the disputes among population geneticists, they use and endorse the relations established between genetics, ‘race’ and geography because these fit with common-sense notions of visible bodily difference and the regionalization of race in the Colombian nation. PMID:27480000

Tumor Hypoxia and Genetic Alterations in Sporadic Cancers

PubMed Central

Koi, Minoru; Boland, C.R.

2011-01-01

The cancer genome contains many gene alterations. How cancer cells acquire these alterations is a matter for discussion. One hypothesis is that cancer cells obtain mutations in genome stability genes at an early stage of tumor development, which results in genetic instability and generates a gene pool that enhances cellular proliferation and survival. Another hypothesis puts its emphasis on the natural selection of gene mutations for fitness. Recent data for systematic cancer genome sequencing shows that mutations in stability genes are rare in human sporadic cancers. Instead, many “passenger” mutations that do not drive the carcinogenesis process have been found in the cancer genome. Both the hypotheses mentioned above fall short in explaining recent data. Recently, many studies demonstrate the role of the tumor microenvironment, especially hypoxia and reoxygenation, in genetic instability. In this review, literature will be presented which supports a third hypothesis, i.e. that hypoxia/re-oxygenation induces genetic instability. PMID:21272156

Looking at the stability of life-support microorganisms in space : the MELGEN activity highlights the cyanobacterium Arthrospira sp. PCC8005

NASA Astrophysics Data System (ADS)

Morin, Nicolas

The MELGEN activity (MELiSSA Genetic Stability Study) mainly covers the molecular aspects of the regenerative life-support system MELiSSA (Micro-Ecological Life Support System Alternative) of the European Space Agency (ESA). The general objective of MELGEN is to establish and validate methods and the related hardware in order to detect genetic instability and microbial contaminants in the MELISSA compartments. This includes (1) a genetic description of the MELISSA strains, (2) studies of microbial behavior and genetic stability in bioreactors and (3) the detection of chemical, genetical and biological contamination and their effect on microbial metabolism. Selected as oxygen producer and complementary food source, the cyanobacterium Arthrospira sp. PCC8005 plays a major role within the MELiSSA loop. As the genomic information on this organism was insufficient, sequencing of its genome was proposed at the French National Sequencing Center, Genoscope, as a joint effort between ESA and different laboratories. So far, a preliminary assembly of 16 contigs representing circa 6.3 million basepairs was obtained. Even though the finishing of the genome is on its way, automatic annotation of the contigs has already been performed on the MaGe annotation platform, and curation of the sequence is currently being carried out, with a special focus on biosynthesis pathways, photosynthesis, and maintenance processes of the cell. According to the index of repetitiveness described by Haubold and Wiehe (2006), we discovered that the genome of Arthrospira sp. is among the 50 most repeated bacterial genomes sequenced to date. Thanks to the sequencing project, we have identified and catalogued mobile genetics elements (MGEs) dispersed throughout the unique chromosome of this cyanobacterium. They represent a quite large proportion of the genome, as genes identified as putative transposases are indeed found in circa 5 Results : We currently have a first draft of the complete genome of Arthrospira sp. PCC 8005, fully annotated. This genomic information opens the gates to a better understanding of the biology of this cyanobacterium and will be a key to the development of appropriate derivatives that provide enhanced performances (e.g. radiation resistance, genetic stability, photosynthesis and nutritive properties).

Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

NASA Astrophysics Data System (ADS)

Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

2017-04-01

Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main coniferous species for a sustainable forest management in the context of climate change), financed by the Executive Agency for Higher Education, Research, Development and Innovation Funding, grant number PN-II-PC-PCCA-2013-4-0695.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

PubMed Central

Patten, Shunmoogum A.; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary A.B.; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J. Alexander

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease. PMID:29202456

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

PubMed

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

A field release of genetically engineered gypsy moth (Lymantria dispar L.) Nuclear Polyhedrosis Virus (LdNPV)

Treesearch

Vincent D' Amico; Joseph S. Elkinton; John D. Podgwaite; James M. Slavicek; Michael L. McManus; John P. Burand

1999-01-01

The gypsy moth (Lymantria dispar L.) nuclear polyhedrosis virus was genetically engineered for nonpersistence by removal of the gene coding for polyhedrin production and stabilized using a coocclusion process. A β-galactosidase marker gene was inserted into the genetically engineered virus (LdGEV) so that infected larvae could be tested for...

The Design of Power System Stability Controller Based on the PCH Theory and Improved Genetic Algorithm

NASA Astrophysics Data System (ADS)

Liu, Zhijian; Yin, Donghui; Yan, Jun

2017-05-01

Low frequency oscillation is still frequently happened in the power system and it affects the safety and stability of power system directly. With the continuously expending of the interconnection scale of power grid, the risk of low frequency oscillation becomes more and more noticeable. Firstly, the basic theory of port-controlled Hamilton (PCH) and its application is analyzed. Secondly, based on the PCH theory and the dynamic model of system, from the viewpoint of energy, the nonlinear stability controller of power system is designed. By the improved genetic algorithm, the parameters of the PCH model are optimized. Finally, a simulation model with PCH is built to vary the effectiveness of the method proposed in this paper.

Chromosomal Rearrangements in Salmonella enterica Serotype Typhi Affecting Molecular Typing in Outbreak Investigations

PubMed Central

Echeita, M. A.; Usera, M. A.

1998-01-01

Salmonella enterica serotype Typhi strains belonging to eight different outbreaks of typhoid fever that occurred in Spain between 1989 and 1994 were analyzed by ribotyping and pulsed-field gel electrophoresis. For three outbreaks, two different patterns were detected for each outbreak. The partial digestion analysis by the intron-encoded endonuclease I-CeuI of the two different strains from each outbreak provided an excellent tool for examining the organization of the genomes of epidemiologically related strains. S. enterica serotype Typhi seems to be more susceptible than other serotypes to genetic rearrangements produced by homologous recombinations between rrn operons; these rearrangements do not substantially alter the stability or survival of the bacterium. We conclude that genetic rearrangements can occur during the emergence of an outbreak. PMID:9650981

Could refuge theory and rivers acting as barriers explain the genetic variability distribution in the Atlantic Forest?

PubMed

Cazé, Ana Luiza R; Mäder, Geraldo; Nunes, Teonildes S; Queiroz, Luciano P; de Oliveira, Guilherme; Diniz-Filho, José Alexandre F; Bonatto, Sandro L; Freitas, Loreta B

2016-08-01

The Atlantic Forest is one of the most species-rich ecoregions in the world. The historical origins of this richness and the evolutionary processes that produced diversification and promoted speciation in this ecosystem remain poorly understood. In this context, focusing on Passiflora contracta, an endemic species from the Atlantic Forest distributed exclusively at sea level along forest edges, this study aimed to characterize the patterns of genetic variability and explore two hypotheses that attempt to explain the possible causes of the genetic diversity in this region: the refuge and riverine barrier theories. We employed Bayesian methods combined with niche modeling to identify genetically homogeneous groups, to determine the diversification age, and identify long-term climate stability areas to species survival. The analyses were performed using molecular markers from nuclear and plastid genomes, with samples collected throughout the entire geographic distribution of the species, and comparisons with congeners species. The results indicated that populations were genetically structured and provided evidence of demographic stability. The molecular markers indicated the existence of a clear structure and the presence of five homogeneous groups. Interestingly, the separation of the groups coincides with the geographical locations of local rivers, corroborating the hypothesis of rivers acting as barriers to gene flow in this species. The highest levels of genetic diversity and the areas identified as having long-term climate stability were found in the same region reported for other species as a possible refuge area during the climatic changes of the Quaternary. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic control of ColE1 plasmid stability that is independent of plasmid copy number regulation.

PubMed

Standley, Melissa S; Million-Weaver, Samuel; Alexander, David L; Hu, Shuai; Camps, Manel

2018-06-16

ColE1-like plasmid vectors are widely used for expression of recombinant genes in E. coli. For these vectors, segregation of individual plasmids into daughter cells during cell division appears to be random, making them susceptible to loss over time when no mechanisms ensuring their maintenance are present. Here we use the plasmid pGFPuv in a recA relA strain as a sensitized model to study factors affecting plasmid stability in the context of recombinant gene expression. We find that in this model, plasmid stability can be restored by two types of genetic modifications to the plasmid origin of replication (ori) sequence: point mutations and a novel 269 nt duplication at the 5' end of the plasmid ori, which we named DAS (duplicated anti-sense) ori. Combinations of these modifications produce a range of copy numbers and of levels of recombinant expression. In direct contradiction with the classic random distribution model, we find no correlation between increased plasmid copy number and increased plasmid stability. Increased stability cannot be explained by reduced levels of recombinant gene expression either. Our observations would be more compatible with a hybrid clustered and free-distribution model, which has been recently proposed based on detection of individual plasmids in vivo using super-resolution fluorescence microscopy. This work suggests a role for the plasmid ori in the control of segregation of ColE1 plasmids that is distinct from replication initiation, opening the door for the genetic regulation of plasmid stability as a strategy aimed at enhancing large-scale recombinant gene expression or bioremediation.

The G matrix under fluctuating correlational mutation and selection.

PubMed

Revell, Liam J

2007-08-01

Theoretical quantitative genetics provides a framework for reconstructing past selection and predicting future patterns of phenotypic differentiation. However, the usefulness of the equations of quantitative genetics for evolutionary inference relies on the evolutionary stability of the additive genetic variance-covariance matrix (G matrix). A fruitful new approach for exploring the evolutionary dynamics of G involves the use of individual-based computer simulations. Previous studies have focused on the evolution of the eigenstructure of G. An alternative approach employed in this paper uses the multivariate response-to-selection equation to evaluate the stability of G. In this approach, I measure similarity by the correlation between response-to-selection vectors due to random selection gradients. I analyze the dynamics of G under several conditions of correlational mutation and selection. As found in a previous study, the eigenstructure of G is stabilized by correlational mutation and selection. However, over broad conditions, instability of G did not result in a decreased consistency of the response to selection. I also analyze the stability of G when the correlation coefficients of correlational mutation and selection and the effective population size change through time. To my knowledge, no prior study has used computer simulations to investigate the stability of G when correlational mutation and selection fluctuate. Under these conditions, the eigenstructure of G is unstable under some simulation conditions. Different results are obtained if G matrix stability is assessed by eigenanalysis or by the response to random selection gradients. In this case, the response to selection is most consistent when certain aspects of the eigenstructure of G are least stable and vice versa.

Single-neuron labeling with inducible cre-mediated knockout in transgenic mice

PubMed Central

Young, Paul; Qiu, Li; Wang, Dongqing; Zhao, Shengli; Gross, James; Feng, Guoping

2011-01-01

To facilitate functional analysis of neuronal connectivity in a mammalian nervous system tightly packed with billions of cells, we developed a new technique that allows inducible genetic manipulations within fluorescently labeled single neurons in mice. We term this technique SLICK for Single-neuron Labeling with Inducible Cre-mediated Knockout. SLICK is achieved by co-expressing a drug-inducible form of cre recombinase and a fluorescent protein within the same small subsets of neurons. Thus, SLICK combines the powerful cre recombinase system for conditional genetic manipulation and the fluorescent labeling of single neurons for imaging. We demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we apply SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals. More broadly, these studies demonstrate a cre-LoxP compatible system for dissecting gene functions in single identifiable neurons. PMID:18454144

A novel missense NDP mutation [p.(Cys93Arg)] with a manifesting carrier in an austrian family with Norrie disease.

PubMed

Parzefall, Thomas; Lucas, Trevor; Ritter, Markus; Ludwig, Martin; Ramsebner, Reinhard; Frohne, Alexandra; Schöfer, Christian; Hengstschläger, Markus; Frei, Klemens

2014-01-01

Norrie disease is a rare, X-linked genetic syndrome characterized by combined congenital blindness and progressive hearing impairment. Norrie disease is caused by alterations in the NDP gene encoding the growth factor norrin that plays a key role in vascular development and stabilization of the eye, inner ear and brain. We identified a family with 3 affected deafblind males and a single female carrier presenting with a serous retinal detachment but normal hearing. Genetic analysis revealed a novel c.277T>C missense mutation causing the substitution of a hydrophobic cysteine to a hydrophilic arginine [p.(Cys93Arg)] within the highly conserved cysteine knot domain of the norrin protein. These results should expand the scope for amniocentesis and genetic testing for Norrie disease which is gaining in importance due to novel postnatal therapeutic concepts to alleviate the devastating retinal symptoms of Norrie disease. © 2014 S. Karger AG, Basel.

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem cells

PubMed Central

Luo, Lan; Kawakatsu, Miho; Guo, Chao-Wan; Urata, Yoshishige; Huang, Wen-Jing; Ali, Haytham; Doi, Hanako; Kitajima, Yuriko; Tanaka, Takayuki; Goto, Shinji; Ono, Yusuke; Xin, Hong-Bo; Hamano, Kimikazu; Li, Tao-Sheng

2014-01-01

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem (iPS) cells were investigated with two human iPS cell lines (201B7 and 253G1). Cells used in this study were expanded from a single colony of each cell line with the addition of proprietary antioxidant supplement or homemade antioxidant cocktail in medium, and maintained in parallel for 2 months. The cells grew well in all culture conditions and kept “stemness”. Although antioxidants modestly decreased the levels of intracellular reactive oxygen species, there were no differences in the expression of 53BP1 and pATM, two critical molecules related with DNA damage and repair, under various culture conditions. CGH analysis showed that the events of genetic aberrations were decreased only in the 253G1 iPS cells with the addition of homemade antioxidant cocktail. Long-term culture will be necessary to confirm whether low dose antioxidants improve the quality and genomic stability of iPS cells. PMID:24445363

Exploring and Harnessing Haplotype Diversity to Improve Yield Stability in Crops.

PubMed

Qian, Lunwen; Hickey, Lee T; Stahl, Andreas; Werner, Christian R; Hayes, Ben; Snowdon, Rod J; Voss-Fels, Kai P

2017-01-01

In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches. These include highly detailed assessment of population structure and genotypic diversity, facilitating the identification of selective sweeps and signatures of directional selection, dissection of genetic variants that underlie important agronomic traits, and genomic selection (GS) strategies that not only consider major-effect genes. Single-nucleotide polymorphism (SNP) markers today represent the genotyping system of choice for crop genetic studies because they occur abundantly in plant genomes and are easy to detect. SNPs are typically biallelic, however, hence their information content compared to multiallelic markers is low, limiting the resolution at which SNP-trait relationships can be delineated. An efficient way to overcome this limitation is to construct haplotypes based on linkage disequilibrium, one of the most important features influencing genetic analyses of crop genomes. Here, we give an overview of the latest advances in genomics-based haplotype analyses in crops, highlighting their importance in the context of polyploidy and genome evolution, linkage drag, and co-selection. We provide examples of how haplotype analyses can complement well-established quantitative genetics frameworks, such as quantitative trait analysis and GS, ultimately providing an effective tool to equip modern crops with environment-tailored characteristics.

African Swine Fever Virus NP868R Capping Enzyme Promotes Reovirus Rescue during Reverse Genetics by Promoting Reovirus Protein Expression, Virion Assembly, and RNA Incorporation into Infectious Virions

PubMed Central

Eaton, Heather E.; Kobayashi, Takeshi; Dermody, Terence S.; Johnston, Randal N.

2017-01-01

ABSTRACT Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5′ nucleotide of mRNA. The traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme during reovirus rescue. C3P3, a fusion protein containing T7 RNA polymerase and NP868R, was found to increase protein expression 5- to 10-fold compared to T7 RNA polymerase alone while enhancing reovirus rescue from the current reverse genetics system by 100-fold. Surprisingly, RNA stability was not increased by C3P3, suggesting a direct effect on protein translation. A time course analysis revealed that C3P3 increased protein synthesis within the first 2 days of a reverse genetics transfection. This analysis also revealed that C3P3 enhanced processing of outer capsid μ1 protein to μ1C, a previously described hallmark of reovirus assembly. Finally, to determine the rate of infectious-RNA incorporation into new virions, we developed a new recombinant reovirus S1 gene that expressed the fluorescent protein UnaG. Following transfection of cells with UnaG and infection with wild-type virus, passage of UnaG through progeny was significantly enhanced by C3P3. These data suggest that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation. IMPORTANCE Our findings expand our understanding of how viruses utilize capping, suggesting that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation, in addition to enhancing protein translation. Beyond providing mechanistic insight into reovirus replication, our findings also show that reovirus reverse genetics rescue is enhanced 100-fold by the NP868R capping enzyme. Since reovirus shows promise as a cancer therapy, efficient reovirus reverse genetics rescue will accelerate production of recombinant reoviruses as candidates to enhance therapeutic potency. NP868R-assisted reovirus rescue will also expedite production of recombinant reovirus for mechanistic insights into reovirus protein function and structure. PMID:28298603

Certification of reference materials for detection of the human prothrombin gene G20210A sequence variant.

PubMed

Gancberg, David; Corbisier, Philippe; Meeus, Nele; Marki-Zay, Janos; Mannhalter, Christine; Schimmel, Heinz

2008-01-01

There is a need for reference materials (RMs) in the field of genetic testing for verification of test results obtained in patients and probands. For the frequent genetic variation G20210A in the prothrombin gene, it has been shown that purified plasmids containing the gene fragment harbouring the mutation constitute good candidate RMs. Plasmid-type RMs were characterised for homogeneity, stability, sequence identity and fitness for purpose. Their certification required the use of different real-time PCR methods for genotyping and quantification of the plasmid copy number. Homogeneity, stability and fitness for the purpose of the plasmids could be demonstrated. The long-term stability (up to 24 months) of the materials was confirmed by highly sensitive and specific quantitative real-time PCR methods. New types of certified RMs (CRMs) for genetic testing of the human prothrombin gene G20210A sequence variant are available. Their fitness for purpose was demonstrated and no evidence was found that they would not work with other methods as long as these are targeting the whole or parts of the prothrombin gene fragment inserted into the plasmids. The described CRMs support the efforts of the international community in development, validation and harmonisation of tests for molecular genetic testing.

Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

PubMed

Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

2015-03-01

Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

Mixed models for selection of Jatropha progenies with high adaptability and yield stability in Brazilian regions.

PubMed

Teodoro, P E; Bhering, L L; Costa, R D; Rocha, R B; Laviola, B G

2016-08-19

The aim of this study was to estimate genetic parameters via mixed models and simultaneously to select Jatropha progenies grown in three regions of Brazil that meet high adaptability and stability. From a previous phenotypic selection, three progeny tests were installed in 2008 in the municipalities of Planaltina-DF (Midwest), Nova Porteirinha-MG (Southeast), and Pelotas-RS (South). We evaluated 18 families of half-sib in a randomized block design with three replications. Genetic parameters were estimated using restricted maximum likelihood/best linear unbiased prediction. Selection was based on the harmonic mean of the relative performance of genetic values method in three strategies considering: 1) performance in each environment (with interaction effect); 2) performance in each environment (with interaction effect); and 3) simultaneous selection for grain yield, stability and adaptability. Accuracy obtained (91%) reveals excellent experimental quality and consequently safety and credibility in the selection of superior progenies for grain yield. The gain with the selection of the best five progenies was more than 20%, regardless of the selection strategy. Thus, based on the three selection strategies used in this study, the progenies 4, 11, and 3 (selected in all environments and the mean environment and by adaptability and phenotypic stability methods) are the most suitable for growing in the three regions evaluated.

Genetic and Environmental Influences on the Development and Stability of Executive Functions in Children of Preschool Age: A Longitudinal Study of Japanese Twins

ERIC Educational Resources Information Center

Fujisawa, Keiko K.; Todo, Naoya; Ando, Juko

2017-01-01

Executive functions (EF) are an important predictor of later adaptive development. A number of environmental influences, such as parenting, have been suggested as important promoters of EF development. However, behavioural genetic research has demonstrated that many environmental influences could be affected by genetic influences. Therefore, it is…

Changes in the genetic diversity of eastern hemlock as a result of different forest management practices

Treesearch

Gary J. Hawley; Donald H. DeHayes; John C. Brissette

2000-01-01

Loss of populations and individuals within species to human-induced selective forces can result in loss of specific genes and overall genetic diversity upon which productivity, ecosystem stability, long-term survival, and evolution depend. This is particularly true for long-lived organisms, such as forest trees, because genetic diversity confers adaptability necessary...

Effect of genetic background on the stability of sunflower fatty acid composition in different high oleic mutations.

PubMed

Alberio, Constanza; Aguirrezábal, Luis An; Izquierdo, Natalia G; Reid, Roberto; Zuil, Sebastián; Zambelli, Andrés

2018-02-01

The effect of genetic background on the stability of fatty acid composition in sunflower near isogenic lines (NILs) carrying high-oleic Pervenets (P) or high-oleic NM1 mutations was studied. The materials were field-tested in different locations and at different sowing dates to evaluate a wide range of environmental conditions. Relationships were established between the fatty acids and the minimum night temperature (MNT) and the response was characterized. A genetic background effect for the fatty acid composition was found in both groups of NILs. The NM1-NILs showed an oleic level higher than 910 g kg -1 and they were more stable across environments with a zero or low dependence on the genetic background; on the other hand, high oleic materials bearing the P mutation showed lower levels of oleic acid, with a higher variation in fatty acid composition and a highly significant dependence on the genetic background. The NM1 mutation is the best option to develop ultra-high oleic sunflower oil that is stable across environments and genetic backgrounds, making its agronomical production more efficient and predictable. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Vascular Health and Genetic Risk Affect Mild Cognitive Impairment Status and 4-Year Stability: Evidence From the Victoria Longitudinal Study.

PubMed

DeCarlo, Correne A; MacDonald, Stuart W S; Vergote, David; Jhamandas, Jack; Westaway, David; Dixon, Roger A

2016-11-01

Mild cognitive impairment (MCI) is a high-risk condition for progression to Alzheimer's disease (AD). Vascular health is a key mechanism underlying age-related cognitive decline and neurodegeneration. AD-related genetic risk factors may be associated with preclinical cognitive status changes. We examine independent and cross-domain interactive effects of vascular and genetic markers for predicting MCI status and stability. We used cross-sectional and 2-wave longitudinal data from the Victoria Longitudinal Study, including indicators of vascular health (e.g., reported vascular diseases, measured lung capacity and pulse rate) and genetic risk factors-that is, apolipoprotein E (APOE; rs429358 and rs7412; the presence vs absence of ε4) and catechol-O-methyltransferase (COMT; rs4680; met/met vs val/val). We examined associations with objectively classified (a) cognitive status at baseline (not impaired congnitive (NIC) controls vs MCI) and (b) stability or transition of cognitive status across a 4-year interval (stable NIC-NIC vs chronic MCI-MCI or transitional NIC-MCI). Using logistic regression, indicators of vascular health, both independently and interactively with APOE ε4, were associated with risk of MCI at baseline and/or associated with MCI conversion or MCI stability over the retest interval. Several vascular health markers of aging predict MCI risk. Interactively, APOE ε4 may intensify the vascular health risk for MCI. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Longitudinal Effects on Early Adolescent Language: A Twin Study

PubMed Central

DeThorne, Laura Segebart; Smith, Jamie Mahurin; Betancourt, Mariana Aparicio; Petrill, Stephen A.

2016-01-01

Purpose We evaluated genetic and environmental contributions to individual differences in language skills during early adolescence, measured by both language sampling and standardized tests, and examined the extent to which these genetic and environmental effects are stable across time. Method We used structural equation modeling on latent factors to estimate additive genetic, shared environmental, and nonshared environmental effects on variance in standardized language skills (i.e., Formal Language) and productive language-sample measures (i.e., Productive Language) in a sample of 527 twins across 3 time points (mean ages 10–12 years). Results Individual differences in the Formal Language factor were influenced primarily by genetic factors at each age, whereas individual differences in the Productive Language factor were primarily due to nonshared environmental influences. For the Formal Language factor, the stability of genetic effects was high across all 3 time points. For the Productive Language factor, nonshared environmental effects showed low but statistically significant stability across adjacent time points. Conclusions The etiology of language outcomes may differ substantially depending on assessment context. In addition, the potential mechanisms for nonshared environmental influences on language development warrant further investigation. PMID:27732720

The Potential of Genetic Engineering in Agriculture to Affect Global Stability

DTIC Science & Technology

2013-04-17

manipulation in agriculture is thousands of years old, dating back to man’s first efforts of plant domestication. Over the last 200 years, and especially the...engineering.” In agriculture, genetic engineering describes the science of manipulating the genetic material (DNA) of plants by adding or taking...nature run its course. This paper does not delve into the science or even the raging safety debate over the use of genetic engineering in plants that

Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior.

PubMed

Meier, Madeline H; Slutske, Wendy S; Heath, Andrew C; Martin, Nicholas G

2011-05-01

Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior were examined in a large community sample of 6,383 adult male, female, and opposite-sex twins. Retrospective reports of childhood conduct disorder (prior to 18 years of age) were obtained when participants were approximately 30 years old, and lifetime reports of adult antisocial behavior (antisocial behavior after 17 years of age) were obtained 8 years later. Results revealed that either the genetic or the shared environmental factors influencing childhood conduct disorder differed for males and females (i.e., a qualitative sex difference), but by adulthood, these sex-specific influences on antisocial behavior were no longer apparent. Further, genetic and environmental influences accounted for proportionally the same amount of variance in antisocial behavior for males and females in childhood and adulthood (i.e., there were no quantitative sex differences). Additionally, the stability of antisocial behavior from childhood to adulthood was slightly greater for males than females. Though familial factors accounted for more of the stability of antisocial behavior for males than females, genetic factors accounted for the majority of the covariation between childhood conduct disorder and adult antisocial behavior for both sexes. The genetic influences on adult antisocial behavior overlapped completely with the genetic influences on childhood conduct disorder for both males and females. Implications for future twin and molecular genetic studies are discussed.

Sex Differences in the Genetic and Environmental Influences on Childhood Conduct Disorder and Adult Antisocial Behavior

PubMed Central

Meier, Madeline H.; Slutske, Wendy S.; Heath, Andrew C.; Martin, Nicholas G.

2011-01-01

Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior were examined in a large community sample of 6,383 adult male, female, and opposite-sex twins. Retrospective reports of childhood conduct disorder (prior to age 18) were obtained when participants were approximately 30 years old, and lifetime reports of adult antisocial behavior (antisocial behavior after age 17) were obtained eight years later. Results revealed that either the genetic or shared environmental factors influencing childhood conduct disorder differed for males and females (i.e., a qualitative sex difference), but by adulthood, these sex-specific influences on antisocial behavior were no longer apparent. Further, genetic and environmental influences accounted for proportionally the same amount of variance in antisocial behavior for males and females in childhood and adulthood (i.e., no quantitative sex differences). Additionally, the stability of antisocial behavior from childhood to adulthood was slightly greater for males than females. Though familial factors accounted for more of the stability of antisocial behavior for males than females, genetic factors accounted for the majority of the covariation between childhood conduct disorder and adult antisocial behavior for both sexes. The genetic influences on adult antisocial behavior overlapped completely with the genetic influences on childhood conduct disorder for both males and females. Implications for future twin and molecular genetic studies are discussed. PMID:21319923

Stability and change in religiousness during emerging adulthood.

PubMed

Koenig, Laura B; McGue, Matt; Iacono, William G

2008-03-01

Understanding the development of religiousness is an important endeavor because religiousness has been shown to be related to positive outcomes. The current study examined mean-level, rank-order, and individual-level change in females' religiousness during emerging adulthood. Genetic and environmental influences on religiousness and its change and stability were also investigated. Analyses were completed with an epidemiological study of 2 cohorts of twins: 1 assessed at ages 14 and 18 and a 2nd at 20 and 25. Mean levels of religiousness decreased significantly with age, while rank-order stability was high. Individual-level change was also evident. Analyses also supported the hypotheses that more change would occur in the younger cohort compared with the older cohort and that more change would occur in religious service attendance than the general index of religiousness. Twin analyses suggested that the heritability of religiousness increased with age, while the shared environmental influences decreased. For the younger cohort, change was genetic in origin, while stability was environmental. In the older cohort, change was influenced by nonshared environment and stability by both genes and family environment.

Genetic mapping of centromeres in the nine Citrus clementina chromosomes using half-tetrad analysis and recombination patterns in unreduced and haploid gametes.

PubMed

Aleza, Pablo; Cuenca, José; Hernández, María; Juárez, José; Navarro, Luis; Ollitrault, Patrick

2015-03-08

Mapping centromere locations in plant species provides essential information for the analysis of genetic structures and population dynamics. The centromere's position affects the distribution of crossovers along a chromosome and the parental heterozygosity restitution by 2n gametes is a direct function of the genetic distance to the centromere. Sexual polyploidisation is relatively frequent in Citrus species and is widely used to develop new seedless triploid cultivars. The study's objectives were to (i) map the positions of the centromeres of the nine Citrus clementina chromosomes; (ii) analyse the crossover interference in unreduced gametes; and (iii) establish the pattern of genetic recombination in haploid clementine gametes along each chromosome and its relationship with the centromere location and distribution of genic sequences. Triploid progenies were derived from unreduced megagametophytes produced by second-division restitution. Centromere positions were mapped genetically for all linkage groups using half-tetrad analysis. Inference of the physical locations of centromeres revealed one acrocentric, four metacentric and four submetacentric chromosomes. Crossover interference was observed in unreduced gametes, with variation seen between chromosome arms. For haploid gametes, a strong decrease in the recombination rate occurred in centromeric and pericentromeric regions, which contained a low density of genic sequences. In chromosomes VIII and IX, these low recombination rates extended beyond the pericentromeric regions. The genomic region corresponding to a genetic distance < 5cM from a centromere represented 47% of the genome and 23% of the genic sequences. The centromere positions of the nine citrus chromosomes were genetically mapped. Their physical locations, inferred from the genetic ones, were consistent with the sequence constitution and recombination pattern along each chromosome. However, regions with low recombination rates extended beyond the pericentromeric regions of some chromosomes into areas richer in genic sequences. The persistence of strong linkage disequilibrium between large numbers of genes promotes the stability of epistatic interactions and multilocus-controlled traits over successive generations but also maintains multi-trait associations. Identification of the centromere positions will allow the development of simple methods to analyse unreduced gamete formation mechanisms in a large range of genotypes and further modelling of genetic inheritance in sexual polyploidisation breeding schemes.

Genetic analyses of Per.C6 cell clones producing a therapeutic monoclonal antibody regarding productivity and long-term stability.

PubMed

Tsuruta, Lilian Rumi; Lopes Dos Santos, Mariana; Yeda, Fernanda Perez; Okamoto, Oswaldo Keith; Moro, Ana Maria

2016-12-01

Genetic characterization of protein-producing clones represents additional value to cell line development. In the present study, ten Per.C6 clones producing a Rebmab100 monoclonal antibody were selected using two cloning methods: six clones originated from limiting dilution cloning and four by the automated colony picker ClonePix FL. A stability program was performed for 50 generations, including 4 batches distributed along the timeframe to determine specific productivity (Qp) maintenance. Four stable clones (two from limiting dilution and two from ClonePix FL) were further evaluated. The relative mRNA expression levels of both heavy chain (HC) and light chain (LC) genes were verified at generations 0, 30-35, and 50-55 of the stability program. At generations 0 and 30-35, LC gene expression level was higher than HC gene, whereas at generation 50-55, the opposite prevailed. A high correlation was observed between Qp and HC or LC mRNA expression level for all clones at each generation analyzed along the continuous culture. The mRNA stability study was performed at steady-state culture. The LC gene displayed a higher half-life and lower decay constant than HC gene, accounting for the higher observed expression level of LC mRNA in comparison to HC mRNA. Clone R6 was highlighted due its high Qp, mRNA expression levels, and mRNA stability. Besides the benefits of applying genetic characterization for the selection of stable and high-producing clones, the present study shows for the first time the correlation between Qp and HC or LC expression levels and also mRNA stability in clones derived from human cell line Per.C6(®).

Chromosome I duplications in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKim, K.S.; Rose, A.M.

1990-01-01

We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left halfmore » of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.« less

Effects of genetics and environment on fatty acid stability in soybean seed

USDA-ARS?s Scientific Manuscript database

Although seed oil production and composition are genetically controlled, changes of oil level and oil composition across genotypes and environments such as drought and temperature were observed. The mechanisms of how genotypes interact with environment, affecting oil production and composition, are ...

ECUT: Energy Conversion and Utilization Technologies program - Biocatalysis research activity

NASA Technical Reports Server (NTRS)

Wilcox, R.

1984-01-01

The activities of the Biocatalysis Research Activity are organized into the Biocatalysis and Molecular Modeling work elements and a supporting planning and analysis function. In the Biocatalysis work element, progress is made in developing a method for stabilizing genetically engineered traits in microorganisms, refining a technique for monitoring cells that are genetically engineered, and identifying strains of fungi for highly efficient preprocessing of biomass for optimizing the efficiency of bioreactors. In the Molecular Modeling work element, a preliminary model of the behavior of enzymes is developed. A preliminary investigation of the potential for synthesizing enzymes for use in electrochemical processes is completed. Contact with industry and universities is made to define key biocatalysis technical issues and to broaden the range of potential participants in the activity. Analyses are conducted to identify and evaluate potential concepts for future research funding.

Genome-Based Genetic Tool Development for Bacillus methanolicus: Theta- and Rolling Circle-Replicating Plasmids for Inducible Gene Expression and Application to Methanol-Based Cadaverine Production.

PubMed

Irla, Marta; Heggeset, Tonje M B; Nærdal, Ingemar; Paul, Lidia; Haugen, Tone; Le, Simone B; Brautaset, Trygve; Wendisch, Volker F

2016-01-01

Bacillus methanolicus is a thermophilic methylotroph able to overproduce amino acids from methanol, a substrate not used for human or animal nutrition. Based on our previous RNA-seq analysis a mannitol inducible promoter and a putative mannitol activator gene mtlR were identified. The mannitol inducible promoter was applied for controlled gene expression using fluorescent reporter proteins and a flow cytometry analysis, and improved by changing the -35 promoter region and by co-expression of the mtlR regulator gene. For independent complementary gene expression control, the heterologous xylose-inducible system from B. megaterium was employed and a two-plasmid gene expression system was developed. Four different replicons for expression vectors were compared with respect to their copy number and stability. As an application example, methanol-based production of cadaverine was shown to be improved from 11.3 to 17.5 g/L when a heterologous lysine decarboxylase gene cadA was expressed from a theta-replicating rather than a rolling-circle replicating vector. The current work on inducible promoter systems and compatible theta- or rolling circle-replicating vectors is an important extension of the poorly developed B. methanolicus genetic toolbox, valuable for genetic engineering and further exploration of this bacterium.

Genome-Based Genetic Tool Development for Bacillus methanolicus: Theta- and Rolling Circle-Replicating Plasmids for Inducible Gene Expression and Application to Methanol-Based Cadaverine Production

PubMed Central

Irla, Marta; Heggeset, Tonje M. B.; Nærdal, Ingemar; Paul, Lidia; Haugen, Tone; Le, Simone B.; Brautaset, Trygve; Wendisch, Volker F.

2016-01-01

Bacillus methanolicus is a thermophilic methylotroph able to overproduce amino acids from methanol, a substrate not used for human or animal nutrition. Based on our previous RNA-seq analysis a mannitol inducible promoter and a putative mannitol activator gene mtlR were identified. The mannitol inducible promoter was applied for controlled gene expression using fluorescent reporter proteins and a flow cytometry analysis, and improved by changing the -35 promoter region and by co-expression of the mtlR regulator gene. For independent complementary gene expression control, the heterologous xylose-inducible system from B. megaterium was employed and a two-plasmid gene expression system was developed. Four different replicons for expression vectors were compared with respect to their copy number and stability. As an application example, methanol-based production of cadaverine was shown to be improved from 11.3 to 17.5 g/L when a heterologous lysine decarboxylase gene cadA was expressed from a theta-replicating rather than a rolling-circle replicating vector. The current work on inducible promoter systems and compatible theta- or rolling circle-replicating vectors is an important extension of the poorly developed B. methanolicus genetic toolbox, valuable for genetic engineering and further exploration of this bacterium. PMID:27713731

Systematic Analysis of the Genetic Variability That Impacts SUMO Conjugation and Their Involvement in Human Diseases

NASA Astrophysics Data System (ADS)

Xu, Hao-Dong; Shi, Shao-Ping; Chen, Xiang; Qiu, Jian-Ding

2015-07-01

Protein function has been observed to rely on select essential sites instead of requiring all sites to be indispensable. Small ubiquitin-related modifier (SUMO) conjugation or sumoylation, which is a highly dynamic reversible process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified, has shown to be especially valuable in cellular biology. Motivated by the significance of SUMO conjugation in biological processes, we report here on the first exploratory assessment whether sumoylation related genetic variability impacts protein functions as well as the occurrence of diseases related to SUMO. Here, we defined the SUMOAMVR as sumoylation related amino acid variations that affect sumoylation sites or enzymes involved in the process of connectivity, and categorized four types of potential SUMOAMVRs. We detected that 17.13% of amino acid variations are potential SUMOAMVRs and 4.83% of disease mutations could lead to SUMOAMVR with our system. More interestingly, the statistical analysis demonstrates that the amino acid variations that directly create new potential lysine sumoylation sites are more likely to cause diseases. It can be anticipated that our method can provide more instructive guidance to identify the mechanisms of genetic diseases.

Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood.

PubMed

Wesseldijk, Laura W; Bartels, Meike; Vink, Jacqueline M; van Beijsterveldt, Catharina E M; Ligthart, Lannie; Boomsma, Dorret I; Middeldorp, Christel M

2017-06-21

Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.

Regenerative potential, metabolic profile, and genetic stability of Brachypodium distachyon embryogenic calli as affected by successive subcultures.

PubMed

Mamedes-Rodrigues, T C; Batista, D S; Vieira, N M; Matos, E M; Fernandes, D; Nunes-Nesi, A; Cruz, C D; Viccini, L F; Nogueira, F T S; Otoni, W C

2018-03-01

Brachypodium distachyon, a model species for forage grasses and cereal crops, has been used in studies seeking improved biomass production and increased crop yield for biofuel production purposes. Somatic embryogenesis (SE) is the morphogenetic pathway that supports in vitro regeneration of such species. However, there are gaps in terms of studies on the metabolic profile and genetic stability along successive subcultures. The physiological variables and the metabolic profile of embryogenic callus (EC) and embryogenic structures (ES) from successive subcultures (30, 60, 90, 120, 150, 180, 210, 240, and 360-day-old subcultures) were analyzed. Canonical discriminant analysis separated EC into three groups: 60, 90, and 120 to 240 days. EC with 60 and 90 days showed the highest regenerative potential. EC grown for 90 days and submitted to SE induction in 2 mg L -1 of kinetin-supplemented medium was the highest ES producer. The metabolite profiles of non-embryogenic callus (NEC), EC, and ES submitted to principal component analysis (PCA) separated into two groups: 30 to 240- and 360-day-old calli. The most abundant metabolites for these groups were malonic acid, tryptophan, asparagine, and erythrose. PCA of ES also separated ages into groups and ranked 60- and 90-day-old calli as the best for use due to their high levels of various metabolites. The key metabolites that distinguished the ES groups were galactinol, oxaloacetate, tryptophan, and valine. In addition, significant secondary metabolites (e.g., caffeoylquinic, cinnamic, and ferulic acids) were important in the EC phase. Ferulic, cinnamic, and phenylacetic acids marked the decreases in the regenerative capacity of ES in B. distachyon. Decreased accumulations of the amino acids aspartic acid, asparagine, tryptophan, and glycine characterized NEC, suggesting that these metabolites are indispensable for the embryogenic competence in B. distachyon. The genetic stability of the regenerated plants was evaluated by flow cytometry, showing that ploidy instability in regenerated plants from B. distachyon calli is not correlated with callus age. Taken together, our data indicated that the loss of regenerative capacity in B. distachyon EC occurs after 120 days of subcultures, demonstrating that the use of EC can be extended to 90 days.

A longitudinal twin study of callous-unemotional traits during childhood.

PubMed

Henry, Jeffrey; Dionne, Ginette; Viding, Essi; Petitclerc, Amélie; Feng, Bei; Vitaro, Frank; Brendgen, Mara; Tremblay, Richard E; Boivin, Michel

2018-05-01

Previous research indicates that genetic factors largely account for the stability of callous-unemotional (CU) traits in adolescence. However, the genetic-environmental etiology of the development of CU traits has not been extensively investigated in childhood, despite work showing the reliable measurement and stability of CU traits from a young age. The aim of this study was to investigate the temporal pattern of genetic and environmental etiology of CU traits across primary school, from school entry (7 years) to middle (9 and 10 years) and late childhood (12 years). Data were collected in a population sample of twins composed of 662 twin pairs (Quebec Newborn Twin Study). CU traits were reported by teachers and analyzed using a biometric latent growth curve model and a Cholesky decomposition model. Latent growth curve analyses revealed that genetic factors explain most of the variance in the intercept of CU traits. Individual differences in change over time were not significant. The Cholesky model revealed that genetic factors at 7 years had enduring contributions to CU traits at 9, 10, and 12 years. New, modest genetic contributions appeared at 9 and 10 years. Nonshared environmental contributions were generally age-specific. No shared environmental contributions were detected. In sum, both modeling approaches showed that genetic factors underlie CU traits during childhood. Initial and new genetic contributions arise during this period. Environments have substantial contributions, over and above genetic factors. Future research should investigate the source of genetic risk associated with CU traits. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Identification and in silico characterization of p.G380R substitution in FGFR3, associated with achondroplasia in a non-consanguineous Pakistani family.

PubMed

Ajmal, Muhammad; Mir, Asif; Shoaib, Muhammad; Malik, Salman Akbar; Nasir, Muhammad

2017-07-05

The dimerization efficiency of FGFR3 transmembrane domain plays a critical role in the formation of a normal skeleton through the negative regulation of bone development. Recently, gain-of-function mutations in the transmembrane domain of FGFR3 has been described associated with an aberrant negative regulation, leading to the development of achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). Here, we describe a non-consanguineous Pakistani family with achondroplasia to explain hereditary basis of the disease. PCR-based linkage analysis using microsatellite markers was employed to localize the disease gene. Gene specific intronic primers were used to amplify the genomic DNA from all affected as well as phenotypically healthy individuals. Amplified PCR products were then subjected to Sanger sequencing and RFLP analysis to identify a potentially pathogenic mutation. The impact of identified mutation on FGFR3 protein's structure and stability was highlighted through different bioinformatics tools. Genetic screening of the family revealed a previously reported heterozygous c.1138 G > A (p.G380R) mutation in the coding exon 8 of FGFR3 gene. Identified genetic variation was confirmed in all affected individuals while healthy individuals and controls were found genotypically normal. The results were further validated by RFLP analysis as c.1138 G > A substitution generates a unique recognition site for SfcI endonuclease. Following SfcI digestion, the electrophoretic pattern of three bands/DNA fragments for each patient is indicative of heterozygous status of the disease allele. In silico studies of the mutant FGFR3 protein predicted to adversely affect the stability of FGFR3 protein. Mutation in the transmembrane domain may adversely affect the dimerization efficiency and overall stability of the FGFR3, leading to a constitutively active protein. As a result, an uncontrolled intracellular signaling or negative bone growth regulation leads to achondroplasia. Our findings support the fact that p.G380R is a common mutation among diverse population of the world and like other countries, can be used as a molecular diagnosis marker for achondroplasia in Pakistan.

Childhood and adolescent anxiety and depression: beyond heritability.

PubMed

Franić, Sanja; Middeldorp, Christel M; Dolan, Conor V; Ligthart, Lannie; Boomsma, Dorret I

2010-08-01

To review the methodology of behavior genetics studies addressing research questions that go beyond simple heritability estimation and illustrate these using representative research on childhood and adolescent anxiety and depression. The classic twin design and its extensions may be used to examine age and gender differences in the genetic determinants of complex traits and disorders, the role of genetic factors in explaining comorbidity, the interaction of genes and the environment, and the effect of social interaction among family members. An overview of the methods typically employed to address such questions is illustrated by a review of 34 recent studies on childhood anxiety and depression. The review provides relatively consistent evidence for small to negligible sex differences in the genetic etiology of childhood anxiety and depression, a substantial role of genetic factors in accounting for the temporal stability of these disorders, a partly genetic basis of the comorbidity between anxiety and depression, a possible role of the interaction between genotype and the environment in affecting liability to these disorders, a role of genotype-environment correlation, and a minor, if any, etiological role of sibling interaction. The results clearly demonstrate a role for genetic factors in the etiology and temporal stability of individual differences in childhood anxiety and depression. Clinical implications of the findings are discussed. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Exploring the Metabolic Stability of Engineered Hairy Roots after 16 Years Maintenance.

PubMed

Häkkinen, Suvi T; Moyano, Elisabeth; Cusidó, Rosa M; Oksman-Caldentey, Kirsi-Marja

2016-01-01

Plants remain a major source of new drugs, leads and fine chemicals. Cell cultures deriving from plants offer a fascinating tool to study plant metabolic pathways and offer large scale production systems for valuable compounds - commercial examples include compounds such as paclitaxel. The major constraint with undifferentiated cell cultures is that they are generally considered to be genetically unstable and cultured cells tend to produce low yields of secondary metabolites especially over time. Hairy roots, a tumor tissue caused by infection of Agrobacterium rhizogenes is a relevant alternative for plant secondary metabolite production for being fast growing, able to grow without phytohormones, and displaying higher stability than undifferentiated cells. Although genetic and metabolic stability has often been connected to transgenic hairy roots, there are only few reports on how a very long-term subculturing effects on the production capacity of hairy roots. In this study, hairy roots producing high tropane alkaloid levels were subjected to 16-year follow-up in relation to genetic and metabolic stability. Cryopreservation method for hairy roots of Hyoscyamus muticus was developed to replace laborious subculturing, and although the post-thaw recovery rates remained low, the expression of transgene remained unaltered in cryopreserved roots. It was shown that although displaying some fluctuation in the metabolite yields, even an exceedingly long-term subculturing was successfully applied without significant loss of metabolic activity.

Seedling development and evaluation of genetic stability of cryopreserved Dendrobium hybrid mature seeds.

PubMed

Galdiano, Renato Fernandes; de Macedo Lemos, Eliana Gertrudes; de Faria, Ricardo Tadeu; Vendrame, Wagner Aparecido

2014-03-01

Vitrification, a simple, fast, and recommended cryopreservation method for orchid germplasm conservation, was evaluated for Dendrobium hybrid "Dong Yai" mature seeds. The genetic stability of regenerated seedlings was also evaluated using flow cytometry. Mature seeds from this hybrid were submitted to plant vitrification solution (PVS2) for 0, 0.5, 1, 2, 3, 4, 5, or 6 h at 0 °C. Subsequently, they were plunged into liquid nitrogen (LN) at -196 °C for 1 h and recovered in half-strength Murashige and Skoog culture medium (1/2 MS), and seed germination was evaluated after 30 days. Seeds directly submitted to LN did not germinate after cryopreservation. Seeds treated with PVS2 between 1 and 3 h presented the best germination (between 51 and 58%), although longer exposure to PVS2 returned moderated germination (39%). Germinated seeds were further subcultured in P-723 culture medium and developed whole seedlings in vitro after 180 days, with no abnormal characteristics, diseases, or nutritional deficiencies. Seedlings were successfully acclimatized under greenhouse conditions with over 80% survival. Flow cytometry analysis revealed no chromosomal changes on vitrified seedlings, as well as seedlings germinated from the control treatment (direct exposure to LN). These findings indicate that vitrification is a feasible and safe germplasm cryopreservation method for commercial Dendrobium orchid hybrid conservation.

Does cross-generational epigenetic inheritance contribute to cultural continuity?

PubMed Central

Pembrey, Marcus E

2018-01-01

Abstract Human studies of cross-generational epigenetic inheritance have to consider confounding by social patterning down the generations, often referred to as ‘cultural inheritance’. This raises the question to what extent is ‘cultural inheritance’ itself epigenetically mediated rather than just learnt. Human studies of non-genetic inheritance have demonstrated that, beyond foetal life, experiences occurring in mid-childhood before puberty are the most likely to be associated with cross-generational responses in the next generation(s). It is proposed that cultural continuity is played out along the axis, or ‘payoff’, between responsiveness and stability. During the formative years of childhood a stable family and/or home permits small children to explore and thereby learn. To counter disruptions to this family home ideal, cultural institutions such as local schools, religious centres and market places emerged to provide ongoing stability, holding the received wisdom of the past in an accessible state. This cultural support allows the growing child to freely indulge their responsiveness. Some of these prepubertal experiences induce epigenetic responses that also transfer molecular signals to the gametes through which they contribute to the conception of future offspring. In parallel co-evolution with growing cultural support for increasing responsiveness, ‘runaway’ responsiveness is countered by the positive selection of genetic variants that dampen responsiveness. Testing these ideas within longitudinal multigenerational cohorts will need information on ancestors/parents’ own communities and experiences (Exposome scans) linked to ongoing Phenome scans on grandchildren; coupled with epigenome analysis, metastable epialleles and DNA methylation age. Interactions with genetic variants affecting responsiveness should help inform the broad hypothesis. PMID:29732169

Does cross-generational epigenetic inheritance contribute to cultural continuity?

PubMed

Pembrey, Marcus E

2018-04-01

Human studies of cross-generational epigenetic inheritance have to consider confounding by social patterning down the generations, often referred to as 'cultural inheritance'. This raises the question to what extent is 'cultural inheritance' itself epigenetically mediated rather than just learnt. Human studies of non-genetic inheritance have demonstrated that, beyond foetal life, experiences occurring in mid-childhood before puberty are the most likely to be associated with cross-generational responses in the next generation(s). It is proposed that cultural continuity is played out along the axis, or 'payoff', between responsiveness and stability. During the formative years of childhood a stable family and/or home permits small children to explore and thereby learn. To counter disruptions to this family home ideal, cultural institutions such as local schools, religious centres and market places emerged to provide ongoing stability, holding the received wisdom of the past in an accessible state. This cultural support allows the growing child to freely indulge their responsiveness. Some of these prepubertal experiences induce epigenetic responses that also transfer molecular signals to the gametes through which they contribute to the conception of future offspring. In parallel co-evolution with growing cultural support for increasing responsiveness, 'runaway' responsiveness is countered by the positive selection of genetic variants that dampen responsiveness. Testing these ideas within longitudinal multigenerational cohorts will need information on ancestors/parents' own communities and experiences (Exposome scans) linked to ongoing Phenome scans on grandchildren; coupled with epigenome analysis, metastable epialleles and DNA methylation age. Interactions with genetic variants affecting responsiveness should help inform the broad hypothesis.

The effects of intraspecific competition and stabilizing selection on a polygenic trait.

PubMed Central

Bürger, Reinhard; Gimelfarb, Alexander

2004-01-01

The equilibrium properties of an additive multilocus model of a quantitative trait under frequency- and density-dependent selection are investigated. Two opposing evolutionary forces are assumed to act: (i) stabilizing selection on the trait, which favors genotypes with an intermediate phenotype, and (ii) intraspecific competition mediated by that trait, which favors genotypes whose effect on the trait deviates most from that of the prevailing genotypes. Accordingly, fitnesses of genotypes have a frequency-independent component describing stabilizing selection and a frequency- and density-dependent component modeling competition. We study how the equilibrium structure, in particular, number, degree of polymorphism, and genetic variance of stable equilibria, is affected by the strength of frequency dependence, and what role the number of loci, the amount of recombination, and the demographic parameters play. To this end, we employ a statistical and numerical approach, complemented by analytical results, and explore how the equilibrium properties averaged over a large number of genetic systems with a given number of loci and average amount of recombination depend on the ecological and demographic parameters. We identify two parameter regions with a transitory region in between, in which the equilibrium properties of genetic systems are distinctively different. These regions depend on the strength of frequency dependence relative to pure stabilizing selection and on the demographic parameters, but not on the number of loci or the amount of recombination. We further study the shape of the fitness function observed at equilibrium and the extent to which the dynamics in this model are adaptive, and we present examples of equilibrium distributions of genotypic values under strong frequency dependence. Consequences for the maintenance of genetic variation, the detection of disruptive selection, and models of sympatric speciation are discussed. PMID:15280253

Two novel CHN1 mutations in two families with Duane’s retraction syndrome

PubMed Central

Chan, Wai-Man; Miyake, Noriko; Zhu-Tam, Lily; Andrews, Caroline; Engle, Elizabeth C.

2012-01-01

Objective To determine the genetic cause of Duane’s retraction syndrome (DRS) in two families segregating DRS as an autosomal dominant trait. Method Members of two unrelated pedigrees were enrolled in an ongoing genetic study. Linkage analysis was performed using fluorescent microsatellite markers flanking the CHN1 locus. Probands and family members were screened for CHN1 mutations. Results Of the six clinically affected individuals in the two pedigrees, three have bilateral and three have unilateral DRS. Both pedigrees are consistent with linkage to the DURS2 locus, one with complete and one with incomplete penetrance. Sequence analysis revealed the pedigrees segregate novel heterozygous missense CHN1 mutations, c.422C>T and c.754C>T, predicted to result in α2-chimaerin amino acid substitutions P141L and P252S, respectively. Conclusion Genetic analysis of two pedigrees segregating nonsyndromic DRS reveals two novel mutations in CHN1, bringing the number of DRS pedigrees know to harbor CHN1 mutations, and the number of unique CHN1 mutations, from seven to nine. Both mutations identified in this study alter residues that participate in intramolecular interactions that stabilize the inactive, closed conformation of α2-chimerin, and thus are predicted to result in its hyper-activation. Moreover, amino acid residue P252 was altered to a different residue in a previously reported DRS pedigree; thus, this is the first report of two CHN1 mutations altering the same residue, further supporting a gain-of-function etiology. Clinical Relevance Members of families segregating DRS as an autosomal dominant trait should be screened for mutations in the CHN1 gene, enhancing genetic counseling and permitting earlier diagnosis. PMID:21555619

Post-ExSELEX stabilization of an unnatural-base DNA aptamer targeting VEGF165 toward pharmaceutical applications.

PubMed

Kimoto, Michiko; Nakamura, Mana; Hirao, Ichiro

2016-09-06

A new technology, genetic alphabet expansion using artificial bases (unnatural bases), has created high-affinity DNA ligands (aptamers) that specifically bind to target proteins by ExSELEX (genetic alphabet Expansion for Systematic Evolution of Ligands by EXponential enrichment). We recently found that the unnatural-base DNA aptamers can be stabilized against nucleases, by introducing an extraordinarily stable, unique hairpin DNA (mini-hairpin DNA) and by reinforcing the stem region with G-C pairs. Here, to establish this aptamer generation method, we examined the stabilization of a high-affinity anti-VEGF165 unnatural-base DNA aptamer. The stabilized aptamers displayed significantly increased thermal and nuclease stabilities, and furthermore, exhibited higher affinity to the target. As compared to the well-known anti-VEGF165 RNA aptamer, pegaptanib (Macugen), our aptamers did not require calcium ions for binding to VEGF165 Biological experiments using cultured cells revealed that our stabilized aptamers efficiently inhibited the interaction between VEGF165 and its receptor, with the same or slightly higher efficiency than that of the pegaptanib RNA aptamer. The development of cost-effective and calcium ion-independent high-affinity anti-VEGF165 DNA aptamers encourages further progress in diagnostic and therapeutic applications. In addition, the stabilization process provided additional information about the key elements required for aptamer binding to VEGF165. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing.

PubMed

Yi, Yanjun; Tian, Zhuowei; Ju, Houyu; Ren, Guoxin; Hu, Jingzhou

2017-06-01

Oral cancer is a serious disease caused by environmental factors and/or susceptible genes. In the present study, in order to identify useful genetic biomarkers for cancer prediction and prevention, and for personalized treatment, we detected somatic mutations in 5 pairs of oral cancer tissues and blood samples using whole exome sequencing (WES). Finally, we confirmed a novel nonsense single-nucleotide polymorphism (SNP; chr19:15288426A>C) in the NOTCH3 gene with sanger sequencing, which resulted in a N1438T mutation in the protein sequence. Using multiple in silico analyses, this variant was found to mildly damaging effects on the NOTCH3 gene, which was supported by the results from analyses using PANTHER, SNAP and SNPs&GO. However, further analysis using Mutation Taster revealed that this SNP had a probability of 0.9997 to be 'disease causing'. In addition, we performed 3D structure simulation analysis and the results suggested that this variant had little effect on the solubility and hydrophobicity of the protein and thus on its function; however, it decreased the stability of the protein by increasing the total energy following minimization (-1,051.39 kcal/mol for the mutant and -1,229.84 kcal/mol for the native) and decreasing one stabilizing residue of the protein. Less stability of the N1438T mutant was also supported by analysis using I-Mutant with a DDG value of -1.67. Overall, the present study identified and confirmed a novel mutation in the NOTCH3 gene, which may decrease the stability of NOTCH3, and may thus prove to be helpful in cancer prognosis.

On spectral techniques in analysis of Boolean networks

NASA Astrophysics Data System (ADS)

Kesseli, Juha; Rämö, Pauli; Yli-Harja, Olli

2005-06-01

In this work we present results that can be used for analysis of Boolean networks. The results utilize Fourier spectra of the functions in the network. An accurate formula is given for Derrida plots of networks of finite size N based on a result on Boolean functions presented in another context. Derrida plots are widely used to examine the stability issues of Boolean networks. For the limit N→∞, we give a computationally simple form that can be used as a good approximation for rather small networks as well. A formula for Derrida plots of random Boolean networks (RBNs) presented earlier in the literature is given an alternative derivation. It is shown that the information contained in the Derrida plot is equal to the average Fourier spectrum of the functions in the network. In the case of random networks the mean Derrida plot can be obtained from the mean spectrum of the functions. The method is applied to real data by using the Boolean functions found in genetic regulatory networks of eukaryotic cells in an earlier study. Conventionally, Derrida plots and stability analysis have been computed with statistical sampling resulting in poorer accuracy.

A Longitudinal Twin Study on the Association between ADHD Symptoms and Reading

ERIC Educational Resources Information Center

Greven, Corina U.; Rijsdijk, Fruhling V.; Asherson, Philip; Plomin, Robert

2012-01-01

Background: Attention deficit hyperactivity disorder (ADHD) and reading disability commonly co-occur because of shared genetic risk factors. However, the stability and change of these genetic influences and the predictive relationships underlying this association longitudinally remain unclear. Methods: ADHD symptoms and reading were assessed as…

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

PubMed

Lacourse, E; Boivin, M; Brendgen, M; Petitclerc, A; Girard, A; Vitaro, F; Paquin, S; Ouellet-Morin, I; Dionne, G; Tremblay, R E

2014-09-01

Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

Quantitative mutant analysis of viral quasispecies by chip-based matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry

PubMed Central

Amexis, Georgios; Oeth, Paul; Abel, Kenneth; Ivshina, Anna; Pelloquin, Francois; Cantor, Charles R.; Braun, Andreas; Chumakov, Konstantin

2001-01-01

RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants having one or more consensus sequences. An adequate description of the genomic structure of such viral populations must include the consensus sequence(s) plus a quantitative assessment of sequence heterogeneities. For example, in quality control of live attenuated viral vaccines, the presence of even small quantities of mutants or revertants may indicate incomplete or unstable attenuation that may influence vaccine safety. Previously, we demonstrated the monitoring of oral poliovirus vaccine with the use of mutant analysis by PCR and restriction enzyme cleavage (MAPREC). In this report, we investigate genetic variation in live attenuated mumps virus vaccine by using both MAPREC and a platform (DNA MassArray) based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Mumps vaccines prepared from the Jeryl Lynn strain typically contain at least two distinct viral substrains, JL1 and JL2, which have been characterized by full length sequencing. We report the development of assays for characterizing sequence variants in these substrains and demonstrate their use in quantitative analysis of substrains and sequence variations in mixed virus cultures and mumps vaccines. The results obtained from both the MAPREC and MALDI-TOF methods showed excellent correlation. This suggests the potential utility of MALDI-TOF for routine quality control of live viral vaccines and for assessment of genetic stability and quantitative monitoring of genetic changes in other RNA viruses of clinical interest. PMID:11593021

DNA profiling of Tilapia guinasana, a species endemic to a single sinkhole, to determine the genetic divergence between color forms.

PubMed

Nxomani, C; Ribbink, A J; Kirby, R

1999-06-01

Northwestern South Africa and Namibia contain a number of sinkholes in the dolomitic rock formations found in this area. These contain isolated populations of Tilapia. Most contain Tilapia sparmanii, but the one in Namibia, Guinas, is of particular interest as it contains the endemic species, Tilapia guinasana, which exhibits none sex-limited polychromatisms, which is unique for Tilapia. This sinkhole is under environmental threat, particularly as a result of being a recreational diving site. This study, using randomly amplified polymorphic DNA sequences (RAPDs), when analyzed using analysis of variance (ANOVA), shows that the colour forms of Tilapia guinasana are genetically distinct. This confirms previous evidence that assortative mating between color forms takes place. The various possible hypotheses for the occurrence and genetic stability of the color polymorphism are discussed. Further, a new hypothesis is put forward based on a need to maximize outbreeding in fully isolated population with no possibility of increase in size above the maximum and limited carrying capacity of the sinkhole.

[Action of two pyrazine-containing chemosignals on cells of bone marrow and testes in male house mouse Mus musculus L].

PubMed

Daev, E V; Vyborova, A M; Kazarova, V É; Dukel'skaia, A V

2012-01-01

Evolutionary conservative chemosignal 2,5-dimethylpyrazin that is pheromone in female mice has been shown to increase frequency of mitotic aberrations analyzed with aid of metaphasic and ana-telophasic analysis in bone marrow cells. Replacement of one of methyl radicals in the pheromone molecule by the carboxyl radical reveals specificity of action of the used derivative: the frequency of disturbances revealed only by the ana-telophasic analysis increases, whereas by the metaphasic analysis, no induction of disturbance is detected. In the sperm head abnormality test there is shown a rise of the anomalies by both compounds. Possible mechanisms of specific action of the tested substances on stability of genetic apparatus of the bone marrow dividing cells in the house mouse are discussed.

Genetic heterogeneity underlying variation in a locally adaptive clinal trait in Pinus sylvestris revealed by a Bayesian multipopulation analysis.

PubMed

Kujala, S T; Knürr, T; Kärkkäinen, K; Neale, D B; Sillanpää, M J; Savolainen, O

2017-05-01

Local adaptation is a common feature of plant and animal populations. Adaptive phenotypic traits are genetically differentiated along environmental gradients, but the genetic basis of such adaptation is still poorly known. Genetic association studies of local adaptation combine data over populations. Correcting for population structure in these studies can be problematic since both selection and neutral demographic events can create similar allele frequency differences between populations. Correcting for demography with traditional methods may lead to eliminating some true associations. We developed a new Bayesian approach for identifying the loci underlying an adaptive trait in a multipopulation situation in the presence of possible double confounding due to population stratification and adaptation. With this method we studied the genetic basis of timing of bud set, a surrogate trait for timing of yearly growth cessation that confers local adaptation to the populations of Scots pine (Pinus sylvestris). Population means of timing of bud set were highly correlated with latitude. Most effects at individual loci were small. Interestingly, we found genetic heterogeneity (that is, different sets of loci associated with the trait) between the northern and central European parts of the cline. We also found indications of stronger stabilizing selection toward the northern part of the range. The harsh northern conditions may impose greater selective pressure on timing of growth cessation, and the relative importance of different environmental cues used for tracking the seasons might differ depending on latitude of origin.

Epigenetic regulation of ageing: linking environmental inputs to genomic stability

PubMed Central

Benayoun, Bérénice A.; Pollina, Elizabeth A.; Brunet, Anne

2016-01-01

Preface Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodeling by environmental stimuli impacts several aspects of transcription and genomic stability, with important consequences on longevity, and outline epigenetic differences between the ‘mortal soma’ and the ‘immortal germline’. Finally, we discuss the inheritance of ageing characteristics and potential chromatin-based strategies to delay or reverse hallmarks of ageing or age-related diseases. PMID:26373265

Evidence of directional and stabilizing selection in contemporary humans.

PubMed

Sanjak, Jaleal S; Sidorenko, Julia; Robinson, Matthew R; Thornton, Kevin R; Visscher, Peter M

2018-01-02

Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.

Patterns in longitudinal growth of refraction in Southern Chinese children: cluster and principal component analysis.

PubMed

Chen, Yanxian; Chang, Billy Heung Wing; Ding, Xiaohu; He, Mingguang

2016-11-22

In the present study we attempt to use hypothesis-independent analysis in investigating the patterns in refraction growth in Chinese children, and to explore the possible risk factors affecting the different components of progression, as defined by Principal Component Analysis (PCA). A total of 637 first-born twins in Guangzhou Twin Eye Study with 6-year annual visits (baseline age 7-15 years) were available in the analysis. Cluster 1 to 3 were classified after a partitioning clustering, representing stable, slow and fast progressing groups of refraction respectively. Baseline age and refraction, paternal refraction, maternal refraction and proportion of two myopic parents showed significant differences across the three groups. Three major components of progression were extracted using PCA: "Average refraction", "Acceleration" and the combination of "Myopia stabilization" and "Late onset of refraction progress". In regression models, younger children with more severe myopia were associated with larger "Acceleration". The risk factors of "Acceleration" included change of height and weight, near work, and parental myopia, while female gender, change of height and weight were associated with "Stabilization", and increased outdoor time was related to "Late onset of refraction progress". We therefore concluded that genetic and environmental risk factors have different impacts on patterns of refraction progression.

Analysis of galactosemia-linked mutations of GALT enzyme using a computational biology approach.

PubMed

Facchiano, A; Marabotti, A

2010-02-01

We describe the prediction of the structural and functional effects of mutations on the enzyme galactose-1-phosphate uridyltransferase related to the genetic disease galactosemia, using a fully computational approach. One hundred and seven single-point mutants were simulated starting from the structural model of the enzyme obtained by homology modeling methods. Several bioinformatics programs were then applied to each resulting mutant protein to analyze the effect of the mutations. The mutations have a direct effect on the active site, or on the dimer assembly and stability, or on the monomer stability. We describe how mutations may exert their effect at a molecular level by altering H-bonds, salt bridges, secondary structure or surface features. The alteration of protein stability, at level of monomer and/or dimer, is the main effect observed. We found an agreement between our results and the functional experimental data available in literature for some mutants. The data and analyses for all the mutants are fully available in the web-accessible database hosted at http://bioinformatica.isa.cnr.it/GALT.

Evolution driven structural changes in CENP-E motor domain.

PubMed

Kumar, Ambuj; Kamaraj, Balu; Sethumadhavan, Rao; Purohit, Rituraj

2013-06-01

Genetic evolution corresponds to various biochemical changes that are vital development of new functional traits. Phylogenetic analysis has provided an important insight into the genetic closeness among species and their evolutionary relationships. Centromere-associated protein-E (CENP-E) protein is vital for maintaining cell cycle and checkpoint signal mechanisms are vital for recruitment process of other essential kinetochore proteins. In this study we have focussed on the evolution driven structural changes in CENP-E motor domain among primate lineage. Through molecular dynamics simulation and computational chemistry approaches we examined the changes in ATP binding affinity and conformational deviations in human CENP-E motor domain as compared to the other primates. Root mean square deviation (RMSD), Root mean square fluctuation (RMSF), Radius of gyration (Rg) and principle component analysis (PCA) results together suggested a gain in stability level as we move from tarsier towards human. This study provides a significant insight into how the cell cycle proteins and their corresponding biochemical activities are evolving and illustrates the potency of a theoretical approach for assessing, in a single study, the structural, functional, and dynamical aspects of protein evolution.

The human genome: a multifractal analysis

PubMed Central

2011-01-01

Background Several studies have shown that genomes can be studied via a multifractal formalism. Recently, we used a multifractal approach to study the genetic information content of the Caenorhabditis elegans genome. Here we investigate the possibility that the human genome shows a similar behavior to that observed in the nematode. Results We report here multifractality in the human genome sequence. This behavior correlates strongly on the presence of Alu elements and to a lesser extent on CpG islands and (G+C) content. In contrast, no or low relationship was found for LINE, MIR, MER, LTRs elements and DNA regions poor in genetic information. Gene function, cluster of orthologous genes, metabolic pathways, and exons tended to increase their frequencies with ranges of multifractality and large gene families were located in genomic regions with varied multifractality. Additionally, a multifractal map and classification for human chromosomes are proposed. Conclusions Based on these findings, we propose a descriptive non-linear model for the structure of the human genome, with some biological implications. This model reveals 1) a multifractal regionalization where many regions coexist that are far from equilibrium and 2) this non-linear organization has significant molecular and medical genetic implications for understanding the role of Alu elements in genome stability and structure of the human genome. Given the role of Alu sequences in gene regulation, genetic diseases, human genetic diversity, adaptation and phylogenetic analyses, these quantifications are especially useful. PMID:21999602

Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers.

PubMed

Silva, A V C; Nascimento, A L S; Vitória, M F; Rabbani, A R C; Soares, A N R; Lédo, A S

2017-02-23

Banana (Musa spp) is a fruit species frequently cultivated and consumed worldwide. Molecular markers are important for estimating genetic diversity in germplasm and between genotypes in breeding programs. The objective of this study was to analyze the genetic diversity of 21 banana genotypes (FHIA 23, PA42-44, Maçã, Pacovan Ken, Bucaneiro, YB42-47, Grand Naine, Tropical, FHIA 18, PA94-01, YB42-17, Enxerto, Japira, Pacovã, Prata-Anã, Maravilha, PV79-34, Caipira, Princesa, Garantida, and Thap Maeo), by using inter-simple sequence repeat (ISSR) markers. Material was generated from the banana breeding program of Embrapa Cassava & Fruits and evaluated at Embrapa Coastal Tablelands. The 12 primers used in this study generated 97.5% polymorphism. Four clusters were identified among the different genotypes studied, and the sum of the first two principal components was 48.91%. From the Unweighted Pair Group Method using Arithmetic averages (UPGMA) dendrogram, it was possible to identify two main clusters and subclusters. Two genotypes (Garantida and Thap Maeo) remained isolated from the others, both in the UPGMA clustering and in the principal cordinate analysis (PCoA). Using ISSR markers, we could analyze the genetic diversity of the studied material and state that these markers were efficient at detecting sufficient polymorphism to estimate the genetic variability in banana genotypes.

Pedigree analysis in the Austrian Noriker draught horse: genetic diversity and the impact of breeding for coat colour on population structure.

PubMed

Druml, T; Baumung, R; Sölkner, J

2009-10-01

The pedigree of the current Austrian Noriker draught horse population comprising 2808 horses was traced back to the animals considered as founders of this breed. In total, the number of founders was 1991, the maximum pedigree length was 31 generations, with an average of 12.3 complete generations. Population structure in this autochthonous Austrian draught horse breed is defined by seven breeding regions (Carinthia, Lower Austria, Salzburg, Styria, Tyrol, Upper Austria and Vorarlberg) or through six coat colour groups (Bay, Black, Chestnut, Roan, Leopard, Tobiano). Average inbreeding coefficients within the breeding regions ranged from 4.5% to 5.5%; for the colour groups, the coefficients varied from 3.5% to 5.9%. Other measures of genetic variability like the effective number of founders, ancestors and founder genomes revealed a slightly different genetic background of the subpopulations. Average co-ancestries between and within breeding areas showed that the Salzburg population may be considered as the nucleus or original stock whereas all other subpopulations showed high relationship to horses from Salzburg. The target of draught horse breeding in the 21st century does not meet the breeding concept of maximizing genetic gains any more. Stabilizing selection takes place. In this study, we show that demographic factors as well as structure given by different coat colours helped to maintain genetic diversity in this endangered horse breed.

Comparative study of endophytic and endophytic diazotrophic bacterial communities across rice landraces grown in the highlands of northern Thailand.

PubMed

Rangjaroen, Chakrapong; Rerkasem, Benjavan; Teaumroong, Neung; Sungthong, Rungroch; Lumyong, Saisamorn

2014-01-01

Communities of bacterial endophytes within the rice landraces cultivated in the highlands of northern Thailand were studied using fingerprinting data of 16S rRNA and nifH genes profiling by polymerase chain reaction-denaturing gradient gel electrophoresis. The bacterial communities' richness, diversity index, evenness, and stability were varied depending on the plant tissues, stages of growth, and rice cultivars. These indices for the endophytic diazotrophic bacteria within the landrace rice Bue Wah Bo were significantly the lowest. The endophytic bacteria revealed greater diversity by cluster analysis with seven clusters compared to the endophytic diazotrophic bacteria (three clusters). Principal component analysis suggested that the endophytic bacteria showed that the community structures across the rice landraces had a higher stability than those of the endophytic diazotrophic bacteria. Uncultured bacteria were found dominantly in both bacterial communities, while higher generic varieties were observed in the endophytic diazotrophic bacterial community. These differences in bacterial communities might be influenced either by genetic variation in the rice landraces or the rice cultivation system, where the nitrogen input affects the endophytic diazotrophic bacterial community.

Generation of β-glucuronidase reporter-tagged strain to monitor Ustilaginoidea virens infection in rice.

PubMed

Andargie, Mebeaselassie; Yang, Chao; Li, Jianxiong

2016-12-01

An Agrobacterium-mediated genetic transformation system for the rice false smut fungus Ustilaginoidea virens was developed using conidia as recipients. A binary vector, pCAMBIA1301-P gpdA -GUS-T trpC , was constructed. The gpdA promoter (P gpdA ) from Aspergillus nidulans was used to drive the expression of the β-glucuronidase (GUS) gene which enabled GUS activity visualization. The conidia transformation efficiency reached approximately 110 to 250 transformants per 1×10 5 conidia. Based on the analysis made on five successive generations of subcultures and PCR, the pCAMBIA1301-GUS cassette had integrated into the genomes of all transformants and clearly showed mitotic stability. The novel reporter vector constructed will promote the functional characterization of genes and the construction of genetically engineered strains of this important fungus. Copyright © 2016 Elsevier B.V. All rights reserved.

Epigenetic changes detected in micropropagated hop plants.

PubMed

Peredo, Elena L; Arroyo-García, Rosa; Revilla, M Angeles

2009-07-01

Micropropagation is a widely used technique in hops (Humulus lupulus L.). However, to the best of our knowledge, the genetic and epigenetic stability of the microplants has never been tested before. In the present study, two hop accessions were established in vitro and micropropagated for 2 years. The genetic and epigenetic stability of the in vitro plants was analyzed with several molecular techniques: random amplified DNA polymorphism (RAPD), retrotransposon microsatellite amplified polymorphism (REMAP), and methylation-sensitive amplification polymorphism (MSAP). No genetic variation among control and treated plants was found, even after 12 cycles of micropropagation. Epigenetic variation was detected, first, when field and in vitro samples were compared. Nearly a 30% of the detected fragments presented the same pattern of alterations in all the vitroplants. Second, lower levels of epigenetic variation were detected among plants from the different subcultures. Part of this detected variation seemed to be accumulated along the 12 sequential subcultures tested.

The genomic landscape of human cellular circadian variation points to a novel role for the signalosome

PubMed Central

Gaspar, Ludmila; Howald, Cedric; Popadin, Konstantin; Maier, Bert; Mauvoisin, Daniel; Moriggi, Ermanno; Gutierrez-Arcelus, Maria; Falconnet, Emilie; Borel, Christelle; Kunz, Dieter; Kramer, Achim; Gachon, Frederic; Dermitzakis, Emmanouil T; Antonarakis, Stylianos E

2017-01-01

The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome. We further show that the signalosome complex is imported into the nucleus in timed fashion to stabilize the essential circadian protein BMAL1, a novel mechanism to oppose its proteasome-mediated degradation. Thus, circadian clock properties depend in part upon a genetically-encoded competition between stabilizing and destabilizing forces, and genetic alterations in these mechanisms provide one explanation for human chronotype. PMID:28869038

Clinicopathological and molecular stability and methylation analyses of gastric papillary adenocarcinoma.

PubMed

Uesugi, Noriyuki; Sugai, Tamotsu; Sugimoto, Ryo; Eizuka, Makoto; Fujita, Yasuko; Sato, Ayaka; Osakabe, Mitsumasa; Ishida, Kazuyuki; Koeda, Keisuke; Sasaki, Akira; Matsumoto, Takayuki

2017-10-01

The molecular alterations and pathological features of gastric papillary adenocarcinoma (GPA) remain unknown. We examined GPA samples and compared their molecular and pathological characteristics with those of gastric tubular adenocarcinoma (GTA). Additionally, we identified pathological and molecular features of GPA that vary with microsatellite stability. In the present study, samples from 63 GPA patients and 47 GTA patients were examined using a combination of polymerase chain reaction (PCR)-microsatellite assays and PCR-pyrosequencing in order to detect microsatellite instability (microsatellite instability, MSI; microsatellite stable, MSS), methylation status (low methylation, intermediate methylation and high methylation level), and chromosomal AI in multiple cancer-related loci. Additionally, the expression levels of TP53 and Her2 were evaluated using immunohistochemistry. GTA and GPA are statistically different in their frequency of pathological features, including mucinous, poorly differentiated and invasive micropapillary components. Clear genetic patterns differentiating GPA and GTA could not be identified with a hierarchical cluster analysis, but microsatellite stability was linked with TP53 and Her2 overexpression. Methylation status in GPA was also associated with the development of high microsatellite instability. However, no pathological differences were associated with microsatellite stability. We suggest that although molecular alterations in a subset of GPAs are closely associated with microsatellite stability, they play a minor role in GPA carcinogenesis. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Observed Personality in Childhood: Psychometric and Behavioral Genetic Evidence of Two Broad Personality Factors

PubMed Central

Wang, Zhe; Chen, Nan; Petrill, Stephen A.; Deater-Deckard, Kirby

2014-01-01

We examined broad dimensions of children’s personalities (total n = 1056; age = 3.5 to 12 years) based on observers’ perceptions following a few hours of structured interaction. Siblings’ behaviors during a two-hour cognitive assessment in the home were rated separately by two different observers. Exploratory and confirmatory factor analyses clearly revealed a two-factor solution in three different samples. There was correspondence between parent-rated temperament and the observer-rated factors. Cross-sectional analyses indicated lower Plasticity among older children and higher Stability among older children. Sex differences were negligible. Plasticity and Stability were correlated in the .2 to .3 range. Most of the sibling similarity in the Plasticity was due to additive genetic influences, whereas most sibling similarity in Stability was attributable to shared environmental influences. The findings implicate a biometric factor structure to childhood personality that fits well with emerging bio-social theories of personality development. PMID:24932065

Stability and Hopf Bifurcation in a HIV-1 System with Multitime Delays

NASA Astrophysics Data System (ADS)

Zhao, Lingyan; Liu, Haihong; Yan, Fang

In this paper, we propose a mathematical model for HIV-1 infection with three time delays. The model examines a viral-therapy for controlling infections by using an engineered virus to selectively eliminate infected cells. In our model, three time delays represent the latent period of pathogen virus, pathogen virus production period and recombinant (genetically modified) virus production period, respectively. Detailed theoretical analysis have demonstrated that the values of three delays can affect the stability of equilibrium solutions, can also lead to Hopf bifurcation and oscillated solutions of the system. Moreover, we give the conditions for the existence of stable positive equilibrium solution and Hopf bifurcation. Further, the properties of Hopf bifurcation are discussed. These theoretical results indicate that the delays play an important role in determining the dynamic behavior quantitatively. Therefore, it is a fact that delays are very important, which should not be missed in controlling HIV-1 infections.

Enhancing the stability and ecological safety of mass-reared transgenic strains for field release by redundant conditional lethality systems

USDA-ARS?s Scientific Manuscript database

Advances in the genetic manipulation of agriculturally important insects now allows the development of genetic sexing and male sterility systems for more highly efficient biologically-based population control programs, most notably SIT, in fruit pests throughout the world. Potentially, these condit...

The Influence of Parenting on Infant Emotionality: A Multi-Level Psychobiological Perspective

ERIC Educational Resources Information Center

Propper, Cathi; Moore, Ginger, A.

2006-01-01

Infant temperament is theorized to have a strong genetic basis. Yet, studies of the stability of temperament and molecular genetics research on temperament have revealed inconsistent findings. One reason may be because research has not taken into account the influence of early social experiences. We review research on aspects of infant…

Non-mendelian inheritance of SNP markers reveals extensive chromosomal translocations in dioecious hops (humulus lupulus L.)

USDA-ARS?s Scientific Manuscript database

Hop (Humulus lupulus) is a high-climbing, herbaceous perennial, dioecious vine, and has a long history of use as flavoring and stability agent in beer as well as nutraceutical medicine, bio-fuel fermentations and animal fodder. However, the modes of genetic inheritance and genetic diversity are poor...

Regulator of telomere elongation helicase 1 (RTEL1) rs6010620 polymorphism contribute to increased risk of glioma.

PubMed

Zhao, Wei; Bian, Yusong; Zhu, Wei; Zou, Peng; Tang, Guotai

2014-06-01

Regulator of telomere elongation helicase 1 (RTEL1) is critical for genome stability and tumor avoidance. Many studies have reported the associations of RTEL1 rs6010620 with glioma risk, but individually published results were inconclusive. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. The PubMed, Embase, and Web of Science were systematically searched to identify relevant studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were computed to estimate the strength of the association using a fixed or random effects model. Ten studies were eligible for meta-analysis including data on glioma with 6,490 cases and 9,288 controls. Overall, there was a significant association between RTEL1 rs6010620 polymorphism and glioma risk in all four genetic models (GG vs. AA: OR=1.87, 95 % CI=1.60-2.18, P heterogeneity=0.552; GA vs. AA: OR=1.30, 95 % CI=1.16-1.46, P heterogeneity=0.495; dominant model-GG+GA vs. AA: OR=1.46, 95 % CI=1.31-1.63, P heterogeneity=0.528; recessive model-GG vs. GA+AA: OR=1.36, 95 % CI=1.27-1.46, P heterogeneity=0.093). Subgroup analyses by ethnicity showed that RTEL1 rs6010620 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In the stratified analysis by ethnicity and source of controls, significantly increased risk was observed for Asians and Europeans in all genetic models, population-based studies in all genetic models, and hospital-based studies in three genetic models (heterozygote comparison, homozygote comparison, and dominant model). Our meta-analysis suggested that RTEL1 rs6010620 polymorphism is likely to be associated with increased glioma risk, which lends further biological plausibility to these findings.

Simulating bank erosion over an extended natural sinuous river reach using a universal slope stability algorithm coupled with a morphodynamic model

NASA Astrophysics Data System (ADS)

Rousseau, Yannick Y.; Van de Wiel, Marco J.; Biron, Pascale M.

2017-10-01

Meandering river channels are often associated with cohesive banks. Yet only a few river modelling packages include geotechnical and plant effects. Existing packages are solely compatible with single-threaded channels, require a specific mesh structure, derive lateral migration rates from hydraulic properties, determine stability based on friction angle, rely on nonphysical assumptions to describe cutoffs, or exclude floodplain processes and vegetation. In this paper, we evaluate the accuracy of a new geotechnical module that was developed and coupled with Telemac-Mascaret to address these limitations. Innovatively, the newly developed module relies on a fully configurable, universal genetic algorithm with tournament selection that permits it (1) to assess geotechnical stability along potentially unstable slope profiles intersecting liquid-solid boundaries, and (2) to predict the shape and extent of slump blocks while considering mechanical plant effects, bank hydrology, and the hydrostatic pressure caused by flow. The profiles of unstable banks are altered while ensuring mass conservation. Importantly, the new stability module is independent of mesh structure and can operate efficiently along multithreaded channels, cutoffs, and islands. Data collected along a 1.5-km-long reach of the semialluvial Medway Creek, Canada, over a period of 3.5 years are used to evaluate the capacity of the coupled model to accurately predict bank retreat in meandering river channels and to evaluate the extent to which the new model can be applied to a natural river reach located in a complex environment. Our results indicate that key geotechnical parameters can indeed be adjusted to fit observations, even with a minimal calibration effort, and that the model correctly identifies the location of the most severely eroded bank regions. The combined use of genetic and spatial analysis algorithms, in particular for the evaluation of geotechnical stability independently of the hydrodynamic mesh, permits the consideration of biophysical conditions for an extended river reach with complex bank geometries, with only a minor increase in run time. Further improvements with respect to plant representation could assist scientists in better understanding channel-floodplain interactions and in evaluating channel designs in river management projects.

Design of a high altitude long endurance flying-wing solar-powered unmanned air vehicle

NASA Astrophysics Data System (ADS)

Alsahlani, A. A.; Johnston, L. J.; Atcliffe, P. A.

2017-06-01

The low-Reynolds number environment of high-altitude §ight places severe demands on the aerodynamic design and stability and control of a high altitude, long endurance (HALE) unmanned air vehicle (UAV). The aerodynamic efficiency of a §ying-wing configuration makes it an attractive design option for such an application and is investigated in the present work. The proposed configuration has a high-aspect ratio, swept-wing planform, the wing sweep being necessary to provide an adequate moment arm for outboard longitudinal and lateral control surfaces. A design optimization framework is developed under a MATLAB environment, combining aerodynamic, structural, and stability analysis. Low-order analysis tools are employed to facilitate efficient computations, which is important when there are multiple optimization loops for the various engineering analyses. In particular, a vortex-lattice method is used to compute the wing planform aerodynamics, coupled to a twodimensional (2D) panel method to derive aerofoil sectional characteristics. Integral boundary-layer methods are coupled to the panel method in order to predict §ow separation boundaries during the design iterations. A quasi-analytical method is adapted for application to flyingwing con¦gurations to predict the wing weight and a linear finite-beam element approach is used for structural analysis of the wing-box. Stability is a particular concern in the low-density environment of high-altitude flight for flying-wing aircraft and so provision of adequate directional stability and control power forms part of the optimization process. At present, a modified Genetic Algorithm is used in all of the optimization loops. Each of the low-order engineering analysis tools is validated using higher-order methods to provide con¦dence in the use of these computationally-efficient tools in the present design-optimization framework. This paper includes the results of employing the present optimization tools in the design of a HALE, flying-wing UAV to indicate that this is a viable design configuration option.

Growth-rate-dependent dynamics of a bacterial genetic oscillator

NASA Astrophysics Data System (ADS)

Osella, Matteo; Lagomarsino, Marco Cosentino

2013-01-01

Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular “chassis” in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependencies of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality.

Detection and validation of a small broad-host-range plasmid pBBR1MCS-2 for use in genetic manipulation of the extremely acidophilic Acidithiobacillus sp.

PubMed

Hao, Likai; Liu, Xiangmei; Wang, Huiyan; Lin, Jianqun; Pang, Xin; Lin, Jianqiang

2012-09-01

An efficient genetic system for introducing genes into biomining microorganisms is essential not only to experimentally determine the functions of genes predicted based on bioinformatic analysis, but also for their genetic breeding. In this study, a small broad-host-range vector named pBBR1MCS-2, which does not belong to the IncQ, IncW, or IncP groups, was studied for the feasibility of its use in conjugative gene transfer into extremely acidophilic strains of Acidithiobacillus. To do this, a recombinant plasmid pBBR-tac-Sm, a derivative of pBBR1MCS-2, was constructed and the streptomycin resistant gene (Sm(r)) was used as the reporter gene. Using conjugation, pBBR-tac-Sm was successfully transferred into three tested strains of Acidithiobacillus. Then we measured its transfer frequency, its stability in Acidithiobacillus cells, and the level of resistance to streptomycin of the transconjugants and compared this with the IncQ plasmid pJRD215 control. Our results indicate that pBBR1MCS-2 provides a new and useful tool in the genetic manipulation of Acidithiobacillus strains. Copyright © 2012 Elsevier B.V. All rights reserved.

Not All Larvae Stay Close to Home: Insights into Marine Population Connectivity with a Focus on the Brown Surgeonfish (Acanthurus nigrofuscus)

PubMed Central

Eble, Jeff A.; Rocha, Luiz A.; Craig, Matthew T.; Bowen, Brian W.

2014-01-01

Recent reports of localized larval recruitment in predominately small-range fishes are countered by studies that show high genetic connectivity across large oceanic distances. This discrepancy may result from the different timescales over which genetic and demographic processes operate or rather may indicate regular long-distance dispersal in some species. Here, we contribute an analysis of mtDNA cytochrome b diversity in the widely distributed Brown Surgeonfish (Acanthurus nigrofuscus; N = 560), which revealed significant genetic structure only at the extremes of the range (ΦCT = 0.452; P < .001). Collections from Hawaii to the Eastern Indian Ocean comprise one large, undifferentiated population. This pattern of limited genetic subdivision across reefs of the central Indo-Pacific has been observed in a number of large-range reef fishes. Conversely, small-range fishes are often deeply structured over the same area. These findings demonstrate population connectivity differences among species at biogeographic and evolutionary timescales, which likely translates into differences in dispersal ability at ecological and demographic timescales. While interspecific differences in population connectivity complicate the design of management strategies, the integration of multiscale connectivity patterns into marine resource planning will help ensure long-term ecosystem stability by preserving functionally diverse communities. PMID:25505914

Patterns of genetic divergence of three Canarian endemic Lotus (Fabaceae): implications for the conservation of the endangered L. kunkelii.

PubMed

Oliva-Tejera, Felicia; Caujapé-Castells, Juli; Navarro-Déniz, Josefa; Reyes-Betancort, Alfredo; Scholz, Stephan; Baccarani-Rosas, Mario; Cabrera-García, Nereida

2006-08-01

We examined data for 11 allozyme loci in 14 populations that represent the distribution of the endangered Lotus kunkelii, the narrowly distributed L. arinagensis (both endemic to Gran Canaria), and the broad-ranging L. lancerottensis (endemic to the easternmost Canary Islands, Fuerteventura and Lanzarote) to explore and construe patterns of genetic variation and use this data to assess the controversial taxonomic status of L. kunkelii relative to L. lancerottensis. While L. kunkelii maintains low levels of variation, presumably as a consequence of prolonged inbreeding due to very low population size and sharp geographic isolation, the other two taxa have much higher indicators of polymorphism than those reported for other oceanic island endemics. Lotus arinagensis has the highest genetic polymorphism and the lowest interpopulation differentiation, presumably because of its considerable antiquity and habitat stability, despite recent fragmentation. The high interpopulation differentiation in L. lancerottensis is attributed to the Atlantic acting as a barrier, reducing gene flow within islands. Evolutionary analysis of the allozyme evidence indicates that L. kunkelii is genetically closer to L. arinagensis than to L. lancerottensis, thereby dispelling the taxonomic uncertainty and supporting L. kunkelii as a distinct species, warranting legal protection in the forthcoming catalog of threatened Canarian species.

Spaceflight-induced genetic and epigenetic changes in the rice (Oryza sativa L.) genome are independent of each other.

PubMed

Ou, Xiufang; Long, Likun; Wu, Ying; Yu, Yingjie; Lin, Xiuyun; Qi, Xin; Liu, Bao

2010-07-01

An array of studies have reported that the spaceflight environment is mutagenic and may induce phenotypic and genetic changes in diverse organisms. We reported recently that in at least some plant species (e.g., rice) the spaceflight environment can be particularly potent in generating heritable epigenetic changes in the form of altered cytosine methylation patterns and activation of transposable elements. To further study the issue of spaceflight-induced genomic instability, and in particular to test whether the incurred genetic and epigenetic changes are connected or independent of each other, we performed the present study. We subjected seeds of the standard laboratory rice (Oryza sativa L.) cultivar Nipponbare to a spaceflight in the spaceship Long March 2 for 18 days. We then investigated the genetic and DNA methylation stabilities of 11 randomly selected plants germinated from the spaceflown seeds by using two kinds of DNA markers, amplified fragment length polymorphism (AFLP) and methylation sensitive amplified polymorphism (MSAP). For AFLP, by using 15 primer combinations, we assessed 460 genomic loci and found that the frequencies of genetic changes across the 11 plants ranged from 0.7% to 6.7% with an average frequency of 3.5%. For MSAP, by using 14 primer combinations, we assessed 467 loci and detected the occurrence of four major types of cytosine methylation alterations at the CCGG sites, namely CG or CNG hypomethylation and CG or CNG hypermethylation. Collectively, the frequencies of the two kinds of hypermethylation, CG (1.95%) and CNG (1.44%), are about two times higher than those of the two kinds of hypomethylation, CG (0.76%) and CNG (0.80%), though different plants showed variable frequencies for each type of alteration. Further analysis suggested that both the genetic and cytosine methylation changes manifested apparent mutational bias towards specific genomic regions, but the two kinds of instabilities are independent of each other based on correlation analysis.

Demographic stability and high historical connectivity explain the diversity of a savanna tree species in the Quaternary

PubMed Central

Telles, Mariana P. C.; Chaves, Lázaro J.; Lima-Ribeiro, Matheus S.; Collevatti, Rosane G.

2017-01-01

Abstract Background and Aims Cyclic glaciations were frequent throughout the Quaternary and this affected species distribution and population differentiation worldwide. The present study reconstructed the demographic history and dispersal routes of Eugenia dysenterica lineages and investigated the effects of Quaternary climate change on its spatial pattern of genetic diversity. Methods A total of 333 individuals were sampled from 23 populations and analysed by sequencing four regions of the chloroplast DNA and the internal transcribed spacer of the nuclear DNA. The analyses were performed using a multi-model inference approach based on ecological niche modelling and statistical phylogeography. Key Results Coalescent simulation showed that population stability through time is the most likely scenario. The palaeodistribution dynamics predicted by the ecological niche models revealed that the species was potentially distributed across a large area, extending over Central-Western Brazil through the last glaciation. The lineages of E. dysenterica dispersed from Central Brazil towards populations at the northern, western and south-eastern regions. A historical refugium through time may have favoured lineage dispersal and the maintenance of genetic diversity. Conclusions The results suggest that the central region of the Cerrado biome is probably the centre of distribution of E. dysenterica and that the spatial pattern of its genetic diversity may be the outcome of population stability throughout the Quaternary. The lower genetic diversity in populations in the south-eastern Cerrado biome is probably due to local climatic instability during the Quaternary. PMID:28115317

A meta-analysis of heritability of cognitive aging: minding the "missing heritability" gap.

PubMed

Reynolds, Chandra A; Finkel, Deborah

2015-03-01

The etiologies underlying variation in adult cognitive performance and cognitive aging have enjoyed much attention in the literature, but much of that attention has focused on broad factors, principally general cognitive ability. The current review provides meta-analyses of age trends in heritability of specific cognitive abilities and considers the profile of genetic and environmental factors contributing to cognitive aging to address the 'missing heritability' issue. Our findings, based upon evaluating 27 reports in the literature, indicate that verbal ability demonstrated declining heritability, after about age 60, as did spatial ability and perceptual speed more modestly. Trends for general memory, working memory, and spatial ability generally indicated stability, or small increases in heritability in mid-life. Equivocal results were found for executive function. A second meta-analysis then considered the gap between twin-based versus SNP-based heritability derived from population-based GWAS studies. Specifically, we considered twin correlation ratios to agnostically re-evaluate biometrical models across age and by cognitive domain. Results modestly suggest that nonadditive genetic variance may become increasingly important with age, especially for verbal ability. If so, this would support arguments that lower SNP-based heritability estimates result in part from uncaptured non-additive influences (e.g., dominance, gene-gene interactions), and possibly gene-environment (GE) correlations. Moreover, consistent with longitudinal twin studies of aging, as rearing environment becomes a distal factor, increasing genetic variance may result in part from nonadditive genetic influences or possible GE correlations. Sensitivity to life course dynamics is crucial to understanding etiological contributions to adult cognitive performance and cognitive aging.

Stability and change in etiological factors for alcohol use disorder and major depression.

PubMed

Torvik, Fartein Ask; Rosenström, Tom Henrik; Ystrom, Eivind; Tambs, Kristian; Røysamb, Espen; Czajkowski, Nikolai; Gillespie, Nathan; Knudsen, Gun Peggy; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-08-01

Alcohol use disorder (AUD) and major depressive disorder (MDD) are often comorbid. It is not understood how genetic risk factors for these disorders relate to each other over time and to what degree they are stable. Age-dependent characteristics of the disorders indicate that different genetic factors could be relevant at different stages of life, and MDD may become increasingly correlated with AUD over time. DSM-IV diagnoses of AUD and MDD were assessed by interviews of 2,801 young adult twins between 1999 and 2004 (T1) and 2,284 of the same twins between 2010 and 2011 (T2). Stability, change, and covariation were investigated in longitudinal biometric models. New genetic factors explained 56.4% of the genetic variance in AUD at T2. For MDD, there was full overlap between genetic influences at T1 and T2. Genetic risk factors for MDD were related to AUD, but their association with AUD did not increase over time. Thus, genetic risk factors for AUD, but not MDD, vary with age, suggesting that AUD has age-dependent heritable etiologies. Molecular genetic studies of AUD may therefore benefit from stratifying by age. The new genetic factors in AUD were not related to MDD. Environmental influences on the 2 disorders were correlated in middle, but not in young adulthood. The environmental components for AUD correlated over time (r = .27), but not for MDD. Environmental influences on AUD can have long-lasting effects, and the effects of preventive efforts may be enduring. Environment influences seem to be largely transient. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.

PubMed

Kogan, Valeria; Molodtsov, Ivan; Menshikov, Leonid I; Shmookler Reis, Robert J; Fedichev, Peter

2015-08-28

Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals.

AFLP-based genetic diversity and its comparison with diversity based on SSR, SAMPL, and phenotypic traits in bread wheat.

PubMed

Roy, J K; Lakshmikumaran, M S; Balyan, H S; Gupta, P K

2004-02-01

Data on AFLP (eight primer pairs) and 14 phenotypic traits, collected on 55 elite and exotic bread wheat genotypes, were utilized for estimations of genetic diversity. We earlier used these 55 genotypes for a similar study using SSRs and SAMPL. As many as 615 scorable AFLP bands visualized included 287 (46.6%) polymorphic bands. The phenotypic traits included yield and its component traits, as well as physiomorphological traits like flag leaf area. Dendrograms were prepared using cluster analysis based on Jaccard's similarity coefficients in case of AFLP and on squared Euclidean distances in case of phenotypic traits. PCA was conducted using AFLP data and a PCA plot was prepared, which was compared with clustering patterns in two dendrograms, one each for AFLP and phenotypic traits. The results were also compared with published results that included studies conducted elsewhere using entirely different wheat germplasm and our own SSR and SAMPL studies based on the same 55 genotypes used in the present study. It was shown that molecular markers are superior to phenotypic traits and that AFLP and SAMPL are superior to other molecular markers for estimation of genetic diversity. On the basis of AFLP analysis and keeping in view the yield performance and stability, a pair of genotypes (E3876 and E677) was recommended for hybridization in order to develop superior cultivars.

Population structure of Cicada barbara Stål (Hemiptera, Cicadoidea) from the Iberian Peninsula and Morocco based on mitochondrial DNA analysis.

PubMed

Pinto-Juma, G A; Quartau, J A; Bruford, M W

2008-02-01

We assess the genetic history and population structure of Cicada barbara in Morocco and the Iberian Peninsula, based on analysis of the mitochondrial cytochrome b gene. The divergence between Morocco and the Iberian Peninsula populations was strongly corroborated by the molecular data, suggesting genetically isolated populations with a low level of gene flow. The Ceuta population from Spanish North Africa was more similar to the Iberian populations than the surrounding Moroccan populations, suggesting that the Strait of Gibraltar has not been acting as a strict barrier to dispersal while the Rif Mountains have. The Iberian Peninsula specimens showed a signature of demographic expansion before that which occurred in Morocco, but some of the assumptions related to the demographic parameters should be considered with caution due to the small genetic variation found. The high haplotype diversity found in Morocco implies higher demographic stability than in the Iberian Peninsula populations. These results do not, however, suggest a Moroccan origin for Iberian cicadas; but the most northwest region in Africa, such as Ceuta, might have acted as a southern refuge for Iberian cicadas during the most severe climatic conditions, from where they could expand north when climate improved. The separation of two subspecies within C. barbara (C. barbara lusitanica and C. barbara barbara) finds support with these results.

Effects of Holding Time, Storage, and the Preservation of ...

EPA Pesticide Factsheets

The purpose of this project was to answer questions related to storage of samples to be analyzed by the quantitative polymerase chain reaction (qPCR)-based assays for fecal indicator bacteria. The project was divided into two parts. The first part was to determine if filters that were used to collect fecal indicators could be stored frozen and analyzed at a later date and the second part was to determine if refrigerated water samples could be held for 24 to 48 hours prior to analysis by qPCR. Both of these studies answer questions that were important in the analysis of fresh and marine surface water samples for beach monitoring purposes. 1) Develop and evaluate qPCR assays and test methods for the detection and quantification of genetic markers from indicator bacteria that are associated with human fecal waste and from two new groups of general fecal indicator bacteria (E. coli and Clostridia) that historically have been widely used or are favored in specific regions 2) Determine the occurrence and densities of genetic markers detected by new qPCR assays developed under objective 1 and compare with occurrence and densities of genetic markers detected by previously developed qPCR assays for enterococci and total Bacterioidalesin waste waters and fecal material from different animal sources. 3) Determine stability of fecal indicator bacteria target DNA sequences in freezer archived filter retentates of ambient surface water samples 4) Determine the densitie

Stability indicating methods for the analysis of cefprozil in the presence of its alkaline induced degradation product

NASA Astrophysics Data System (ADS)

Attia, Khalid A. M.; Nassar, Mohammed W. I.; El-Zeiny, Mohamed B.; Serag, Ahmed

2016-04-01

Three simple, specific, accurate and precise spectrophotometric methods were developed for the determination of cefprozil (CZ) in the presence of its alkaline induced degradation product (DCZ). The first method was the bivariate method, while the two other multivariate methods were partial least squares (PLS) and spectral residual augmented classical least squares (SRACLS). The multivariate methods were applied with and without variable selection procedure (genetic algorithm GA). These methods were tested by analyzing laboratory prepared mixtures of the above drug with its alkaline induced degradation product and they were applied to its commercial pharmaceutical products.

Selection of common bean genotypes for the Cerrado/Pantanal ecotone via mixed models and multivariate analysis.

PubMed

Corrêa, A M; Pereira, M I S; de Abreu, H K A; Sharon, T; de Melo, C L P; Ito, M A; Teodoro, P E; Bhering, L L

2016-10-17

The common bean, Phaseolus vulgaris, is predominantly grown on small farms and lacks accurate genotype recommendations for specific micro-regions in Brazil. This contributes to a low national average yield. The aim of this study was to use the methods of the harmonic mean of the relative performance of genetic values (HMRPGV) and the centroid, for selecting common bean genotypes with high yield, adaptability, and stability for the Cerrado/Pantanal ecotone region in Brazil. We evaluated 11 common bean genotypes in three trials carried out in the dry season in Aquidauana in 2013, 2014, and 2015. A likelihood ratio test detected a significant interaction between genotype x year, contributing 54% to the total phenotypic variation in grain yield. The three genotypes selected by the joint analysis of genotypic values in all years (Carioca Precoce, BRS Notável, and CNFC 15875) were the same as those recommended by the HMRPGV method. Using the centroid method, genotypes BRS Notável and CNFC 15875 were considered ideal genotypes based on their high stability to unfavorable environments and high responsiveness to environmental improvement. We identified a high association between the methods of adaptability and stability used in this study. However, the use of centroid method provided a more accurate and precise recommendation of the behavior of the evaluated genotypes.

Reference genes for reverse transcription quantitative PCR in canine brain tissue.

PubMed

Stassen, Quirine E M; Riemers, Frank M; Reijmerink, Hannah; Leegwater, Peter A J; Penning, Louis C

2015-12-09

In the last decade canine models have been used extensively to study genetic causes of neurological disorders such as epilepsy and Alzheimer's disease and unravel their pathophysiological pathways. Reverse transcription quantitative polymerase chain reaction is a sensitive and inexpensive method to study expression levels of genes involved in disease processes. Accurate normalisation with stably expressed so-called reference genes is crucial for reliable expression analysis. Following the minimum information for publication of quantitative real-time PCR experiments precise guidelines, the expression of ten frequently used reference genes, namely YWHAZ, HMBS, B2M, SDHA, GAPDH, HPRT, RPL13A, RPS5, RPS19 and GUSB was evaluated in seven brain regions (frontal lobe, parietal lobe, occipital lobe, temporal lobe, thalamus, hippocampus and cerebellum) and whole brain of healthy dogs. The stability of expression varied between different brain areas. Using the GeNorm and Normfinder software HMBS, GAPDH and HPRT were the most reliable reference genes for whole brain. Furthermore based on GeNorm calculations it was concluded that as little as two to three reference genes are sufficient to obtain reliable normalisation, irrespective the brain area. Our results amend/extend the limited previously published data on canine brain reference genes. Despite the excellent expression stability of HMBS, GAPDH and HRPT, the evaluation of expression stability of reference genes must be a standard and integral part of experimental design and subsequent data analysis.

[The absence of cyclin-dependent protein kinase Pho85 affects stability of mitochondrial DNA in yeast Saccharomyces cerevisiae].

PubMed

Fizikova, A Iu; Padkina, M V; Sambuk, E V

2009-06-01

The cyclin-dependent protein kinase Pho85 is involved in the regulation of phosphate metabolism in yeast Saccharomyces cerevisiae. Mutations in the PH085 gene lead to constitutive synthesis of Pho5 acidic phosphatase, a delay in cell growth on media containing nonfermentable carbon sources, and other pleiotropic effects. In this work, it was shown that the accumulation of respiratory incompetent cells occurs with high frequency in strains carrying pho85 mutations as early as during the first cell divisions, and the number of these cells at the early logarithmic growth phase of the culture promptly reaches virtually 100%. Cytological analysis revealed a high accumulation rate of [rho(0)] cells the background of gene pho85 that may be related to disturbances in the distribution of mitochondrial nucleoids rather than to changes in morphology of mitochondria and a delay in their transport into the bud. Genetic analysis revealed that the appearing secondary mutations pho4, pho81, pho84, and pho87 stabilize nucleoids and hamper the loss of mitochondrial DNA caused by pho85. These results provide evidence for the influence of intracellular phosphate concentration on the inheritance of mitochondrial nucleoids, but it is fully probable that the occurrence of mutation pho4 in the background of gene pho85 may change the expression level of other genes required for the stabilization of mitochondrial functions.

A periodic table for cancer.

PubMed

Epstein, Richard J

2015-01-01

Cancers exhibit differences in metastatic behavior and drug sensitivity that correlate with certain tumor-specific variables such as differentiation grade, growth rate/extent and molecular regulatory aberrations. In practice, patient management is based on the past results of clinical trials adjusted for these biomarkers. Here, it is proposed that treatment strategies could be fine-tuned upfront simply by quantifying tumorigenic spatial (cell growth) and temporal (genetic stability) control losses, as predicted by genetic defects of cell-cycle-regulatory gatekeeper and genome-stabilizing caretaker tumor suppressor genes, respectively. These differential quantifications of tumor dysfunction may in turn be used to create a tumor-specific 'periodic table' that guides rational formulation of survival-enhancing anticancer treatment strategies.

Rapid in vitro propagation, conservation and analysis of genetic stability of Viola pilosa.

PubMed

Soni, Madhvi; Kaur, Rajinder

2014-01-01

A protocol for in vitro propagation was developed for Viola pilosa, a plant of immense medicinal value. To start with in vitro propagation, the sterilized explants (buds) were cultured on MS basal medium supplemented with various concentrations of growth regulators. One of the medium compositions MS basal + 0.5 mg/l BA + 0.5 mg/l TDZ + 0.5 mg/l GA3 gave best results for in vitro shoot bud establishment. Although the problem of shoot vitrification occurred on this medium but this was overcome by transferring the vitrified shoots on MS medium supplemented with 1 mg/l BA and 0.25 mg/l Kn. The same medium was found to be the best medium for further in vitro shoot multiplication. 100 % root induction from in vitro grown shoots was obtained on half strength MS medium supplemented with 1 mg/l IBA. In vitro formed plantlets were hardened and transferred to soil with 83 % survival. Additionally, conservation of in vitro multiplying shoots was also attempted using two different approaches namely slowing down the growth at low temperature and cryopreservation following vitrification. At low temperature retrieval rate was better at 10 °C than at 4 °C after conservation of in vitro multiplying shoots. In cryopreservation-vitrification studies, the vitrified shoot buds gave maximum retrieval of 41.66 % when they were precooled at 4 °C, while only 16.66 % vitrified shoots were retrieved from those precooled at 10 °C. Genetic stability of the in vitro grown plants was analysed by RAPD and ISSR markers which indicated no somaclonal variation among in vitro grown plants demonstrating the feasibility of using the protocol without any adverse genetical effects.

Evidence of susceptibility to lamivudine-based HAART and genetic stability of hepatitis B virus (HBV) in HIV co-infected patients: A South African longitudinal HBV whole genome study.

PubMed

Amponsah-Dacosta, Edina; Rakgole, J Nare; Gededzha, Maemu P; Lukhwareni, Azwidowi; Blackard, Jason T; Selabe, Selokela G; Mphahlele, M Jeffrey

2016-09-01

Reports on the concomitant impact of HIV co-infection and long term highly active anti-retroviral therapy (HAART) on the genetic stability and molecular evolution of HBV are limited in sub-Saharan Africa. This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infected patients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infected patients, consecutively recruited and followed-up, were screened for hepatitis B serological markers, and their viral loads determined. The HBV genome was amplified from longitudinal samples and characterized by Bayesian inference, mutational analysis, and identification of immune selection pressure. All patients exhibited persistent chronic HBV infection at baseline, as well as over the course of follow-up despite exposure to 3TC-based HAART. The polymerase gene in all isolates was relatively variable prior to HAART initiation at baseline and during the course of follow-up, although primary drug resistance mutations were not detected. All but one patient were infected with HBV subgenotype A1. The divergence rates between baseline and the last follow-up sequences ranged from 0 to 2.0×10(-3) substitutions per site per year (s/s/y). Positive selection pressure was evident within the surface and core genes. Despite persistent HBV infection in the HIV co-infected patients exposed to long term 3TC-based HAART, the molecular evolution of HBV over a 5year period was unremarkable. In addition, HBV exhibited minimal genetic variability overtime. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluorescence-based characterization of genetically encoded peptides that fold in live cells: progress toward a generic hairpin scaffold

NASA Astrophysics Data System (ADS)

Cheng, Zihao; Campbell, Robert E.

2007-02-01

Binding proteins suitable for expression and high affinity molecular recognition in the cytoplasm or nucleus of live cells have numerous applications in the biological sciences. In an effort to add a new minimal motif to the growing repertoire of validated non-immunoglobulin binding proteins, we have undertaken the development of a generic protein scaffold based on a single β-hairpin that can fold efficiently in the cytoplasm. We have developed a method, based on the measurement of fluorescence resonance energy transfer (FRET) between a genetically fused cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP), that allows the structural stability of recombinant β-hairpin peptides to be rapidly assessed both in vitro and in vivo. We have previously reported the validation of this method when applied to a 16mer tryptophan zipper β-hairpin. We now describe the use of this method to evaluate the potential of a designed 20mer β-hairpin peptide with a 3rd Trp/Trp cross-strand pair to function as a generic protein scaffold. Quantitative analysis of the FRET efficiency, resistance to proteolysis (assayed by loss of FRET), and circular dichroism spectra revealed that the 20mer peptide is significantly more tolerant of destabilizing mutations than the 16mer peptide. Furthermore, we experimentally demonstrate that the in vitro determined β-hairpin stabilities are well correlated with in vivo β-hairpin stabilities as determined by FRET measurements of colonies of live bacteria expressing the recombinant peptides flanked by CFP and YFP. Finally, we report on our progress to develop highly folded 24mer and 28mer β-hairpin peptides through the use of fluorescence-based library screening.

The evolutionary stability of cross-sex, cross-trait genetic covariances.

PubMed

Gosden, Thomas P; Chenoweth, Stephen F

2014-06-01

Although knowledge of the selective agents behind the evolution of sexual dimorphism has advanced considerably in recent years, we still lack a clear understanding of the evolutionary durability of cross-sex genetic covariances that often constrain its evolution. We tested the relative stability of cross-sex genetic covariances for a suite of homologous contact pheromones of the fruit fly Drosophila serrata, along a latitudinal gradient where these traits have diverged in mean. Using a Bayesian framework, which allowed us to account for uncertainty in all parameter estimates, we compared divergence in the total amount and orientation of genetic variance across populations, finding divergence in orientation but not total variance. We then statistically compared orientation divergence of within-sex (G) to cross-sex (B) covariance matrices. In line with a previous theoretical prediction, we find that the cross-sex covariance matrix, B, is more variable than either within-sex G matrix. Decomposition of B matrices into their symmetrical and nonsymmetrical components revealed that instability is linked to the degree of asymmetry. We also find that the degree of asymmetry correlates with latitude suggesting a role for spatially varying natural selection in shaping genetic constraints on the evolution of sexual dimorphism. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency.

PubMed

Turton, J P; Strom, M; Langham, S; Dattani, M T; Le Tissier, P

2012-03-01

  Mutations in the POU1F1 gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).   The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.   We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin-like growth factor 1 (IGF1), with normal random cortisol.   The POU1F1 coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and in vitro assays.   Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in POU1F1: a transition at position +3 of intron 1 [IVS1+3nt(A>G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A>G) results in a reduction in the correctly spliced POU1F1 mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1(R265W) revealed complete loss of function resulting from severely reduced protein stability.   Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A>G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy. © 2012 Blackwell Publishing Ltd.

Are genetically robust regulatory networks dynamically different from random ones?

NASA Astrophysics Data System (ADS)

Sevim, Volkan; Rikvold, Per Arne

We study a genetic regulatory network model developed to demonstrate that genetic robustness can evolve through stabilizing selection for optimal phenotypes. We report preliminary results on whether such selection could result in a reorganization of the state space of the system. For the chosen parameters, the evolution moves the system slightly toward the more ordered part of the phase diagram. We also find that strong memory effects cause the Derrida annealed approximation to give erroneous predictions about the model's phase diagram.

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues

PubMed Central

Anderson, Matthew Z.; Porman, Allison M.; Wang, Na; Mancera, Eugenio; Bennett, Richard J.

2016-01-01

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming. PMID:27711197

Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes.

PubMed

Sun, Honghe; Wu, Shan; Zhang, Guoyu; Jiao, Chen; Guo, Shaogui; Ren, Yi; Zhang, Jie; Zhang, Haiying; Gong, Guoyi; Jia, Zhangcai; Zhang, Fan; Tian, Jiaxing; Lucas, William J; Doyle, Jeff J; Li, Haizhen; Fei, Zhangjun; Xu, Yong

2017-10-09

The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima × C. moschata interspecific F 1 hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Synthetic gene circuits for metabolic control: design trade-offs and constraints

PubMed Central

Oyarzún, Diego A.; Stan, Guy-Bart V.

2013-01-01

A grand challenge in synthetic biology is to push the design of biomolecular circuits from purely genetic constructs towards systems that interface different levels of the cellular machinery, including signalling networks and metabolic pathways. In this paper, we focus on a genetic circuit for feedback regulation of unbranched metabolic pathways. The objective of this feedback system is to dampen the effect of flux perturbations caused by changes in cellular demands or by engineered pathways consuming metabolic intermediates. We consider a mathematical model for a control circuit with an operon architecture, whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We address the existence and stability of the steady state, the dynamic response of the network under perturbations, and their dependence on common tuneable knobs such as the promoter characteristic and ribosome binding site (RBS) strengths. Our analysis reveals trade-offs between the steady state of the enzymes and the intermediates, together with a separation principle between promoter and RBS design. We show that enzymatic saturation imposes limits on the parameter design space, which must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. The use of promoters with a broad dynamic range and a small leaky expression enlarges the design space. Simulation results with realistic parameter values also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations. PMID:23054953

Design and Management of Field Trials of Transgenic Cereals

NASA Astrophysics Data System (ADS)

Bedő, Zoltán; Rakszegi, Mariann; Láng, László

The development of gene transformation systems has allowed the introgression of alien genes into plant genomes, thus providing a mechanism for broadening the genetic resources available to plant breeders. The design and the management of field trials vary according to the purpose for which transgenic cereals are developed. Breeders study the phenotypic and genotypic stability of transgenic plants, monitor the increase in homozygosity of transgenic genotypes under field conditions, and develop backcross generations to transfer the introduced genes into secondary transgenic cereal genotypes. For practical purposes, they may also multiply seed of the transgenic lines to produce sufficient amounts of grain for the detailed analysis of trait(s) of interest, to determine the field performance of transgenic lines, and to compare them with the non-transformed parental genotypes. Prior to variety registration, the Distinctness, Uniformity and Stability (DUS) tests and Value for Cultivation and Use (VCU) experiments are carried out in field trials. Field testing includes specific requirements for transgenic cereals to assess potential environmental risks. The capacity of the pollen to survive, establish and disseminate in the field test environment, the potential for gene transfer, the effects of products expressed by the introduced sequences and phenotypic and genotypic instability that might cause deleterious effects must all be specifically monitored, as required by EU Directives 2003/701/EC (1) on the release of genetically modified higher plants in the environment.

Production stability of active polysaccharides of Dendrobium huoshanense using long-term cultures of protocorm-like bodies.

PubMed

Zha, Xue-Qiang; Luo, Jian-Ping

2008-01-01

In this study, the production stability of active polysaccharides in protocorm-like bodies (PLBs) induced from the seedling segments of Dendrobium huoshanense C. Z. Tang et S. J. Cheng was investigated during long-term subculture. Subcultures were conducted once every 30 days. With an average inoculum of 39 g/L fresh PLBs, the increase in biomass ranged from 95.7 g/L to 103.9 g/L in fresh weight and 3.2 g/L to 3.4 g/L in dry weight during eighteen continuous subcultures while polysaccharide content in PLBs was from 0.8 mg/g Fw (mg polysaccharide per gram PLBs in fresh weight) to 1.0 mg/g Fw. In addition, polysaccharides from all cultures showed a similar potential of stimulating interferon gamma (IFN-gamma) release in the supernatant of splenocytes and tumor necrosis factor alpha (TNF-alpha) release in the supernatant of peritoneal macrophages. To elucidate the genetic basis of polysaccharide production stability in long-term subculture of PLBs, the genetic fingerprints by RAPD were further analyzed using plantlets from PLB development. Results showed that there is no evidence of genetic variation both within the plantlets from the different subcultures of PLBs and between long-term subcultures and the donor plants.

Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

PubMed

Steiger, S; Capodeanu-Nägler, A; Gershman, S N; Weddle, C B; Rapkin, J; Sakaluk, S K; Hunt, J

2015-12-01

Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Demographic and genetic status of an isolated population of bog turtles (Glyptemys muhlenbergii): Implications for managing small populations of long-lived animals

USGS Publications Warehouse

Pittman, Shannon E.; King, T.L.; Faurby, S.; Dorcas, M.E.

2011-01-01

In this study, we sought to determine the population stability and genetic diversity of one isolated population of the federally-threatened bog turtle (Glyptemys muhlenbergii) in North Carolina. Using capture-recapture data, we estimated adult survival and population growth rate from 1992 to 2007. We found that the population decreased from an estimated 36 adult turtles in 1994 to approximately 11 adult turtles in 2007. We found a constant adult survival of 0. 893 (SE = 0. 018, 95% confidence interval, 0. 853-0. 924) between 1992 and 2007. Using 18 microsatellite markers, we compared the genetic status of this population with five other bog turtle populations. The target population displayed allelic richness (4. 8 ?? 0. 5) and observed heterozygosity (0. 619 ?? 0. 064) within the range of the other bog turtle populations. Coalescent analysis of population growth rate, effective population size, and timing of population structuring event also indicated the genetics of the target population were comparable to the other populations studied. Estimates of effective population size were a proportion of the census size in all populations except the target population, in which the effective population size was larger than the census size (30 turtles vs. 11 turtles). We attribute the high genetic diversity in the target population to the presence of multiple generations of old turtles. This study illustrates that the demographic status of populations of long-lived species may not be reflected genetically if a decline occurred recently. Consequently, the genetic integrity of populations of long-lived animals experiencing rapid demographic bottlenecks may be preserved through conservation efforts effective in addressing demographic problems. ?? 2011 Springer Science+Business Media B.V.

Determination of the mechanical parameters of rock mass based on a GSI system and displacement back analysis

NASA Astrophysics Data System (ADS)

Kang, Kwang-Song; Hu, Nai-Lian; Sin, Chung-Sik; Rim, Song-Ho; Han, Eun-Cheol; Kim, Chol-Nam

2017-08-01

It is very important to obtain the mechanical paramerters of rock mass for excavation design, support design, slope design and stability analysis of the underground structure. In order to estimate the mechanical parameters of rock mass exactly, a new method of combining a geological strength index (GSI) system with intelligent displacment back analysis is proposed in this paper. Firstly, average spacing of joints (d) and rock mass block rating (RBR, a new quantitative factor), surface condition rating (SCR) and joint condition factor (J c) are obtained on in situ rock masses using the scanline method, and the GSI values of rock masses are obtained from a new quantitative GSI chart. A correction method of GSI value is newly introduced by considering the influence of joint orientation and groundwater on rock mass mechanical properties, and then value ranges of rock mass mechanical parameters are chosen by the Hoek-Brown failure criterion. Secondly, on the basis of the measurement result of vault settlements and horizontal convergence displacements of an in situ tunnel, optimal parameters are estimated by combination of genetic algorithm (GA) and numerical simulation analysis using FLAC3D. This method has been applied in a lead-zinc mine. By utilizing the improved GSI quantization, correction method and displacement back analysis, the mechanical parameters of the ore body, hanging wall and footwall rock mass were determined, so that reliable foundations were provided for mining design and stability analysis.

Drift, selection, or migration? Processes affecting genetic differentiation and variation along a latitudinal gradient in an amphibian.

PubMed

Cortázar-Chinarro, Maria; Lattenkamp, Ella Z; Meyer-Lucht, Yvonne; Luquet, Emilien; Laurila, Anssi; Höglund, Jacob

2017-08-14

Past events like fluctuations in population size and post-glacial colonization processes may influence the relative importance of genetic drift, migration and selection when determining the present day patterns of genetic variation. We disentangle how drift, selection and migration shape neutral and adaptive genetic variation in 12 moor frog populations along a 1700 km latitudinal gradient. We studied genetic differentiation and variation at a MHC exon II locus and a set of 18 microsatellites. Using outlier analyses, we identified the MHC II exon 2 (corresponding to the β-2 domain) locus and one microsatellite locus (RCO8640) to be subject to diversifying selection, while five microsatellite loci showed signals of stabilizing selection among populations. STRUCTURE and DAPC analyses on the neutral microsatellites assigned populations to a northern and a southern cluster, reflecting two different post-glacial colonization routes found in previous studies. Genetic variation overall was lower in the northern cluster. The signature of selection on MHC exon II was weaker in the northern cluster, possibly as a consequence of smaller and more fragmented populations. Our results show that historical demographic processes combined with selection and drift have led to a complex pattern of differentiation along the gradient where some loci are more divergent among populations than predicted from drift expectations due to diversifying selection, while other loci are more uniform among populations due to stabilizing selection. Importantly, both overall and MHC genetic variation are lower at northern latitudes. Due to lower evolutionary potential, the low genetic variation in northern populations may increase the risk of extinction when confronted with emerging pathogens and climate change.

Structure and stability of genetic variance-covariance matrices: A Bayesian sparse factor analysis of transcriptional variation in the three-spined stickleback.

PubMed

Siren, J; Ovaskainen, O; Merilä, J

2017-10-01

The genetic variance-covariance matrix (G) is a quantity of central importance in evolutionary biology due to its influence on the rate and direction of multivariate evolution. However, the predictive power of empirically estimated G-matrices is limited for two reasons. First, phenotypes are high-dimensional, whereas traditional statistical methods are tuned to estimate and analyse low-dimensional matrices. Second, the stability of G to environmental effects and over time remains poorly understood. Using Bayesian sparse factor analysis (BSFG) designed to estimate high-dimensional G-matrices, we analysed levels variation and covariation in 10,527 expressed genes in a large (n = 563) half-sib breeding design of three-spined sticklebacks subject to two temperature treatments. We found significant differences in the structure of G between the treatments: heritabilities and evolvabilities were higher in the warm than in the low-temperature treatment, suggesting more and faster opportunity to evolve in warm (stressful) conditions. Furthermore, comparison of G and its phenotypic equivalent P revealed the latter is a poor substitute of the former. Most strikingly, the results suggest that the expected impact of G on evolvability-as well as the similarity among G-matrices-may depend strongly on the number of traits included into analyses. In our results, the inclusion of only few traits in the analyses leads to underestimation in the differences between the G-matrices and their predicted impacts on evolution. While the results highlight the challenges involved in estimating G, they also illustrate that by enabling the estimation of large G-matrices, the BSFG method can improve predicted evolutionary responses to selection. © 2017 John Wiley & Sons Ltd.

Feasibility for improving phytonutrient content in vegetable crops using conventional breeding strategies: case study with carotenoids and tocopherols in sweet corn and broccoli.

PubMed

Ibrahim, Khalid E; Juvik, John A

2009-06-10

Among vegetables, sweet corn ( Zea mays L.) and broccoli ( Brassica oleracea L. ssp. italica) are important sources of dietary carotenoids and tocopherols. Because medical evidence suggests that carotenoid and tocopherol health-promoting activity acts in a dose-dependent manner, conventional breeding to develop elite sweet corn and broccoli germplasm with enhanced levels of these phytochemicals will potentially promote health among the consuming public. This investigation includes the quantitative analysis of carotenoid and tocopherol contents of 41 corn and 24 broccoli genotypes grown in multiple environments (years and seasons in one location) to partition the variation into genetic, environment, and genotype by environment interaction (GxE) components and measure the phenotypic stability of genotypes for these phytochemicals. The primary carotenoids and tocopherols in corn were lutein and gamma-tocopherol (65 and 73% of total carotenoid and tocopherol, respectively), whereas beta-carotene and alpha-tocopherol were dominant in broccoli (65 and 79% of total carotenoid and tocopherol, respectively). Partitioning of the variance indicated that genetic differences among the genotypes averaged for the primary compounds in corn (lutein, zeaxanthin, and alpha- and gamma-tocopherol) and broccoli (beta-carotene, lutein, and alpha- and gamma-tocopherol) accounted for the largest proportion of the variation (67 and 55% of total phenotypic variation averaged across the phytochemicals in sweet corn and broccoli, respectively). Stability analysis identified several corn (IL451b sh2 and IL2027-8 sh2) and broccoli ('Pirate' and 'Baccus') genotypes with relatively high mean concentrations for the various carotenoids and tocopherols that were comparatively stable across seasons and years. The results of this investigation suggest that sweet corn and broccoli germplasm with enhanced concentrations of carotenoids and tocopherols can be developed using conventional breeding protocols.

Production and characterization of genetically modified human IL-11 variants.

PubMed

Sano, Emiko; Takei, Toshiaki; Ueda, Takuya; Tsumoto, Kouhei

2017-02-01

Interleukin-11 (IL-11) has been expected as a drug on severe thrombocytopenia caused by myelo-suppressive chemotherapy. Whereas, development of IL-11 inhibitor is also expected for a treatment against IL-11 related cancer progression. Here, we will demonstrate the creation of various kinds of genetically modified hIL-11s. Modified vectors were constructed by introducing N- or O-glycosylation site on the region of hIL-11 that does not belong to the core α-helical motif based on the predicted secondary structure. N-terminal (N: between 22 to 23 aa), the first loop (M1:70 to 71 aa), the second loop (M2:114-115 aa), the third loop (M3:160-161 aa) and C-terminal (C: 200- aa) were selected for modification. A large scale production system was established and the characteristics of modified hIL-11s were evaluated. The structure was analyzed by amino acid sequence and composition analysis and CD-spectra. Glycan was assessed by monosaccharide composition analysis. Growth promoting activity and biological stability were analyzed by proliferation of T1165 cells. N-terminal modified proteins were well glycosylated and produced. Growth activity of 3NN with NASNASNAS sequence on N-terminal was about tenfold higher than wild type (WT). Structural and biological stabilities of 3NN were also better than WT and residence time in mouse blood was longer than WT. M1 variants lacked growth activity though they are well glycosylated and secondary structure is very stable. Both of 3NN and OM1 with AAATPAPG on M1 associated with hIL-11R strongly. These results indicate N-terminal and M1 variants will be expected for practical use as potent agonists or antagonists of hIL-11. Copyright © 2016 Elsevier B.V. All rights reserved.

A meta-analysis of the associations between common variation in the PDE8B gene and thyroid hormone parameters, including assessment of longitudinal stability of associations over time and effect of thyroid hormone replacement

PubMed Central

Taylor, Peter N; Panicker, Vijay; Sayers, Adrian; Shields, Beverley; Iqbal, Ahmed; Bremner, Alexandra P; Beilby, John P; Leedman, Peter J; Hattersley, Andrew T; Vaidya, Bijay; Frayling, Timothy; Evans, Jonathan; Tobias, Jonathan H; Timpson, Nicholas J; Walsh, John P; Dayan, Colin M

2011-01-01

Objective Common variants in PDE8B are associated with TSH but apparently without any effect on thyroid hormone levels that is difficult to explain. Furthermore, the stability of the association has not been examined in longitudinal studies or in patients on levothyroxine (l-T4). Design Totally, four cohorts were used (n=2557): the Busselton Health Study (thyroid function measured on two occasions), DEPTH, EFSOCH (selective cohorts), and WATTS (individuals on l-T4). Methods Meta-analysis to clarify associations between the rs4704397 single nucleotide polymorphism in PDE8B on TSH, tri-iodothyronine (T3), and T4 levels. Results Meta-analysis confirmed that genetic variation in PDE8B was associated with TSH (P=1.64×10−10 0.20 s.d./allele, 95% confidence interval (CI) 0.142, 0.267) and identified a possible new association with free T4 (P=0.023, −0.07 s.d./allele, 95% CI −0.137, −0.01), no association was seen with free T3 (P=0.218). The association between PDE8B and TSH was similar in 1981 (0.14 s.d./allele, 95% CI 0.04, 0.238) and 1994 (0.20 s.d./allele, 95% CI 0.102, 0.300) and even more consistent between PDE8B and free T4 in 1981 (−0.068 s.d./allele, 95% CI −0.167, 0.031) and 1994 (−0.07 s.d./allele, 95% CI −0.170, 0.030). No associations were seen between PDE8B and thyroid hormone parameters in individuals on l-T4. Conclusion Common genetic variation in PDE8B is associated with reciprocal changes in TSH and free T4 levels that are consistent over time and lost in individuals on l-T4. These findings identify a possible genetic marker reflecting variation in thyroid hormone output that will be of value in epidemiological studies and provides additional evidence that PDE8B is involved in TSH signaling in the thyroid. PMID:21317282

Population ecology of variegate darter (Etheostoma variatum) in Virginia

USGS Publications Warehouse

Argentina, Jane E.; Angermeier, Paul; Hallerman, Eric M.

2013-01-01

Variegate darters (Etheostoma variatum) were listed as endangered in Virginia in 1992. Reasons for listing included habitat degradation and concerns about current and future impacts of coal mining throughout their Virginia range. Prior to this research, little was known about variegate darter distribution, habitat use, or populations in Virginia. Two primary goals of this research were to gain knowledge about the current population ecology and the relationship between landscape-level factors (e.g., land cover changes, watershed size, isolation from other populations) on current and past variegate darter population sizes.We investigated distribution, habitat suitability, population genetics, and population size and structure of variegate darters in the upper Big Sandy River drainage, Buchanan, Dickenson, and Wise Co., Virginia. Our results indicate variegate darters are primarily found in the Levisa Fork, with highest densities and abundances between its confluence with Dismal Creek and the Virginia-Kentucky border. Sporadic occurrences in smaller tributaries to the Levisa and Tug forks indicate they exist more widely in low densities, especially near the confluence with the Tug and Levisa mainstems. Detection of variegate darters in smaller tributaries was inconsistent, with reach-level occupancy estimates varying among years. We detected young-of-year variegate darters every year we sampled, but age 1+ darters were indistinguishable from older darters based on standard length.Variegate darter population size and stability in Virginia were estimated via multiple methods, including site occupancy surveys, mark-recapture studies, and population genetic analysis. Using mark-recapture methods at five sites, we estimated overall population size in 2011 to be approximately 12,800 individuals in the 35-km reach between the Levisa Fork - Dismal Creek confluence and the Virginia-Kentucky border. Age structure seemed stable, with breeding adults and young-of-year collected annually during 2008-2011. Population genetic analysis indicated variegate darters in the Levisa Fork and its tributaries are part of a single genetic population. Historical and current genetic stability were seen in our analysis of the variegate darter population, with no genetic differentiation among riffles across the upper Levisa Fork watershed, indicating dispersal among these sites is enough to overcome random genetic drift. This population is genetically isolated from downstream populations by the dam at Fishtrap Lake, Pike Co., Kentucky, and is beginning to show genetic isolation from other nearby populations. As expected, the Virginia population is most closely related to those in the Russell Fork and Levisa Fork downstream of the dam.Regular monitoring of variegate darters in the Levisa Fork mainstem from the Dismal Creek confluence to the Virginia-Kentucky border would facilitate better understanding of normal fluctuations of population size and distribution, as well as assessments of population status. This reach encompasses the core of the variegate darter population in Virginia, and its persistence will determine long-term viability of this species. Given that little is known about long-term population trends, we suggest that annual site-occupancy and population size estimates be made at ten randomly selected riffles for at least ten years to understand normal levels of variability. Thereafter, these population parameters could be monitored bi-annually as a way to detect shrinking distribution or abundance, especially after any fish kill or other pollution event in the Levisa Fork. We further suggest that the sites upstream and downstream of the saline diffusor pipe be monitored to detect changes in the extent of the impact zone.Overall, the variegate darter population in Virginia appears stable, although primarily confined to the lower 35 km of the Levisa Fork. Nevertheless, variegate darters in Virginia remain susceptible to extirpation due to catastrophic events, both physical (chemical spill) and biological (disease outbreak or invasive species introduction).

Initial assessment of a model relating intratumoral genetic heterogeneity to radiological morphology

PubMed Central

Noterdaeme, O; Kelly, M; Friend, P; Soonowalla, Z; Steers, G; Brady, M

2010-01-01

Tumour heterogeneity has major implications for tumour development and response to therapy. Tumour heterogeneity results from mutations in the genes responsible for mismatch repair or maintenance of chromosomal stability. Cells with different genetic properties may grow at different rates and exhibit different resistance to therapeutic interventions. To date, there exists no approach to non-invasively assess tumour heterogeneity. Here we present a biologically inspired model of tumour growth, which relates intratumoral genetic heterogeneity to gross morphology visible on radiological images. The model represents the development of a tumour as a set of expanding spheres, each sphere representing a distinct clonal centre, with the sprouting of new spheres corresponding to new clonal centres. Each clonal centre may possess different characteristics relating to genetic composition, growth rate and response to treatment. We present a clinical example for which the model accurately tracks tumour growth and shows the correspondence to genetic variation (as determined by array comparative genomic hybridisation). One clinical implication of our work is that the assessment of heterogeneous tumours using Response Evaluation Criteria In Solid Tumours (RECIST) or volume measurements may not accurately reflect tumour growth, stability or the response to treatment. We believe that this is the first model linking the macro-scale appearance of tumours to their genetic composition. We anticipate that our model will provide a more informative way to assess the response of heterogeneous tumours to treatment, which is of increasing importance with the development of novel targeted anti-cancer treatments. PMID:19690073

Genetic constraints predict evolutionary divergence in Dalechampia blossoms.

PubMed

Bolstad, Geir H; Hansen, Thomas F; Pélabon, Christophe; Falahati-Anbaran, Mohsen; Pérez-Barrales, Rocío; Armbruster, W Scott

2014-08-19

If genetic constraints are important, then rates and direction of evolution should be related to trait evolvability. Here we use recently developed measures of evolvability to test the genetic constraint hypothesis with quantitative genetic data on floral morphology from the Neotropical vine Dalechampia scandens (Euphorbiaceae). These measures were compared against rates of evolution and patterns of divergence among 24 populations in two species in the D. scandens species complex. We found clear evidence for genetic constraints, particularly among traits that were tightly phenotypically integrated. This relationship between evolvability and evolutionary divergence is puzzling, because the estimated evolvabilities seem too large to constitute real constraints. We suggest that this paradox can be explained by a combination of weak stabilizing selection around moving adaptive optima and small realized evolvabilities relative to the observed additive genetic variance.

Genetic diversity and structure of an endangered desert shrub and the implications for conservation

Treesearch

Zhihao Su; Bryce A. Richardson; Li Zhuo; Xiaolong Jiang; Wenjun Li; Xiaoshan Kang

2017-01-01

Population genetic information can provide valuable insight for the conservation and management of threatened and endangered plant species. Tamarix taklamakanensis is an endangered shrub endemic to arid basins of northwestern China. This species serves to stabilize soils in this region, but has seen substantial loss in its abundance due to depletion of ground water....

Agrobacterium-mediated transformation in Alpinia galanga (Linn.) Willd. for enhanced acetoxychavicol acetate production.

PubMed

Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Mangamoori, Lakshmi Narasu; Giri, Archana

2012-09-01

Agrobacterium-mediated transformations ensure elevated amounts of secondary metabolite accumulation with genetic and biosynthetic stability. In the present study, Alpinia galanga rich in bioactive compounds was genetically transformed using different strains of Agrobacterium rhizogenes viz. LBA 9402, A(4), 532, 2364 and PRTGus. Even though a higher growth rate was obtained with the LBA 9402 strain, maximum acetoxychavicol acetate accumulation (ACA) was seen in the PRTGus transformant. PRTGus root line has shown 10.1 fold higher ACA content in comparison to the control roots. The lowest ACA production was shown by the A(4) transformant (4.9 fold). The quantification of ACA in the transformed roots was carried out by using HPLC, which was found to be in the order of PRTGus > LBA 9402 > 2364 > 532 > A(4). The fast growth rate of hairy roots, genetic stability and their ability to synthesize more than one metabolite offer a promising system for the production of valuable secondary metabolites.

A strong genetic correlation underlying a behavioural syndrome disappears during development because of genotype–age interactions

PubMed Central

Class, Barbara; Brommer, Jon E.

2015-01-01

In animal populations, as in humans, behavioural differences between individuals that are consistent over time and across contexts are considered to reflect personality, and suites of correlated behaviours expressed by individuals are known as behavioural syndromes. Lifelong stability of behavioural syndromes is often assumed, either implicitly or explicitly. Here, we use a quantitative genetic approach to study the developmental stability of a behavioural syndrome in a wild population of blue tits. We find that a behavioural syndrome formed by a strong genetic correlation of two personality traits in nestlings disappears in adults, and we demonstrate that genotype–age interaction is the likely mechanism underlying this change during development. A behavioural syndrome may hence change during organismal development, even when personality traits seem to be strongly physiologically or functionally linked in one age group. We outline how such developmental plasticity has important ramifications for understanding the mechanistic basis as well as the evolutionary consequences of behavioural syndromes. PMID:26041348

Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence

PubMed Central

Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

2015-01-01

The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445

Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence.

PubMed

Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

2015-05-06

The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.

Plant-parasite coevolution: bridging the gap between genetics and ecology.

PubMed

Brown, James K M; Tellier, Aurélien

2011-01-01

We review current ideas about coevolution of plants and parasites, particularly processes that generate genetic diversity. Frequencies of host resistance and parasite virulence alleles that interact in gene-for-gene (GFG) relationships coevolve in the familiar boom-and-bust cycle, in which resistance is selected when virulence is rare, and virulence is selected when resistance is common. The cycle can result in stable polymorphism when diverse ecological and epidemiological factors cause negative direct frequency-dependent selection (ndFDS) on host resistance, parasite virulence, or both, such that the benefit of a trait to fitness declines as its frequency increases. Polymorphism can also be stabilized by overdominance, when heterozygous hosts have greater resistance than homozygotes to diverse pathogens. Genetic diversity can also persist in the form of statistical polymorphism, sustained by random processes acting on gene frequencies and population size. Stable polymorphism allows alleles to be long-lived and genetic variation to be detectable in natural populations. In agriculture, many of the factors promoting stability in host-parasite interactions have been lost, leading to arms races of host defenses and parasite effectors. Copyright © 2011 by Annual Reviews. All rights reserved.

Development and analysis of a tick-borne encephalitis virus infectious clone using a novel and rapid strategy.

PubMed

Gritsun, T S; Gould, E A

1998-12-01

In less than 1 month we have constructed an infectious clone of attenuated tick-borne encephalitis virus (strain Vasilchenko) from 100 microl of unpurified virus suspension using long high fidelity PCR and a modified bacterial cloning system. Optimization of the 3' antisense primer concentration was essential to achieve PCR synthesis of an 11 kb cDNA copy of RNA from infectious virus. A novel system utilising two antisense primers, a 14-mer for reverse transcription and a 35-mer for long PCR, produced high yields of genomic length cDNA. Use of low copy number Able K cells and an incubation temperature of 28 degrees C increased the genetic stability of cloned cDNA. Clones containing 11 kb cDNA inserts produced colonies of reduced size, thus providing a positive selection system for full length clones. Sequencing of the infectious clone emphasised the improved fidelity of the method compared with conventional PCR and cloning methods. A simple and rapid strategy for genetic manipulation of the infectious clone is also described. These developments represent a significant advance in recombinant technology and should be applicable to positive stranded RNA viruses which cannot easily be purified or genetically manipulated.

Impact of genetic variation on three dimensional structure and function of proteins

PubMed Central

Bhattacharya, Roshni; Rose, Peter W.; Burley, Stephen K.

2017-01-01

The Protein Data Bank (PDB; http://wwpdb.org) was established in 1971 as the first open access digital data resource in biology with seven protein structures as its initial holdings. The global PDB archive now contains more than 126,000 experimentally determined atomic level three-dimensional (3D) structures of biological macromolecules (proteins, DNA, RNA), all of which are freely accessible via the Internet. Knowledge of the 3D structure of the gene product can help in understanding its function and role in disease. Of particular interest in the PDB archive are proteins for which 3D structures of genetic variant proteins have been determined, thus revealing atomic-level structural differences caused by the variation at the DNA level. Herein, we present a systematic and qualitative analysis of such cases. We observe a wide range of structural and functional changes caused by single amino acid differences, including changes in enzyme activity, aggregation propensity, structural stability, binding, and dissociation, some in the context of large assemblies. Structural comparison of wild type and mutated proteins, when both are available, provide insights into atomic-level structural differences caused by the genetic variation. PMID:28296894

Simultaneous selection for cowpea (Vigna unguiculata L.) genotypes with adaptability and yield stability using mixed models.

PubMed

Torres, F E; Teodoro, P E; Rodrigues, E V; Santos, A; Corrêa, A M; Ceccon, G

2016-04-29

The aim of this study was to select erect cowpea (Vigna unguiculata L.) genotypes simultaneously for high adaptability, stability, and yield grain in Mato Grosso do Sul, Brazil using mixed models. We conducted six trials of different cowpea genotypes in 2005 and 2006 in Aquidauana, Chapadão do Sul, Dourados, and Primavera do Leste. The experimental design was randomized complete blocks with four replications and 20 genotypes. Genetic parameters were estimated by restricted maximum likelihood/best linear unbiased prediction, and selection was based on the harmonic mean of the relative performance of genetic values method using three strategies: selection based on the predicted breeding value, having considered the performance mean of the genotypes in all environments (no interaction effect); the performance in each environment (with an interaction effect); and the simultaneous selection for grain yield, stability, and adaptability. The MNC99542F-5 and MNC99-537F-4 genotypes could be grown in various environments, as they exhibited high grain yield, adaptability, and stability. The average heritability of the genotypes was moderate to high and the selective accuracy was 82%, indicating an excellent potential for selection.

Increased yield stability of field-grown winter barley (Hordeum vulgare L.) varietal mixtures through ecological processes

PubMed Central

Creissen, Henry E.; Jorgensen, Tove H.; Brown, James K.M.

2016-01-01

Crop variety mixtures have the potential to increase yield stability in highly variable and unpredictable environments, yet knowledge of the specific mechanisms underlying enhanced yield stability has been limited. Ecological processes in genetically diverse crops were investigated by conducting field trials with winter barley varieties (Hordeum vulgare), grown as monocultures or as three-way mixtures in fungicide treated and untreated plots at three sites. Mixtures achieved yields comparable to the best performing monocultures whilst enhancing yield stability despite being subject to multiple predicted and unpredicted abiotic and biotic stresses including brown rust (Puccinia hordei) and lodging. There was compensation through competitive release because the most competitive variety overyielded in mixtures thereby compensating for less competitive varieties. Facilitation was also identified as an important ecological process within mixtures by reducing lodging. This study indicates that crop varietal mixtures have the capacity to stabilise productivity even when environmental conditions and stresses are not predicted in advance. Varietal mixtures provide a means of increasing crop genetic diversity without the need for extensive breeding efforts. They may confer enhanced resilience to environmental stresses and thus be a desirable component of future cropping systems for sustainable arable farming. PMID:27375312

Genetic stability of RSV-F expression and the restricted growth phenotype of a live attenuated PIV3 vectored RSV vaccine candidate (MEDI-534) following restrictive growth in human lung cells.

PubMed

Nelson, Christine L; Tang, Roderick S; Stillman, Elizabeth A

2013-08-12

MEDI-534 is the first live, attenuated and vectored respiratory syncytial virus (RSV) vaccine to be evaluated in seronegative children. It consists of a bovine/human parainfluenza virus type 3 (PIV3) backbone with the RSV fusion glycoprotein (RSV-F) expressed from the second position. The PIV3 fusion and hemaglutinin-neuraminidase proteins are human-derived. No small animal appropriately replicates the restrictive growth of bovine PIV3 (bPIV3) based viruses relative to human PIV3 (hPIV3) observed in the respiratory tract of rhesus monkeys and humans, making analysis of the genetic stability of the attenuation phenotype and maintenance of RSV-F expression difficult. Screening of multiple cell-lines identified MRC-5 cells as supporting permissive growth of hPIV3 while restricting bPIV3 and MEDI-534 growth. In MRC-5 cells, the peak titers of MEDI-534 were more than 20-fold lower compared to hPIV3 peak titers. After more than 10 multicycle passages in MRC-5 cells, genetic alterations were detected in MEDI-534 that contributed to a partial loss in restricted growth in MRC-5 cells and a decrease in RSV-F expression. These adaptive mutations did not occur in the RSV-F gene but were found in the polyA sequence upstream of the transgene. MRC-5 adapted MEDI-534 viruses (1) lost some attenuation but did not replicate to the level of hPIV3 in this cell line, (2) did not completely lose RSV-F expression and (3) were able to elicit a protective anti-RSV immune response in hamsters despite lower levels of RSV-F expression. Interestingly analysis of shed MEDI-534 from a recent clinical trial indicates that in some recipients similar mutations arise by day 7 or day 12 post immunization (in press) suggesting that these mutations can arise rapidly in the human host. The utility and limits of MRC-5 cells for characterizing the attenuation and RSV-F expression of MEDI-534 is discussed. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Towards XNA nanotechnology: new materials from synthetic genetic polymers

PubMed Central

Pinheiro, Vitor B.; Holliger, Philipp

2014-01-01

Nucleic acids display remarkable properties beyond information storage and propagation. The well-understood base pairing rules have enabled nucleic acids to be assembled into nanostructures of ever increasing complexity. Although nanostructures can be constructed using other building blocks, including peptides and lipids, it is the capacity to evolve that sets nucleic acids apart from all other nanoscale building materials. Nonetheless, the poor chemical and biological stability of DNA and RNA constrain their applications. Recent advances in nucleic acid chemistry and polymerase engineering enable the synthesis, replication, and evolution of a range of synthetic genetic polymers (XNAs) with improved chemical and biological stability. We discuss the impact of this technology on the generation of XNA ligands, enzymes, and nanostructures with tailor-made chemistry. PMID:24745974

The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing.

PubMed Central

Sanchez, A; Trappier, S G; Mahy, B W; Peters, C J; Nichol, S T

1996-01-01

In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein (130 kDa) is encoded in two reading frames, which are linked by transcriptional editing. This editing results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller (50-70 kDa), nonstructural, secreted glycoprotein, which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new (fourth) subtype of EBO virus. In contrast, the EBO virus isolate from the 1995 outbreak in Kikwit, Zaire, is virtually identical to the virus that caused a similar epidemic in Yambuku, Zaire, almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild. Images Fig. 2 Fig. 3 PMID:8622982

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

PubMed

Machiela, Mitchell J; Hofmann, Jonathan N; Carreras-Torres, Robert; Brown, Kevin M; Johansson, Mattias; Wang, Zhaoming; Foll, Matthieu; Li, Peng; Rothman, Nathaniel; Savage, Sharon A; Gaborieau, Valerie; McKay, James D; Ye, Yuanqing; Henrion, Marc; Bruinsma, Fiona; Jordan, Susan; Severi, Gianluca; Hveem, Kristian; Vatten, Lars J; Fletcher, Tony; Koppova, Kvetoslava; Larsson, Susanna C; Wolk, Alicja; Banks, Rosamonde E; Selby, Peter J; Easton, Douglas F; Pharoah, Paul; Andreotti, Gabriella; Freeman, Laura E Beane; Koutros, Stella; Albanes, Demetrius; Mannisto, Satu; Weinstein, Stephanie; Clark, Peter E; Edwards, Todd E; Lipworth, Loren; Gapstur, Susan M; Stevens, Victoria L; Carol, Hallie; Freedman, Matthew L; Pomerantz, Mark M; Cho, Eunyoung; Kraft, Peter; Preston, Mark A; Wilson, Kathryn M; Gaziano, J Michael; Sesso, Howard S; Black, Amanda; Freedman, Neal D; Huang, Wen-Yi; Anema, John G; Kahnoski, Richard J; Lane, Brian R; Noyes, Sabrina L; Petillo, David; Colli, Leandro M; Sampson, Joshua N; Besse, Celine; Blanche, Helene; Boland, Anne; Burdette, Laurie; Prokhortchouk, Egor; Skryabin, Konstantin G; Yeager, Meredith; Mijuskovic, Mirjana; Ognjanovic, Miodrag; Foretova, Lenka; Holcatova, Ivana; Janout, Vladimir; Mates, Dana; Mukeriya, Anush; Rascu, Stefan; Zaridze, David; Bencko, Vladimir; Cybulski, Cezary; Fabianova, Eleonora; Jinga, Viorel; Lissowska, Jolanta; Lubinski, Jan; Navratilova, Marie; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Benhamou, Simone; Cancel-Tassin, Geraldine; Cussenot, Olivier; Bueno-de-Mesquita, H Bas; Canzian, Federico; Duell, Eric J; Ljungberg, Börje; Sitaram, Raviprakash T; Peters, Ulrike; White, Emily; Anderson, Garnet L; Johnson, Lisa; Luo, Juhua; Buring, Julie; Lee, I-Min; Chow, Wong-Ho; Moore, Lee E; Wood, Christopher; Eisen, Timothy; Larkin, James; Choueiri, Toni K; Lathrop, G Mark; Teh, Bin Tean; Deleuze, Jean-Francois; Wu, Xifeng; Houlston, Richard S; Brennan, Paul; Chanock, Stephen J; Scelo, Ghislaine; Purdue, Mark P

2017-11-01

Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R 2 >0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma. Published by Elsevier B.V.

Genetic Polymorphisms in RNA Binding Proteins Contribute to Breast Cancer Survival

PubMed Central

Upadhyay, Rohit; Sanduja, Sandhya; Kaza, Vimala; Dixon, Dan A.

2012-01-01

The RNA-binding proteins TTP and HuR control expression of numerous genes associated with breast cancer pathogenesis by regulating mRNA stability. However, the role of genetic variation in TTP (ZFP36) and HuR (ELAVL1) genes is unknown in breast cancer prognosis. A total of 251 breast cancer patients (170 Caucasians and 81 African-Americans) were enrolled and followed-up from 2001 to 2011 (or until death). Genotyping was performed for 10 SNPs in ZFP36 and 7 in ELAVL1 genes. On comparing both races with one another, significant differences were found for clinical and genetic variables. The influence of genetic polymorphisms on survival was analyzed by using Cox-regression, Kaplan-Meier analysis, and the log-rank test. Univariate (Kaplan-Meier/Cox-regression) and multivariate (Cox-regression) analysis showed that the TTP gene polymorphism ZFP36*2 A>G was significantly associated with poor prognosis of Caucasian patients (HR = 2.03; 95% CI = 1.09–3.76; P = 0.025; log-rank P = 0.022). None of the haplotypes, but presence of more than six risk genotypes in Caucasian patients, was significantly associated with poor prognosis (HR=2.42; 95% CI=1.17–4.99; P = 0.017; log-rank P = 0.007). The effect of ZFP36*2 A>G on gene expression was evaluated from patients' tissue samples. Both TTP mRNA and protein expression was significantly decreased in ZFP36*2 G allele carriers compared to A allele homozygotes. Conversely, upregulation of the TTP-target gene COX-2 was observed ZFP36*2 G allele carriers. Through its ability to attenuate TTP gene expression, the ZFP36*2 A>G gene polymorphism has appeared as a novel prognostic breast cancer marker in Caucasian patients. PMID:22907529

Genetic variants affecting telomere length are associated with the prognosis of esophageal squamous cell carcinoma in a Chinese population.

PubMed

Lu, Yue; Yan, Caiwang; Du, Jiangbo; Ji, Yong; Gao, Yong; Zhu, Xun; Yu, Fei; Huang, Tongtong; Dai, Juncheng; Ma, Hongxia; Jiang, Yue; Chen, Jiaping; Shen, Hongbing; Jin, Guangfu; Yin, Yongmei; Hu, Zhibin

2017-03-01

Telomeres are essential for maintaining chromosomal stability and are crucial in tumor progression. Previous studies have explored the associations between telomere length and cancer prognosis, but the findings are inconclusive. Genome-wide association studies have identified several genetic variants associated with telomere length in Caucasians. However, the roles of telomere length and related genetic variants on esophageal squamous cell carcinoma (ESCC) prognosis are largely unknown. Therefore, we conducted a case-cohort study with 431 ESCC patients to assess the associations between relative telomere length (RTL), eight known telomere length related variants and the overall survival of ESCC in Chinese population. We found that as compared with the reference group, patients in the fifth (the longest) quintile had a significantly better prognosis [(adjusted hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34-0.98, P = 0.041]. Furthermore, A allele of rs2736108 was significantly associated with both the increased RTL (P = 0.048) and the better prognosis of ESCC (adjusted HR = 0.55, 95%CI = 0.38-0.79, P = 1.31 × 10 -3 ). Mediation analysis indicated that the effect of rs2736108 on ESCC prognosis was partly explained by RTL (1.99%). Stepwise Cox proportional hazard analysis suggested that rs2736108 played an important protective role in ESCC prognosis (HR = 0.57, 95%CI = 0.40-0.81, P = 1.97 × 10 - 3 ). Our findings provide evidence that prolonged telomere length is a protective factor for ESCC patients' survival and the known telomere length related genetic variant rs2736108 can contribute to the prognosis of ESCC as well in Chinese population. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Assessment of reference genes for reliable analysis of gene transcription by RT-qPCR in ovine leukocytes.

PubMed

Mahakapuge, T A N; Scheerlinck, J-P Y; Rojas, C A Alvarez; Every, A L; Hagen, J

2016-03-01

With the availability of genetic sequencing data, quantitative reverse transcription PCR (RT-qPCR) is increasingly being used for the quantification of gene transcription across species. Too often there is little regard to the selection of reference genes and the impact that a poor choice has on data interpretation. Indeed, RT-qPCR provides a snapshot of relative gene transcription at a given time-point, and hence is highly dependent on the stability of the transcription of the reference gene(s). Using ovine efferent lymph cells and peripheral blood mono-nuclear cells (PBMCs), the two most frequently used leukocytes in immunological studies, we have compared the stability of transcription of the most commonly used ovine reference genes: YWHAZ, RPL-13A, PGK1, B2M, GAPDH, HPRT, SDHA and ACTB. Using established algorithms for reference gene normalization "geNorm" and "Norm Finder", PGK1, GAPDH and YWHAZ were deemed the most stably transcribed genes for efferent leukocytes and PGK1, YWHAZ and SDHA were optimal in PBMCs. These genes should therefore be considered for accurate and reproducible RT-qPCR data analysis of gene transcription in sheep. Copyright © 2016. Published by Elsevier B.V.

Continuous and discontinuous phase transitions in the evolution of a polygenic trait under stabilizing selective pressure

NASA Astrophysics Data System (ADS)

Fierro, Annalisa; Cocozza, Sergio; Monticelli, Antonella; Scala, Giovanni; Miele, Gennaro

2017-06-01

The presence of phenomena analogous to phase transition in Statistical Mechanics has been suggested in the evolution of a polygenic trait under stabilizing selection, mutation and genetic drift. By using numerical simulations of a model system, we analyze the evolution of a population of N diploid hermaphrodites in random mating regime. The population evolves under the effect of drift, selective pressure in form of viability on an additive polygenic trait, and mutation. The analysis allows to determine a phase diagram in the plane of mutation rate and strength of selection. The involved pattern of phase transitions is characterized by a line of critical points for weak selective pressure (smaller than a threshold), whereas discontinuous phase transitions, characterized by metastable hysteresis, are observed for strong selective pressure. A finite-size scaling analysis suggests the analogy between our system and the mean-field Ising model for selective pressure approaching the threshold from weaker values. In this framework, the mutation rate, which allows the system to explore the accessible microscopic states, is the parameter controlling the transition from large heterozygosity ( disordered phase) to small heterozygosity ( ordered one).

Species interactions differ in their genetic robustness

DOE PAGES

Chubiz, Lon M.; Granger, Brian R.; Segre, Daniel; ...

2015-04-14

Conflict and cooperation between bacterial species drive the composition and function of microbial communities. Stability of these emergent properties will be influenced by the degree to which species' interactions are robust to genetic perturbations. We use genome-scale metabolic modeling to computationally analyze the impact of genetic changes when Escherichia coli and Salmonella enterica compete, or cooperate. We systematically knocked out in silico each reaction in the metabolic network of E. coli to construct all 2583 mutant stoichiometric models. Then, using a recently developed multi-scale computational framework, we simulated the growth of each mutant E. coli in the presence of S.more » enterica. The type of interaction between species was set by modulating the initial metabolites present in the environment. We found that the community was most robust to genetic perturbations when the organisms were cooperating. Species ratios were more stable in the cooperative community, and community biomass had equal variance in the two contexts. Additionally, the number of mutations that have a substantial effect is lower when the species cooperate than when they are competing. In contrast, when mutations were added to the S. enterica network the system was more robust when the bacteria were competing. These results highlight the utility of connecting metabolic mechanisms and studies of ecological stability. Cooperation and conflict alter the connection between genetic changes and properties that emerge at higher levels of biological organization.« less

A case of isolation by distance and short-term temporal stability of population structure in brown trout (Salmo trutta) within the River Dart, southwest England

PubMed Central

Griffiths, Andrew M; Koizumi, Itsuro; Bright, Dylan; Stevens, Jamie R

2009-01-01

Salmonid fishes exhibit high levels of population differentiation. In particular, the brown trout (Salmo trutta L.) demonstrates complex within river drainage genetic structure. Increasingly, these patterns can be related to the underlying evolutionary models, of which three scenarios (member-vagrant hypothesis, metapopulation model and panmixia) facilitate testable predictions for investigations into population structure. We analysed 1225 trout collected from the River Dart, a 75 km long river located in southwest England. Specimens were collected from 22 sample sites across three consecutive summers (2001–2003) and genetic variation was examined at nine microsatellite loci. A hierarchical analysis of molecular variance revealed that negligible genetic variation was attributed among temporal samples. The highest levels of differentiation occurred among samples isolated above barriers to fish movement, and once these samples were removed, a significant effect of isolation-by-distance was observed. These results suggest that, at least in the short-term, ecological events are more important in shaping the population structure of Dart trout than stochastic extinction events, and certainly do not contradict the expectations of a member-vagrant hypothesis. Furthermore, individual-level spatial autocorrelation analyses support previous recommendations for the preservation of a number of spawning sites spaced throughout the tributary system to conserve the high levels of genetic variation identified in salmonid species. PMID:25567897

Gαs Relays Sphingosine-1-Phosphate Receptor 1 Signaling to Stabilize Vascular Endothelial-Cadherin at Endothelial Junctions to Control Mouse Embryonic Vascular Integrity.

PubMed

Shao, Ximing; Liu, Ke; Fan, Yi; Ding, Zhihao; Chen, Min; Zhu, Minyan; Weinstein, Lee S; Li, Hongchang; Li, Huashun

2015-11-20

Sphingosine-1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor (GPCR), controls vascular stability by stabilizing vascular endothelial (VE)-cadherin junctional localization and inhibiting vascular endothelial growth factor receptor 2 (VEGFR2) signaling. However, the molecular mechanisms that link S1PR1 signaling to intracellular effectors remain unknown. In this study, we demonstrate that the heterotrimeric G protein subfamily member Gαs, encoded by GNAS, acts as a relay mediator of S1PR1 signaling to control vascular integrity by stabilizing VE-cadherin at endothelial junctions. The endothelial cell-specific deletion of Gαs in mice causes early embryonic lethality with massive hemorrhage and a disorganized vasculature. The immunostaining results revealed that Gαs deletion remarkably reduces the junctional localization of VE-cadherin, whereas the mural cell coverage of the vessels is not impaired. In addition, we found that Gαs depletion blocks the S1PR1-activation induced VE-cadherin stabilization at junctions, supporting that Gαs acts downstream of S1PR1 signaling. Thus, our results demonstrate that Gαs is an essential mediator to relay S1PR1 signaling and maintain vascular integrity. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Differentiation of five body fluids from forensic samples by expression analysis of four microRNAs using quantitative PCR.

PubMed

Sauer, Eva; Reinke, Ann-Kathrin; Courts, Cornelius

2016-05-01

Applying molecular genetic approaches for the identification of forensically relevant body fluids, which often yield crucial information for the reconstruction of a potential crime, is a current topic of forensic research. Due to their body fluid specific expression patterns and stability against degradation, microRNAs (miRNA) emerged as a promising molecular species, with a range of candidate markers published. The analysis of miRNA via quantitative Real-Time PCR, however, should be based on a relevant strategy of normalization of non-biological variances to deliver reliable and biologically meaningful results. The herein presented work is the as yet most comprehensive study of forensic body fluid identification via miRNA expression analysis based on a thoroughly validated qPCR procedure and unbiased statistical decision making to identify single source samples. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells

PubMed Central

Carlile, Thomas M.; Rojas-Duran, Maria F.; Zinshteyn, Boris; Shin, Hakyung; Bartoli, Kristen M.; Gilbert, Wendy V.

2014-01-01

Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs1, enhances the function of transfer RNA and ribosomal RNA by stabilizing RNA structure2–8. mRNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function – it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding center9,10. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological was unclear. Here we present a comprehensive analysis of pseudouridylation in yeast and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as 100 novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease11–13. PMID:25192136

Establishment of an efficient transformation system for Pleurotus ostreatus.

PubMed

Lei, Min; Wu, Xiangli; Zhang, Jinxia; Wang, Hexiang; Huang, Chenyang

2017-11-21

Pleurotus ostreatus is widely cultivated worldwide, but the lack of an efficient transformation system regarding its use restricts its genetic research. The present study developed an improved and efficient Agrobacterium tumefaciens-mediated transformation method in P. ostreatus. Four parameters were optimized to obtain the most efficient transformation method. The strain LBA4404 was the most suitable for the transformation of P. ostreatus. A bacteria-to-protoplast ratio of 100:1, an acetosyringone (AS) concentration of 0.1 mM, and 18 h of co-culture showed the best transformation efficiency. The hygromycin B phosphotransferase gene (HPH) was used as the selective marker, and EGFP was used as the reporter gene in this study. Southern blot analysis combined with EGFP fluorescence assay showed positive results, and mitotic stability assay showed that more than 75% transformants were stable after five generations. These results showed that our transformation method is effective and stable and may facilitate future genetic studies in P. ostreatus.

Highly-efficient liposome-mediated transformation system for the basidiomycetous fungus Flammulina velutipes.

PubMed

Shi, Liang; Chen, Dongdong; Xu, Chao; Ren, Ang; Yu, Hanshou; Zhao, Mingwen

2017-07-11

Flammulina velutipes is a well-known edible mushroom cultivated all over the world. However, because of the low transformation frequency, the expensive instruments required, and the complicated, time-consuming procedures necessary, there is insufficient genetic research on F. velutipes. In this study, we report a liposome-mediated transformation (LMT) system for the genetic transformation of F. velutipes. Using the LMT system, we obtained 82 ± 4 stable F. velutipes transformants per 10 5 protoplasts, which is a clear increase in transformation frequency compared to the other methods used. We were able to detect the expression of an EGFP reporter gene in the F. velutipes transformants using fluorescence imaging assays. Furthermore, we used this method to transfer the laccase gene into F. velutipes and found that the transcriptional level and enzymatic activity increased in these transformants. Mitotic stability analysis showed that all of the selected transformants remained mitotically stable, even after five successive rounds of sub-culturing. These results demonstrate a new transgenic approach that will facilitate F. velutipes research.

Identification of Natural RORγ Ligands that Regulate the Development of Lymphoid Cells

PubMed Central

Santori, Fabio R.; Huang, Pengxiang; van de Pavert, Serge A.; Douglass, Eugene F.; Leaver, David J.; Haubrich, Brad A.; Keber, Rok; Lorbek, Gregor; Konijn, Tanja; Rosales, Brittany N.; Horvat, Simon; Rozman, Damjana; Rahier, Alain; Mebius, Reina E.; Rastinejad, Fraydoon; Nes, W. David; Littman, Dan R.

2015-01-01

SUMMARY Mice deficient in the nuclear hormone receptor RORγt have defective development of thymocytes, lymphoid organs, Th17 cells and type 3 innate lymphoid cells. RORγt binds to oxysterols derived from cholesterol catabolism but it is not clear whether these are its natural ligands. Here, we show that sterol lipids are necessary and sufficient to drive RORγt-dependent transcription. We combined overexpression, RNA interference and genetic deletion of metabolic enzymes to study RORγ-dependent transcription. Our results are consistent with the RORγt ligand(s) being a cholesterol biosynthetic intermediate (CBI) downstream of lanosterol and upstream of zymosterol. Analysis of lipids bound to RORγ identified molecules with molecular weights consistent with CBIs. Furthermore, CBIs stabilized the RORγ ligand-binding domain and induced co-activator recruitment. Genetic deletion of metabolic enzymes upstream of the RORγt-ligand(s) affected the development of lymph nodes and Th17 cells. Our data suggest that CBIs play a role in lymphocyte development potentially through regulation of RORγt. PMID:25651181

Wilhelm Weinberg’s Early Contribution to Segregation Analysis

PubMed Central

Stark, Alan; Seneta, Eugene

2013-01-01

Wilhelm Weinberg (1862–1937) is a largely forgotten pioneer of human and medical genetics. His name is linked with that of the English mathematician G. H. Hardy in the Hardy–Weinberg law, pervasive in textbooks on population genetics since it expresses stability over generations of zygote frequencies AA, Aa, aa under random mating. One of Weinberg’s signal contributions, in an article whose centenary we celebrate, was to verify that Mendel’s segregation law still held in the setting of human heredity, contrary to the then-prevailing view of William Bateson (1861–1926), the leading Mendelian geneticist of the time. Specifically, Weinberg verified that the proportion of recessive offspring genotypes aa in human parental crossings Aa × Aa (that is, the segregation ratio for such a setting) was indeed p=14. We focus in a nontechnical way on his procedure, called the simple sib method, and on the heated controversy with Felix Bernstein (1878–1956) in the 1920s and 1930s over work stimulated by Weinberg’s article. PMID:24018765

Masseter function and skeletal malocclusion.

PubMed

Sciote, J J; Raoul, G; Ferri, J; Close, J; Horton, M J; Rowlerson, A

2013-04-01

The aim of this work is to review the relationship between the function of the masseter muscle and the occurrence of malocclusions. An analysis was made of the masseter muscle samples from subjects who underwent mandibular osteotomies. The size and proportion of type-II fibers (fast) decreases as facial height increases. Patients with mandibular asymmetry have more type-II fibers on the side of their deviation. The insulin-like growth factor and myostatin are expressed differently depending on the sex and fiber diameter. These differences in the distribution of fiber types and gene expression of this growth factor may be involved in long-term postoperative stability and require additional investigations. Muscle strength and bone length are two genetically determined factors in facial growth. Myosin 1H (MYOH1) is associated with prognathia in Caucasians. As future objectives, we propose to characterize genetic variations using "Genome Wide Association Studies" data and their relationships with malocclusions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

BacMam Virus Transduced Cardiomyoblasts Can Be Used for Myocardial Transplantation Using AP-PEG-A Microcapsules: Molecular Cloning, Preparation, and In Vitro Analysis

PubMed Central

Paul, Arghya; Khan, Afshan Afsar; Shum-Tim, Dominique; Prakash, Satya

2010-01-01

The potential of genetically modified cardiomyoblasts in treating damaged myocardium is well known. However, efficient delivery of these cells is of major concern during treatment. The limiting factors are the massive cell death that occurs soon after their intramyocardial transplantation into the beating heart. To address these problems, we generated recombinant baculoviruses (BacMam viruses) which efficiently transduced cardiomyoblast cells under optimized conditions. These genetically modified cells were then protected in a new polymeric microcapsule using poly-ethylene-glycol (PEG), alginate, and poly-L-lysine (PLL) polymers for efficient delivery. Results showed that microcapsules maintain cell viability and support cell proliferation for at least 30 days. The capsules exhibit strong immunoprotective potential and have high mechanical and osmotic stability with more than 70% intact capsules. The encased transduced cells showed a rapid transgene expression inside the capsule for at least 15 days. However, preclinical studies are needed to further explore its long-term functional benefits. PMID:21331169

BacMam virus transduced cardiomyoblasts can be used for myocardial transplantation using AP-PEG-A microcapsules: molecular cloning, preparation, and in vitro analysis.

PubMed

Paul, Arghya; Khan, Afshan Afsar; Shum-Tim, Dominique; Prakash, Satya

2010-01-01

The potential of genetically modified cardiomyoblasts in treating damaged myocardium is well known. However, efficient delivery of these cells is of major concern during treatment. The limiting factors are the massive cell death that occurs soon after their intramyocardial transplantation into the beating heart. To address these problems, we generated recombinant baculoviruses (BacMam viruses) which efficiently transduced cardiomyoblast cells under optimized conditions. These genetically modified cells were then protected in a new polymeric microcapsule using poly-ethylene-glycol (PEG), alginate, and poly-L-lysine (PLL) polymers for efficient delivery. Results showed that microcapsules maintain cell viability and support cell proliferation for at least 30 days. The capsules exhibit strong immunoprotective potential and have high mechanical and osmotic stability with more than 70% intact capsules. The encased transduced cells showed a rapid transgene expression inside the capsule for at least 15 days. However, preclinical studies are needed to further explore its long-term functional benefits.

A population genetic interpretation of GWAS findings for human quantitative traits

PubMed Central

Bullaughey, Kevin; Hudson, Richard R.; Sella, Guy

2018-01-01

Human genome-wide association studies (GWASs) are revealing the genetic architecture of anthropomorphic and biomedical traits, i.e., the frequencies and effect sizes of variants that contribute to heritable variation in a trait. To interpret these findings, we need to understand how genetic architecture is shaped by basic population genetics processes—notably, by mutation, natural selection, and genetic drift. Because many quantitative traits are subject to stabilizing selection and because genetic variation that affects one trait often affects many others, we model the genetic architecture of a focal trait that arises under stabilizing selection in a multidimensional trait space. We solve the model for the phenotypic distribution and allelic dynamics at steady state and derive robust, closed-form solutions for summary statistics of the genetic architecture. Our results provide a simple interpretation for missing heritability and why it varies among traits. They predict that the distribution of variances contributed by loci identified in GWASs is well approximated by a simple functional form that depends on a single parameter: the expected contribution to genetic variance of a strongly selected site affecting the trait. We test this prediction against the results of GWASs for height and body mass index (BMI) and find that it fits the data well, allowing us to make inferences about the degree of pleiotropy and mutational target size for these traits. Our findings help to explain why the GWAS for height explains more of the heritable variance than the similarly sized GWAS for BMI and to predict the increase in explained heritability with study sample size. Considering the demographic history of European populations, in which these GWASs were performed, we further find that most of the associations they identified likely involve mutations that arose shortly before or during the Out-of-Africa bottleneck at sites with selection coefficients around s = 10−3. PMID:29547617

Genetic constraints predict evolutionary divergence in Dalechampia blossoms

PubMed Central

Bolstad, Geir H.; Hansen, Thomas F.; Pélabon, Christophe; Falahati-Anbaran, Mohsen; Pérez-Barrales, Rocío; Armbruster, W. Scott

2014-01-01

If genetic constraints are important, then rates and direction of evolution should be related to trait evolvability. Here we use recently developed measures of evolvability to test the genetic constraint hypothesis with quantitative genetic data on floral morphology from the Neotropical vine Dalechampia scandens (Euphorbiaceae). These measures were compared against rates of evolution and patterns of divergence among 24 populations in two species in the D. scandens species complex. We found clear evidence for genetic constraints, particularly among traits that were tightly phenotypically integrated. This relationship between evolvability and evolutionary divergence is puzzling, because the estimated evolvabilities seem too large to constitute real constraints. We suggest that this paradox can be explained by a combination of weak stabilizing selection around moving adaptive optima and small realized evolvabilities relative to the observed additive genetic variance. PMID:25002700

Floral trait variation and integration as a function of sexual deception in Gorteria diffusa

PubMed Central

Ellis, Allan G.; Brockington, Samuel F.; de Jager, Marinus L.; Mellers, Gregory; Walker, Rachel H.; Glover, Beverley J.

2014-01-01

Phenotypic integration, the coordinated covariance of suites of morphological traits, is critical for proper functioning of organisms. Angiosperm flowers are complex structures comprising suites of traits that function together to achieve effective pollen transfer. Floral integration could reflect shared genetic and developmental control of these traits, or could arise through pollinator-imposed stabilizing correlational selection on traits. We sought to expose mechanisms underlying floral trait integration in the sexually deceptive daisy, Gorteria diffusa, by testing the hypothesis that stabilizing selection imposed by male pollinators on floral traits involved in mimicry has resulted in tighter integration. To do this, we quantified patterns of floral trait variance and covariance in morphologically divergent G. diffusa floral forms representing a continuum in the levels of sexual deception. We show that integration of traits functioning in visual attraction of male pollinators increases with pollinator deception, and is stronger than integration of non-mimicry trait modules. Consistent patterns of within-population trait variance and covariance across floral forms suggest that integration has not been built by stabilizing correlational selection on genetically independent traits. Instead pollinator specialization has selected for tightened integration within modules of linked traits. Despite potentially strong constraint on morphological evolution imposed by developmental genetic linkages between traits, we demonstrate substantial divergence in traits across G. diffusa floral forms and show that divergence has often occurred without altering within-population patterns of trait correlations. PMID:25002705

Saccharomyces cerevisiae × Saccharomyces uvarum hybrids generated under different conditions share similar winemaking features.

PubMed

Origone, Andrea Cecilia; Rodríguez, María Eugenia; Oteiza, Juan Martín; Querol, Amparo; Lopes, Christian Ariel

2018-01-01

Interspecific hybrids among species in the Saccharomyces genus are frequently detected in anthropic habitats and can also be obtained easily in the laboratory. This occurs because the most important genetic barriers among Saccharomyces species are post-zygotic. Depending on several factors, including the involved strains, the hybridization mechanism and stabilization conditions, hybrids that bear differential genomic constitutions, and hence phenotypic variability, can be obtained. In the present study, Saccharomyces cerevisiae × Saccharomyces uvarum hybrids were constructed using genetically and physiologically different S. uvarum parents at distinct temperatures (13 and 20°C). The effect of those variables on the main oenological features of the wines obtained with these hybrids was evaluated. Hybrids were successfully obtained in all cases. However, genetic stabilization based on successive fermentations in white wine at 13°C was significantly longer than that at 20°C. Our results demonstrated that, irrespective of the S. uvarum parent and temperature used for hybrid generation and stabilization, similar physicochemical and aromatic features were found in wines. The hybrids generated herein were characterized by low ethanol production, high glycerol synthesis and the capacity to grow at low temperature and to produce malic acid with particular aroma profiles. These features make these hybrids useful for the new winemaking industry within the climate change era frame. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

A Recombinant Saccharomyces cerevisiae Strain Overproducing Mannoproteins Stabilizes Wine against Protein Haze▿

PubMed Central

Gonzalez-Ramos, Daniel; Cebollero, Eduardo; Gonzalez, Ramon

2008-01-01

Stabilization against protein haze was one of the first positive properties attributed to yeast mannoproteins in winemaking. In previous work we demonstrated that deletion of KNR4 leads to increased mannoprotein release in laboratory Saccharomyces cerevisiae strains. We have now constructed strains with KNR4 deleted in two different industrial wine yeast backgrounds. This required replacement of two and three alleles of KNR4 for the EC1118 and T73-4 backgrounds, respectively, and the use of three different selection markers for yeast genetic transformation. The actual effect of the genetic modification was dependent on both the genetic background and the culture conditions. The fermentation performance of T73-4 derivatives was clearly impaired, and these derivatives did not contribute to the protein stability of the wine, even though they showed increased mannoprotein release in vitro. In contrast, the EC1118 derivative with both alleles of KNR4 deleted released increased amounts of mannoproteins both in vitro and during wine fermentation assays, and the resulting wines were consistently less susceptible to protein haze. The fermentation performance of this strain was slightly impaired, but only with must with a very high sugar content. These results pave the way for the development of new commercial strains with the potential to improve several mannoprotein-related quality and technological parameters of wine. PMID:18606802

Genetic and environmental integration of the hawkmoth pollination syndrome in Ruellia humilis (Acanthaceae).

PubMed

Heywood, John S; Michalski, Joseph S; McCann, Braden K; Russo, Amber D; Andres, Kara J; Hall, Allison R; Middleton, Tessa C

2017-05-01

The serial homology of floral structures has made it difficult to assess the relative contributions of selection and constraint to floral integration. The interpretation of floral integration may also be clouded by the tacit, but largely untested, assumption that genetic and environmental perturbations affect trait correlations in similar ways. In this study, estimates of both the genetic and environmental correlations between components of the hawkmoth pollination syndrome are presented for chasmogamous flowers of Ruellia humilis , including two levels of control for serial homology. A greenhouse population for quantitative genetic analysis was generated by a partial diallel cross between field-collected plants. An average of 634 chasmogamous flowers were measured for each of eight floral traits that contribute to the hawkmoth syndrome. Genetic correlations (across parents) and environmental correlations (across replicate flowers) were estimated by restricted maximum likelihood. Stigma height, anther height and floral tube length were very tightly integrated in their responses to both genetic and environmental perturbations. The inclusion of floral disc width as a control for serial homology suggests this integration is an adaptive response to correlational selection imposed by pollinators. In contrast, integration of non-homologous traits was low. Furthermore, when comparisons between the dimensions of serially homologous structures were excluded, the genetic and environmental correlation matrices showed little congruence. The results suggest that hawkmoths have imposed strong correlational selection on floral traits involved in the deposition and removal of pollen, and that this is a consequence of stabilizing selection on the relative positions of stigmas and anthers in the face of substantial flower size variation. Low integration of other floral traits, and conflicting patterns of genetic and environmental correlations among these traits, suggest weak or no correlational selection within the range of variability expressed within a population. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Mapping genetic variations to three-dimensional protein structures to enhance variant interpretation: a proposed framework.

PubMed

Glusman, Gustavo; Rose, Peter W; Prlić, Andreas; Dougherty, Jennifer; Duarte, José M; Hoffman, Andrew S; Barton, Geoffrey J; Bendixen, Emøke; Bergquist, Timothy; Bock, Christian; Brunk, Elizabeth; Buljan, Marija; Burley, Stephen K; Cai, Binghuang; Carter, Hannah; Gao, JianJiong; Godzik, Adam; Heuer, Michael; Hicks, Michael; Hrabe, Thomas; Karchin, Rachel; Leman, Julia Koehler; Lane, Lydie; Masica, David L; Mooney, Sean D; Moult, John; Omenn, Gilbert S; Pearl, Frances; Pejaver, Vikas; Reynolds, Sheila M; Rokem, Ariel; Schwede, Torsten; Song, Sicheng; Tilgner, Hagen; Valasatava, Yana; Zhang, Yang; Deutsch, Eric W

2017-12-18

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods.

Evolutionary speed of species invasions.

PubMed

García-Ramos, Gisela; Rodríguez, Diego

2002-04-01

Successful invasion may depend of the capacity of a species to adjust genetically to a spatially varying environment. This research modeled a species invasion by examining the interaction between a quantitative genetic trait and population density. It assumed: (I) a quantitative genetic trait describes the adaptation of an individual to its local ecological conditions; (2) populations far from the local optimum grow more slowly than those near the optimum; and (3) the evolution of a trait depends on local population density, because differences in local population densities cause asymmetrical gene flow. This genetics-density interaction determined the propagation speed of populations. Numerical simulations showed that populations spread by advancing as two synchronic traveling waves, one for population density and one for trait adaptation. The form of the density wave was a step front that advances homogenizing populations at their carrying capacity; the adaptation wave was a curve with finite slope that homogenizes populations at full adaptation. The largest speed of population expansion, for a dimensionless analysis, corresponded to an almost homogeneous spatial environment when this model approached an ecological description such as the Fisher-Skellam's model. A large genetic response also favored faster speeds. Evolutionary speeds, in a natural scale, showed a wide range of rates that were also slower compared to models that only consider demographics. This evolutionary speed increased with high heritability, strong stabilizing selection, and high intrinsic growth rate. It decreased for steeper environmental gradients. Also indicated was an optimal dispersal rate over which evolutionary speed declined. This is expected because dispersal moves individuals further, but homogenizes populations genetically, making them maladapted. The evolutionary speed was compared to observed data. Furthermore, a moderate increase in the speed of expansion was predicted for ecological changes related to global warming.

Stability Performance of Inductively Coupled Plasma Mass Spectrometry-Phenotyped Kernel Minerals Concentration and Grain Yield in Maize in Different Agro-Climatic Zones

PubMed Central

Mallikarjuna, Mallana Gowdra; Thirunavukkarasu, Nepolean; Hossain, Firoz; Bhat, Jayant S.; Jha, Shailendra K.; Rathore, Abhishek; Agrawal, Pawan Kumar; Pattanayak, Arunava; Reddy, Sokka S.; Gularia, Satish Kumar; Singh, Anju Mahendru; Manjaiah, Kanchikeri Math; Gupta, Hari Shanker

2015-01-01

Deficiency of iron and zinc causes micronutrient malnutrition or hidden hunger, which severely affects ~25% of global population. Genetic biofortification of maize has emerged as cost effective and sustainable approach in addressing malnourishment of iron and zinc deficiency. Therefore, understanding the genetic variation and stability of kernel micronutrients and grain yield of the maize inbreds is a prerequisite in breeding micronutrient-rich high yielding hybrids to alleviate micronutrient malnutrition. We report here, the genetic variability and stability of the kernel micronutrients concentration and grain yield in a set of 50 maize inbred panel selected from the national and the international centres that were raised at six different maize growing regions of India. Phenotyping of kernels using inductively coupled plasma mass spectrometry (ICP-MS) revealed considerable variability for kernel minerals concentration (iron: 18.88 to 47.65 mg kg–1; zinc: 5.41 to 30.85 mg kg–1; manganese: 3.30 to17.73 mg kg–1; copper: 0.53 to 5.48 mg kg–1) and grain yield (826.6 to 5413 kg ha–1). Significant positive correlation was observed between kernel iron and zinc within (r = 0.37 to r = 0.52, p < 0.05) and across locations (r = 0.44, p < 0.01). Variance components of the additive main effects and multiplicative interactions (AMMI) model showed significant genotype and genotype × environment interaction for kernel minerals concentration and grain yield. Most of the variation was contributed by genotype main effect for kernel iron (39.6%), manganese (41.34%) and copper (41.12%), and environment main effects for both kernel zinc (40.5%) and grain yield (37.0%). Genotype main effect plus genotype-by-environment interaction (GGE) biplot identified several mega environments for kernel minerals and grain yield. Comparison of stability parameters revealed AMMI stability value (ASV) as the better representative of the AMMI stability parameters. Dynamic stability parameter GGE distance (GGED) showed strong and positive correlation with both mean kernel concentrations and grain yield. Inbreds (CM-501, SKV-775, HUZM-185) identified from the present investigation will be useful in developing micronutrient-rich as well as stable maize hybrids without compromising grain yield. PMID:26406470

Stability Performance of Inductively Coupled Plasma Mass Spectrometry-Phenotyped Kernel Minerals Concentration and Grain Yield in Maize in Different Agro-Climatic Zones.

PubMed

Mallikarjuna, Mallana Gowdra; Thirunavukkarasu, Nepolean; Hossain, Firoz; Bhat, Jayant S; Jha, Shailendra K; Rathore, Abhishek; Agrawal, Pawan Kumar; Pattanayak, Arunava; Reddy, Sokka S; Gularia, Satish Kumar; Singh, Anju Mahendru; Manjaiah, Kanchikeri Math; Gupta, Hari Shanker

2015-01-01

Deficiency of iron and zinc causes micronutrient malnutrition or hidden hunger, which severely affects ~25% of global population. Genetic biofortification of maize has emerged as cost effective and sustainable approach in addressing malnourishment of iron and zinc deficiency. Therefore, understanding the genetic variation and stability of kernel micronutrients and grain yield of the maize inbreds is a prerequisite in breeding micronutrient-rich high yielding hybrids to alleviate micronutrient malnutrition. We report here, the genetic variability and stability of the kernel micronutrients concentration and grain yield in a set of 50 maize inbred panel selected from the national and the international centres that were raised at six different maize growing regions of India. Phenotyping of kernels using inductively coupled plasma mass spectrometry (ICP-MS) revealed considerable variability for kernel minerals concentration (iron: 18.88 to 47.65 mg kg(-1); zinc: 5.41 to 30.85 mg kg(-1); manganese: 3.30 to 17.73 mg kg(-1); copper: 0.53 to 5.48 mg kg(-1)) and grain yield (826.6 to 5413 kg ha(-1)). Significant positive correlation was observed between kernel iron and zinc within (r = 0.37 to r = 0.52, p < 0.05) and across locations (r = 0.44, p < 0.01). Variance components of the additive main effects and multiplicative interactions (AMMI) model showed significant genotype and genotype × environment interaction for kernel minerals concentration and grain yield. Most of the variation was contributed by genotype main effect for kernel iron (39.6%), manganese (41.34%) and copper (41.12%), and environment main effects for both kernel zinc (40.5%) and grain yield (37.0%). Genotype main effect plus genotype-by-environment interaction (GGE) biplot identified several mega environments for kernel minerals and grain yield. Comparison of stability parameters revealed AMMI stability value (ASV) as the better representative of the AMMI stability parameters. Dynamic stability parameter GGE distance (GGED) showed strong and positive correlation with both mean kernel concentrations and grain yield. Inbreds (CM-501, SKV-775, HUZM-185) identified from the present investigation will be useful in developing micronutrient-rich as well as stable maize hybrids without compromising grain yield.

High throughput SNP discovery and genotyping in grapevine (Vitis vinifera L.) by combining a re-sequencing approach and SNPlex technology

PubMed Central

Lijavetzky, Diego; Cabezas, José Antonio; Ibáñez, Ana; Rodríguez, Virginia; Martínez-Zapater, José M

2007-01-01

Background Single-nucleotide polymorphisms (SNPs) are the most abundant type of DNA sequence polymorphisms. Their higher availability and stability when compared to simple sequence repeats (SSRs) provide enhanced possibilities for genetic and breeding applications such as cultivar identification, construction of genetic maps, the assessment of genetic diversity, the detection of genotype/phenotype associations, or marker-assisted breeding. In addition, the efficiency of these activities can be improved thanks to the ease with which SNP genotyping can be automated. Expressed sequence tags (EST) sequencing projects in grapevine are allowing for the in silico detection of multiple putative sequence polymorphisms within and among a reduced number of cultivars. In parallel, the sequence of the grapevine cultivar Pinot Noir is also providing thousands of polymorphisms present in this highly heterozygous genome. Still the general application of those SNPs requires further validation since their use could be restricted to those specific genotypes. Results In order to develop a large SNP set of wide application in grapevine we followed a systematic re-sequencing approach in a group of 11 grape genotypes corresponding to ancient unrelated cultivars as well as wild plants. Using this approach, we have sequenced 230 gene fragments, what represents the analysis of over 1 Mb of grape DNA sequence. This analysis has allowed the discovery of 1573 SNPs with an average of one SNP every 64 bp (one SNP every 47 bp in non-coding regions and every 69 bp in coding regions). Nucleotide diversity in grape (π = 0.0051) was found to be similar to values observed in highly polymorphic plant species such as maize. The average number of haplotypes per gene sequence was estimated as six, with three haplotypes representing over 83% of the analyzed sequences. Short-range linkage disequilibrium (LD) studies within the analyzed sequences indicate the existence of a rapid decay of LD within the selected grapevine genotypes. To validate the use of the detected polymorphisms in genetic mapping, cultivar identification and genetic diversity studies we have used the SNPlex™ genotyping technology in a sample of grapevine genotypes and segregating progenies. Conclusion These results provide accurate values for nucleotide diversity in coding sequences and a first estimate of short-range LD in grapevine. Using SNPlex™ genotyping we have shown the application of a set of discovered SNPs as molecular markers for cultivar identification, linkage mapping and genetic diversity studies. Thus, the combination a highly efficient re-sequencing approach and the SNPlex™ high throughput genotyping technology provide a powerful tool for grapevine genetic analysis. PMID:18021442

A Slowed Cell Cycle Stabilizes the Budding Yeast Genome.

PubMed

Vinton, Peter J; Weinert, Ted

2017-06-01

During cell division, aberrant DNA structures are detected by regulators called checkpoints that slow division to allow error correction. In addition to checkpoint-induced delay, it is widely assumed, though rarely shown, that merely slowing the cell cycle might allow more time for error detection and correction, thus resulting in a more stable genome. Fidelity by a slowed cell cycle might be independent of checkpoints. Here we tested the hypothesis that a slowed cell cycle stabilizes the genome, independent of checkpoints, in the budding yeast Saccharomyces cerevisiae We were led to this hypothesis when we identified a gene ( ERV14 , an ER cargo membrane protein) that when mutated, unexpectedly stabilized the genome, as measured by three different chromosome assays. After extensive studies of pathways rendered dysfunctional in erv14 mutant cells, we are led to the inference that no particular pathway is involved in stabilization, but rather the slowed cell cycle induced by erv14 stabilized the genome. We then demonstrated that, in genetic mutations and chemical treatments unrelated to ERV14 , a slowed cell cycle indeed correlates with a more stable genome, even in checkpoint-proficient cells. Data suggest a delay in G2/M may commonly stabilize the genome. We conclude that chromosome errors are more rarely made or are more readily corrected when the cell cycle is slowed (even ∼15 min longer in an ∼100-min cell cycle). And, some chromosome errors may not signal checkpoint-mediated responses, or do not sufficiently signal to allow correction, and their correction benefits from this "time checkpoint." Copyright © 2017 by the Genetics Society of America.

Genetic transformation of the yeast Dekkera/Brettanomyces bruxellensis with non-homologous DNA.

PubMed

Miklenić, Marina; Štafa, Anamarija; Bajić, Ana; Žunar, Bojan; Lisnić, Berislav; Svetec, Ivan-Krešimir

2013-05-01

Yeast Dekkera/Brettanomyces bruxellensis is probably the most common contaminant in wineries and ethanol production processes. The considerable economic losses caused by this yeast, but also its ability to produce and tolerate high ethanol concentrations, make it an attractive subject for research with potential for industrial applications. Unfortunately, efforts to understand the biology of D. bruxellensis and facilitate its broader use in industry are hampered by the lack of adequate procedures for delivery of exogenous DNA into this organism. Here we describe the development of transformation protocols (spheroplast transformation, LiAc/PEG method, and electroporation) and report the first genetic transformation of yeast D. bruxellensis. A linear heterologous DNA fragment carrying the kanMX4 sequence was used for transformation, which allowed transformants to be selected on plates containing geneticin. We found the spheroplast transformation method using 1M sorbitol as osmotic stabilizer to be inappropriate because sorbitol strikingly decreases the plating efficiency of both D. bruxellensis spheroplast and intact cells. However, we managed to modify the LiAc/ PEG transformation method and electroporation to accommodate D. bruxellensis transformation, achieving efficiencies of 0.6-16 and 10-20 transformants/microg DNA, respectively. The stability of the transformants ranged from 93.6% to 100%. All putative transformants were analyzed by Southern blot using the kanMX4 sequence as a hybridization probe, which confirmed that the transforming DNA fragment had integrated into the genome. The results of the molecular analysis were consistent with the expected illegitimate integration of a heterologous transforming fragment.

Viability, purity, and genetic stability of entomopathogenic fungi species using different preservation methods.

PubMed

Ayala-Zermeño, Miguel A; Gallou, Adrien; Berlanga-Padilla, Angélica M; Andrade-Michel, Gilda Y; Rodríguez-Rodríguez, José C; Arredondo-Bernal, Hugo C; Montesinos-Matías, Roberto

2017-11-01

Preservation methods for entomopathogenic fungi (EPF) require effective protocols to ensure uniform processes and to avoid alterations during storage. The aim of this study was to preserve Beauveria bassiana, Metarhizium acridum, M. anisopliae, M. rileyi, Isaria javanica, Hirsutella thompsonii, H. citriformis and Lecanicillium lecanii in mineral oil (MO), sterile water (SW), silica gel (SG), lyophilisation (L), ultracold-freezing at -70 °C, and cryopreservation at -196 °C. The viability and purity of the fungi were then verified: phenotypic characteristics were evaluated qualitatively at 6, 12 and 24 m. Genetic stability was tested by amplified fragment length polymorphisms (AFLP) analysis at 24 m. Of the eight species of EPF, three remained viable in SW, five in MO and L, six at -70 °C, seven in SG, and eight at -196 °C. No significant changes were observed in AFLP patterns at 24 m of storage. The most effective preservation methods for EPF were SG, L, -70 and -196 °C. Beauveria bassiana, M. acridum, M. anisopliae, M. rileyi and I. javanica remained stable with all methods, while the remaining species were less compatible. The optimisation of preservation methods for EPF facilitates the development of reliable protocols to ensure their inherent characteristics in culture collections. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Constrained evolution of the sex comb in Drosophila simulans.

PubMed

Maraqa, M S; Griffin, R; Sharma, M D; Wilson, A J; Hunt, J; Hosken, D J; House, C M

2017-02-01

Male fitness is dependent on sexual traits that influence mate acquisition (precopulatory sexual selection) and paternity (post-copulatory sexual selection), and although many studies have documented the form of selection in one or the other of these arenas, fewer have done it for both. Nonetheless, it appears that the dominant form of sexual selection is directional, although theoretically, populations should converge on peaks in the fitness surface, where selection is stabilizing. Many factors, however, can prevent populations from reaching adaptive peaks. Genetic constraints can be important if they prevent the development of highest fitness phenotypes, as can the direction of selection if it reverses across episodes of selection. In this study, we examine the evidence that these processes influence the evolution of the multivariate sex comb morphology of male Drosophila simulans. To do this, we conduct a quantitative genetic study together with a multivariate selection analysis to infer how the genetic architecture and selection interact. We find abundant genetic variance and covariance in elements of the sex comb. However, there was little evidence for directional selection in either arena. Significant nonlinear selection was detected prior to copulation when males were mated to nonvirgin females, and post-copulation during sperm offence (again with males mated to nonvirgins). Thus, contrary to our predictions, the evolution of the D. simulans sex comb is limited neither by genetic constraints nor by antagonistic selection between pre- and post-copulatory arenas, but nonlinear selection on the multivariate phenotype may prevent sex combs from evolving to reach some fitness maximizing optima. © 2016 The Authors. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Aggression and Rule-breaking: Heritability and stability of antisocial behavior problems in childhood and adolescence

PubMed Central

Niv, Sharon; Tuvblad, Catherine; Raine, Adrian; Baker, Laura A.

2013-01-01

Purpose This twin study examined the structure of genetic and environmental influences on aggression and rule-breaking in order to examine change and stability across the span of childhood to mid-adolescence. Methods Behavioral assessments were conducted at two time points: age 9–10 years and 14–15 years. Using behavioral genetics biometric modeling, the longitudinal structure of influences was investigated. Results Aggression and rule-breaking were found to be influenced by a latent common factor of antisocial behavior (ASB) within each wave of data collection. The childhood-age common factor of ASB was influenced by 41% genetics, 40% shared environment and 19% nonshared environment. In adolescence, 41% of influences on the common factor were novel and entirely genetic, while the remainder of influences were stable across time. Additionally, both aggression and rule-breaking within each wave were found to have unique influences not common across subscales or across waves, highlighting specificity of influences on different problem behaviors at both ages. Conclusions This research sheds light on the commonality of influences on etiology of different forms of antisocial behavior, and suggests future directions for research into intervention for antisocial behavior problems in youth, such as investigation of adolescence-specific environmental influences on the development of antisocial behavior problems. PMID:24347737

Mitochondria damage checkpoint in apoptosis and genome stability.

PubMed

Singh, Keshav K

2004-11-01

Mitochondria perform multiple cellular functions including energy production, cell proliferation and apoptosis. Studies described in this paper suggest a role for mitochondria in maintaining genomic stability. Genomic stability appears to be dependent on mitochondrial functions involved in maintenance of proper intracellular redox status, ATP-dependent transcription, DNA replication, DNA repair and DNA recombination. To further elucidate the role of mitochondria in genomic stability, I propose a mitochondria damage checkpoint (mitocheckpoint) that monitors and responds to damaged mitochondria. Mitocheckpoint can coordinate and maintain proper balance between apoptotic and anti-apoptotic signals. When mitochondria are damaged, mitocheckpoint can be activated to help cells repair damaged mitochondria, to restore normal mitochondrial function and avoid production of mitochondria-defective cells. If mitochondria are severely damaged, mitocheckpoint may not be able to repair the damage and protect cells. Such an event triggers apoptosis. If damage to mitochondria is continuous or persistent such as damage to mitochondrial DNA resulting in mutations, mitocheckpoint may fail which can lead to genomic instability and increased cell survival in yeast. In human it can cause cancer. In support of this proposal we provide evidence that mitochondrial genetic defects in both yeast and mammalian systems lead to impaired DNA repair, increased genomic instability and increased cell survival. This study reveals molecular genetic mechanisms underlying a role for mitochondria in carcinogenesis in humans.

[Association between patatin-like phospholipase domain-containing protein 3 gene rs738409 polymorphism and non-alcoholic fatty liver disease susceptibility: a meta-analysis].

PubMed

Wu, Pengbo; Shu, Yongxiang; Guo, Fang; Luo, Hesheng; Zhang, Guo; Tan, Shiyun

2015-01-01

To explore the association between patatin-like phospholipase domain-containing protein 3(PNPLA3) gene rs738409 polymorphism and the susceptibility of non-alcoholic fatty liver disease(NAFLD). Data bases were comprehensively searched to retrace all the related studies on the association between PNPLA3 gene rs738409 polymorphism and susceptibility. Of NAFLD, the pooled OR with 95% CI of the association between PNPLA3 gene rs738409 polymorphism and NAFLD susceptibility were performed using different genetic models. Subgroup analysis based on the source of population and sensitivity analysis was performed to detect the stability of results. 28 original studies with 6 216 patients and 8 218 controls were involved in the final combination of data. Findings from the meta-analyses showed that there were strong associations between PNPLA3 gene rs738409 polymorphism and the susceptibility of NAFLD, under different genetic model comparisons[GG vs. CC:OR = 2.42, 95%CI:1.83-3.21, P < 0.001;CG vs. CC:OR = 1.28, 95%CI:1.15-1.43, P < 0.001;CG+GG vs. CC:OR = 1.31, 95%CI:1.17-1.46, P < 0.001; GG vs. CC+GC:OR = 2.26, 95%CI:1.76-2.90, P < 0.001]. Similar results were found in both Asian and Caucasian populations. Results from the Meta-analysis strongly suggested that there appeared significant association between PNPLA3 gene rs738409 polymorphism and the susceptibility of NAFLD.

The Complete Chloroplast Genome Sequence of a Relict Conifer Glyptostrobus pensilis: Comparative Analysis and Insights into Dynamics of Chloroplast Genome Rearrangement in Cupressophytes and Pinaceae

PubMed Central

Zheng, Renhua; Xu, Haibin; Zhou, Yanwei; Li, Meiping; Lu, Fengjuan; Dong, Yini; Liu, Xin; Chen, Jinhui; Shi, Jisen

2016-01-01

Glyptostrobus pensilis, belonging to the monotypic genus Glyptostrobus (Family: Cupressaceae), is an ancient conifer that is naturally distributed in low-lying wet areas. Here, we report the complete chloroplast (cp) genome sequence (132,239 bp) of G. pensilis. The G. pensilis cp genome is similar in gene content, organization and genome structure to the sequenced cp genomes from other cupressophytes, especially with respect to the loss of the inverted repeat region A (IRA). Through phylogenetic analysis, we demonstrated that the genus Glyptostrobus is closely related to the genus Cryptomeria, supporting previous findings based on physiological characteristics. Since IRs play an important role in stabilize cp genome and conifer cp genomes lost different IR regions after splitting in two clades (cupressophytes and Pinaceae), we performed cp genome rearrangement analysis and found more extensive cp genome rearrangements among the species of cupressophytes relative to Pinaceae. Additional repeat analysis indicated that cupressophytes cp genomes contained less potential functional repeats, especially in Cupressaceae, compared with Pinaceae. These results suggested that dynamics of cp genome rearrangement in conifers differed since the two clades, Pinaceae and cupressophytes, lost IR copies independently and developed different repeats to complement the residual IRs. In addition, we identified 170 perfect simple sequence repeats that will be useful in future research focusing on the evolution of genetic diversity and conservation of genetic variation for this endangered species in the wild. PMID:27560965

Optimal Robust Motion Controller Design Using Multiobjective Genetic Algorithm

PubMed Central

Svečko, Rajko

2014-01-01

This paper describes the use of a multiobjective genetic algorithm for robust motion controller design. Motion controller structure is based on a disturbance observer in an RIC framework. The RIC approach is presented in the form with internal and external feedback loops, in which an internal disturbance rejection controller and an external performance controller must be synthesised. This paper involves novel objectives for robustness and performance assessments for such an approach. Objective functions for the robustness property of RIC are based on simple even polynomials with nonnegativity conditions. Regional pole placement method is presented with the aims of controllers' structures simplification and their additional arbitrary selection. Regional pole placement involves arbitrary selection of central polynomials for both loops, with additional admissible region of the optimized pole location. Polynomial deviation between selected and optimized polynomials is measured with derived performance objective functions. A multiobjective function is composed of different unrelated criteria such as robust stability, controllers' stability, and time-performance indexes of closed loops. The design of controllers and multiobjective optimization procedure involve a set of the objectives, which are optimized simultaneously with a genetic algorithm—differential evolution. PMID:24987749

Genetic information and ecosystem health: arguments for the application of chaos theory to identify boundary conditions for ecosystem management.

PubMed Central

Stomp, A M

1994-01-01

To meet the demands for goods and services of an exponentially growing human population, global ecosystems will come under increasing human management. The hallmark of successful ecosystem management will be long-term ecosystem stability. Ecosystems and the genetic information and processes which underlie interactions of organisms with the environment in populations and communities exhibit behaviors which have nonlinear characteristics. Nonlinear mathematical formulations describing deterministic chaos have been used successfully to model such systems in physics, chemistry, economics, physiology, and epidemiology. This approach can be extended to ecotoxicology and can be used to investigate how changes in genetic information determine the behavior of populations and communities. This article seeks to provide the arguments for such an approach and to give initial direction to the search for the boundary conditions within which lies ecosystem stability. The identification of a theoretical framework for ecotoxicology and the parameters which drive the underlying model is a critical component in the formulation of a prioritized research agenda and appropriate ecosystem management policy and regulation. PMID:7713038

ATM Mediates pRB Function To Control DNMT1 Protein Stability and DNA Methylation

PubMed Central

Suzuki, Misa; Hayashi, Naoyuki; Kobayashi, Masahiko; Sasaki, Nobunari; Nishiuchi, Takumi; Doki, Yuichiro; Okamoto, Takahiro; Kohno, Susumu; Muranaka, Hayato; Kitajima, Shunsuke; Yamamoto, Ken-ichi

2013-01-01

The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. PMID:23754744

Support vector regression and artificial neural network models for stability indicating analysis of mebeverine hydrochloride and sulpiride mixtures in pharmaceutical preparation: A comparative study

NASA Astrophysics Data System (ADS)

Naguib, Ibrahim A.; Darwish, Hany W.

2012-02-01

A comparison between support vector regression (SVR) and Artificial Neural Networks (ANNs) multivariate regression methods is established showing the underlying algorithm for each and making a comparison between them to indicate the inherent advantages and limitations. In this paper we compare SVR to ANN with and without variable selection procedure (genetic algorithm (GA)). To project the comparison in a sensible way, the methods are used for the stability indicating quantitative analysis of mixtures of mebeverine hydrochloride and sulpiride in binary mixtures as a case study in presence of their reported impurities and degradation products (summing up to 6 components) in raw materials and pharmaceutical dosage form via handling the UV spectral data. For proper analysis, a 6 factor 5 level experimental design was established resulting in a training set of 25 mixtures containing different ratios of the interfering species. An independent test set consisting of 5 mixtures was used to validate the prediction ability of the suggested models. The proposed methods (linear SVR (without GA) and linear GA-ANN) were successfully applied to the analysis of pharmaceutical tablets containing mebeverine hydrochloride and sulpiride mixtures. The results manifest the problem of nonlinearity and how models like the SVR and ANN can handle it. The methods indicate the ability of the mentioned multivariate calibration models to deconvolute the highly overlapped UV spectra of the 6 components' mixtures, yet using cheap and easy to handle instruments like the UV spectrophotometer.

Cell-cell bioelectrical interactions and local heterogeneities in genetic networks: a model for the stabilization of single-cell states and multicellular oscillations.

PubMed

Cervera, Javier; Manzanares, José A; Mafe, Salvador

2018-04-04

Genetic networks operate in the presence of local heterogeneities in single-cell transcription and translation rates. Bioelectrical networks and spatio-temporal maps of cell electric potentials can influence multicellular ensembles. Could cell-cell bioelectrical interactions mediated by intercellular gap junctions contribute to the stabilization of multicellular states against local genetic heterogeneities? We theoretically analyze this question on the basis of two well-established experimental facts: (i) the membrane potential is a reliable read-out of the single-cell electrical state and (ii) when the cells are coupled together, their individual cell potentials can be influenced by ensemble-averaged electrical potentials. We propose a minimal biophysical model for the coupling between genetic and bioelectrical networks that associates the local changes occurring in the transcription and translation rates of an ion channel protein with abnormally low (depolarized) cell potentials. We then analyze the conditions under which the depolarization of a small region (patch) in a multicellular ensemble can be reverted by its bioelectrical coupling with the (normally polarized) neighboring cells. We show also that the coupling between genetic and bioelectric networks of non-excitable cells, modulated by average electric potentials at the multicellular ensemble level, can produce oscillatory phenomena. The simulations show the importance of single-cell potentials characteristic of polarized and depolarized states, the relative sizes of the abnormally polarized patch and the rest of the normally polarized ensemble, and intercellular coupling.

Interactions between Multiple Genetic Determinants in the 5′ UTR and VP1 Capsid Control Pathogenesis of Chronic Post-Viral Myopathy caused by Coxsackievirus B1

PubMed Central

Sandager, Maribeth M.; Nugent, Jaime L.; Schulz, Wade L.; Messner, Ronald P.; Tam, Patricia E.

2008-01-01

Mice infected with coxsackievirus B1 Tucson (CVB1T) develop chronic, post-viral myopathy (PVM) with clinical manifestations of hind limb muscle weakness and myositis. The objective of the current study was to establish the genetic basis of myopathogenicity in CVB1T. Using a reverse genetics approach, full attenuation of PVM could only be achieved by simultaneously mutating four sites located at C706U in the 5′ untranslated region (5′ UTR) and at Y87F, V136A, and T276A in the VP1 capsid. Engineering these four myopathic determinants into an amyopathic CVB1T variant restored the ability to cause PVM. Moreover, these same four determinants controlled PVM expression in a second strain of mice, indicating that the underlying mechanism is operational in mice of different genetic backgrounds. Modeling studies predict that C706U alters both local and long-range pairing in the 5′ UTR, and that VP1 determinants are located on the capsid surface. However, these differences did not affect viral titers, temperature stability, pH stability, or the antibody response to virus. These studies demonstrate that PVM develops from a complex interplay between viral determinants in the 5′ UTR and VP1 capsid and have uncovered intriguing similarities between genetic determinants that cause PVM and those involved in pathogenesis of other enteroviruses. PMID:18029287

[Selection of reference genes of Siraitia grosvenorii by real-time PCR].

PubMed

Tu, Dong-ping; Mo, Chang-ming; Ma, Xiao-jun; Zhao, Huan; Tang, Qi; Huang, Jie; Pan, Li-mei; Wei, Rong-chang

2015-01-01

Siraitia grosvenorii is a traditional Chinese medicine also as edible food. This study selected six candidate reference genes by real-time quantitative PCR, the expression stability of the candidate reference genes in the different samples was analyzed by using the software and methods of geNorm, NormFinder, BestKeeper, Delta CT method and RefFinder, reference genes for S. grosvenorii were selected for the first time. The results showed that 18SrRNA expressed most stable in all samples, was the best reference gene in the genetic analysis. The study has a guiding role for the analysis of gene expression using qRT-PCR methods, providing a suitable reference genes to ensure the results in the study on differential expressed gene in synthesis and biological pathways, also other genes of S. grosvenorii.

[Single-nucleotide polymorphism in populations of sockeye salmon Oncorhynchus nerka from Kamchatka Peninsula].

PubMed

Khrustaleva, A M; Gritsenko, O F; Klovach, N V

2013-11-01

The genetic polymorphism of 45 single-nucleotide polymorphism loci was examined in the four largest wild populations of sockeye salmon Oncorhynchusnerka from drainages of the Asian coast of the Pacific Ocean (Eastern and Western Kamchatka). It was demonstrated that sockeye salmon from the Palana River were considerably different from all other populations examined. The most probable explanation of the observed differences is the suggestion on possible demographic events in the history of this population associated with the decrease in its effective number. To study the origin, colonization patterns, and evolution of Asian sockeye salmon, as well as to resolve some of the applied tasks, like population assignment and genetic identification, a differentiation approach to SNP-marker selection was suggested. Adaptively important loci that evolve under the pressure of balancing (stabilizing) selection were identified, thanks to which the number of loci that provide the baseline classification error rates in the population assignment tests was reduced to 30. It was demonstrated that SNPs located in the MHC2 and GPH genes were affected by diversifying selection. Procedures for selecting single-nucleotide polymorphisms for phylogenetic studies of Asian sockeye salmon were suggested. Using principal-component analysis, 17 loci that adequately reproduce genetic differentiation within arid among the regions of the origin of Kamchatka sockeye salmon, were selected.

Subchronic toxicity study in vivo and allergenicity study in vitro for genetically modified rice that expresses pharmaceutical protein (human serum albumin).

PubMed

Sheng, Yao; Qi, Xiaozhe; Liu, Yifei; Guo, Mingzhang; Chen, Siyuan; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2014-10-01

Genetically modified (GM) crops that express pharmaceutical proteins have become an important focus of recent genetic engineering research. Food safety assessment is necessary for the commercial development of these crops. Subchronic toxicity study in vivo and allergenicity study in vitro were designed to evaluate the food safety of the rice variety expressing human serum albumin (HSA). Animals were fed rodent diets containing 12.5%, 25.0% and 50.0% GM or non-GM rice for 90 days. The composition analysis of the GM rice demonstrated several significant differences. However, most of the differences remained within the ranges reported in the literature. In the animal study, a range of indexes including clinical observation, feed efficiency, hematology, serum chemistry, organ weights and histopathology were examined. Random changes unrelated to the GM rice exposure, within the range of historical control values and not associated with any signs of illness were observed. The results of heat stability and in vitro digestion of HSA indicated no evidence of potential allergenicity of the protein. Overall, the results of these studies suggest that the GM rice appears to be safe as a dietary ingredient when it is used at up to 50% in the diet on a subchronic basis. Copyright © 2014 Elsevier Ltd. All rights reserved.

A genetically encoded fluorescent tRNA is active in live-cell protein synthesis

PubMed Central

Masuda, Isao; Igarashi, Takao; Sakaguchi, Reiko; Nitharwal, Ram G.; Takase, Ryuichi; Han, Kyu Young; Leslie, Benjamin J.; Liu, Cuiping; Gamper, Howard; Ha, Taekjip; Sanyal, Suparna

2017-01-01

Abstract Transfer RNAs (tRNAs) perform essential tasks for all living cells. They are major components of the ribosomal machinery for protein synthesis and they also serve in non-ribosomal pathways for regulation and signaling metabolism. We describe the development of a genetically encoded fluorescent tRNA fusion with the potential for imaging in live Escherichia coli cells. This tRNA fusion carries a Spinach aptamer that becomes fluorescent upon binding of a cell-permeable and non-toxic fluorophore. We show that, despite having a structural framework significantly larger than any natural tRNA species, this fusion is a viable probe for monitoring tRNA stability in a cellular quality control mechanism that degrades structurally damaged tRNA. Importantly, this fusion is active in E. coli live-cell protein synthesis allowing peptidyl transfer at a rate sufficient to support cell growth, indicating that it is accommodated by translating ribosomes. Imaging analysis shows that this fusion and ribosomes are both excluded from the nucleoid, indicating that the fusion and ribosomes are in the cytosol together possibly engaged in protein synthesis. This fusion methodology has the potential for developing new tools for live-cell imaging of tRNA with the unique advantage of both stoichiometric labeling and broader application to all cells amenable to genetic engineering. PMID:27956502

Longitudinal Stability of Genetic and Environmental Influences on the Association between Diurnal Preference and Sleep Quality in Young Adult Twins and Siblings.

PubMed

Barclay, Nicola L; Rowe, Richard; O'Leary, Rachael; Bream, Danielle; Gregory, Alice M

2016-08-01

Overlapping genetic influences have been implicated in diurnal preference and subjective sleep quality. Our overall aim was to examine overlapping concurrent and longitudinal genetic and environmental effects on diurnal preference and sleep quality over ~5 years. Behavioral genetic analyses were performed on data from the longitudinal British G1219 study of young adult twins and nontwin siblings. A total of 1556 twins and siblings provided data on diurnal preference (Morningness-Eveningness Questionnaire) and sleep quality (Pittsburgh Sleep Quality Index) at time 1 (mean age = 20.30 years, SD = 1.76; 62% female), and 862 participated at time 2 (mean age = 25.30 years, SD = 1.81; 66% female). Preference for eveningness was associated with poorer sleep quality at both time points (r = 0.25 [95% confidence intervals {CIs} = 0.20-0.30] and r = 0.21 [CI = 0.15-0.28]). There was substantial overlap in the genetic influences on diurnal preference and sleep quality individually, across time (genetic correlations [rAs]: 0.64 [95% CI = 0.59-0.67] and 0.48 [95% CI = 0.42-.053]). There were moderate genetic correlations between diurnal preference and sleep quality concurrently and longitudinally (rAs = 0.29-0.60). Nonshared environmental overlap was substantially smaller for all cross-phenotype associations (nonshared environmental correlations (rEs) = -0.02 to 0.08). All concurrent and longitudinal associations within and between phenotypes were largely accounted for by genetic factors (explaining between 60% and 100% of the associations). All shared environmental effects were nonsignificant. Nonshared environmental influences played a smaller role on the associations between phenotypes (explaining between -0.06% and 40% of the associations). These results suggest that to some extent, similar genes contribute to the stability of diurnal preference and sleep quality throughout young adulthood but also that different genes play a part over this relatively short time frame. While there was evidence of genetic overlap between phenotypes concurrently and longitudinally, the possible emergence of new genetic factors (or decline of previously associated factors) suggests that molecular genetic studies focusing on young adults should consider more tightly specified age groups, given that genetic effects may be time specific. © 2016 The Author(s).

Geomorphological and sedimentological analysis of flash-flood deposits: The case of the 1997 Rivillas flood (Spain)

NASA Astrophysics Data System (ADS)

Ortega, Jose A.; Garzón Heydt, Guillermina

2009-11-01

On the basis of the description of the 1997 Rivillas flood deposits, a morphosedimentary feature classification is proposed. Mapping of the main morphosedimentary deposits in seven reaches along the basin has provided abundant data for each defined typology and for a better adjustment of their stability fields. Because of their unstable preservation environment, immediate post-flood field surveys with descriptions of erosive and depositional features were undertaken. Up to 18 features were classified as either sedimentary or erosive and mapped according to their genetic environments. Anthropic interference such as land use changes produce modification of sediment supply and in channel and floodplain erosive processes causing flash-floods to be more catastrophic. Erosive features are dominant over sedimentary ones, as the sedimentary budget in the river is negative. By means of HEC-RAS (Hydrologic Engineering Center) modelling, we were able to obtain mean values of the main variables limiting feature stability (velocity, depth, stream powers and shear stress). These provide information regarding maximum stability threshold and peak flood discharge. The ephemeral nature of riverine flash-flood deposits in this type of setting does not mean that they are not significant, and their interpretation after recent floods can significantly improve interpretation of the event dynamics and its flood hydrology and also be useful for flood risk mapping.

Genetics Home Reference: dystrophic epidermolysis bullosa

MedlinePlus

... protein that is used to assemble type VII collagen. Collagens are molecules that give structure and strength to ... tendons, and ligaments, throughout the body. Type VII collagen plays an important role in strengthening and stabilizing ...

What is microbial community ecology?

PubMed

Konopka, Allan

2009-11-01

The activities of complex communities of microbes affect biogeochemical transformations in natural, managed and engineered ecosystems. Meaningfully defining what constitutes a community of interacting microbial populations is not trivial, but is important for rigorous progress in the field. Important elements of research in microbial community ecology include the analysis of functional pathways for nutrient resource and energy flows, mechanistic understanding of interactions between microbial populations and their environment, and the emergent properties of the complex community. Some emergent properties mirror those analyzed by community ecologists who study plants and animals: biological diversity, functional redundancy and system stability. However, because microbes possess mechanisms for the horizontal transfer of genetic information, the metagenome may also be considered as a community property.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konopka, Allan

The activities of complex communities of microbes affect biogeochemical transformations in natural, managed and engineered ecosystems. Meaningfully defining what constitutes a community of interacting microbial populations is not trivial, but is important for rigorous progress in the field. Important elements of research in microbial community ecology include the analysis of functional pathways for nutrient resource and energy flows, mechanistic understanding of interactions between microbial populations and their environment, and the emergent properties of the complex community. Some emergent properties mirror those analyzed by community ecologists who study plants and animals: biological diversity, functional redundancy and system stability. However, because microbesmore » possess mechanisms for the horizontal transfer of genetic information, the metagenome may also be considered a community property.« less

Wnt-Spectrum Vitreoretinopathy Masquerading as Congenital Toxoplasmosis.

PubMed

Callaway, Natalia F; Berrocal, Audina M

2018-06-01

Wnt-spectrum vitreoretinopathies are a group of rare inherited disorders of retinal angiogenesis that include familial exudative vitreoretinopathy/Norrie disease and are most commonly autosomal dominant; however, they can rarely present with other inheritance patterns that are more difficult to diagnose. The authors describe a case of an uncle misdiagnosed as congenital toxoplasmosis for decades and his 2-month-old nephew presenting with bilateral retinal detachments. Genetic analysis revealed an NDP gene mutation in the child and the uncle, as well as heterozygosity of the mother confirming a Wnt-spectrum vitreoretinopathy. This report describes the evaluation, diagnosis, and importance of early laser stabilization of this disorder. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:446-450.]. Copyright 2018, SLACK Incorporated.

Regulation of Replication Fork Advance and Stability by Nucleosome Assembly

PubMed Central

Prado, Felix; Maya, Douglas

2017-01-01

The advance of replication forks to duplicate chromosomes in dividing cells requires the disassembly of nucleosomes ahead of the fork and the rapid assembly of parental and de novo histones at the newly synthesized strands behind the fork. Replication-coupled chromatin assembly provides a unique opportunity to regulate fork advance and stability. Through post-translational histone modifications and tightly regulated physical and genetic interactions between chromatin assembly factors and replisome components, chromatin assembly: (1) controls the rate of DNA synthesis and adjusts it to histone availability; (2) provides a mechanism to protect the integrity of the advancing fork; and (3) regulates the mechanisms of DNA damage tolerance in response to replication-blocking lesions. Uncoupling DNA synthesis from nucleosome assembly has deleterious effects on genome integrity and cell cycle progression and is linked to genetic diseases, cancer, and aging. PMID:28125036

Why it is hard to find genes associated with social science traits: theoretical and empirical considerations.

PubMed

Chabris, Christopher F; Lee, James J; Benjamin, Daniel J; Beauchamp, Jonathan P; Glaeser, Edward L; Borst, Gregoire; Pinker, Steven; Laibson, David I

2013-10-01

We explain why traits of interest to behavioral scientists may have a genetic architecture featuring hundreds or thousands of loci with tiny individual effects rather than a few with large effects and why such an architecture makes it difficult to find robust associations between traits and genes. We conducted a genome-wide association study at 2 sites, Harvard University and Union College, measuring more than 100 physical and behavioral traits with a sample size typical of candidate gene studies. We evaluated predictions that alleles with large effect sizes would be rare and most traits of interest to social science are likely characterized by a lack of strong directional selection. We also carried out a theoretical analysis of the genetic architecture of traits based on R.A. Fisher's geometric model of natural selection and empirical analyses of the effects of selection bias and phenotype measurement stability on the results of genetic association studies. Although we replicated several known genetic associations with physical traits, we found only 2 associations with behavioral traits that met the nominal genome-wide significance threshold, indicating that physical and behavioral traits are mainly affected by numerous genes with small effects. The challenge for social science genomics is the likelihood that genes are connected to behavioral variation by lengthy, nonlinear, interactive causal chains, and unraveling these chains requires allying with personal genomics to take advantage of the potential for large sample sizes as well as continuing with traditional epidemiological studies.

Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy.

PubMed

Estrada, J C; Torres, Y; Benguría, A; Dopazo, A; Roche, E; Carrera-Quintanar, L; Pérez, R A; Enríquez, J A; Torres, R; Ramírez, J C; Samper, E; Bernad, A

2013-06-27

In most clinical trials, human mesenchymal stem cells (hMSCs) are expanded in vitro before implantation. The genetic stability of human stem cells is critical for their clinical use. However, the relationship between stem-cell expansion and genetic stability is poorly understood. Here, we demonstrate that within the normal expansion period, hMSC cultures show a high percentage of aneuploid cells that progressively increases until senescence. Despite this accumulation, we show that in a heterogeneous culture the senescence-prone hMSC subpopulation has a lower proliferation potential and a higher incidence of aneuploidy than the non-senescent subpopulation. We further show that senescence is linked to a novel transcriptional signature that includes a set of genes implicated in ploidy control. Overexpression of the telomerase catalytic subunit (human telomerase reverse transcriptase, hTERT) inhibited senescence, markedly reducing the levels of aneuploidy and preventing the dysregulation of ploidy-controlling genes. hMSC-replicative senescence was accompanied by an increase in oxygen consumption rate (OCR) and oxidative stress, but in long-term cultures that overexpress hTERT, these parameters were maintained at basal levels, comparable to unmodified hMSCs at initial passages. We therefore propose that hTERT contributes to genetic stability through its classical telomere maintenance function and also by reducing the levels of oxidative stress, possibly, by controlling mitochondrial physiology. Finally, we propose that aneuploidy is a relevant factor in the induction of senescence and should be assessed in hMSCs before their clinical use.

Floral trait variation and integration as a function of sexual deception in Gorteria diffusa.

PubMed

Ellis, Allan G; Brockington, Samuel F; de Jager, Marinus L; Mellers, Gregory; Walker, Rachel H; Glover, Beverley J

2014-08-19

Phenotypic integration, the coordinated covariance of suites of morphological traits, is critical for proper functioning of organisms. Angiosperm flowers are complex structures comprising suites of traits that function together to achieve effective pollen transfer. Floral integration could reflect shared genetic and developmental control of these traits, or could arise through pollinator-imposed stabilizing correlational selection on traits. We sought to expose mechanisms underlying floral trait integration in the sexually deceptive daisy, Gorteria diffusa, by testing the hypothesis that stabilizing selection imposed by male pollinators on floral traits involved in mimicry has resulted in tighter integration. To do this, we quantified patterns of floral trait variance and covariance in morphologically divergent G. diffusa floral forms representing a continuum in the levels of sexual deception. We show that integration of traits functioning in visual attraction of male pollinators increases with pollinator deception, and is stronger than integration of non-mimicry trait modules. Consistent patterns of within-population trait variance and covariance across floral forms suggest that integration has not been built by stabilizing correlational selection on genetically independent traits. Instead pollinator specialization has selected for tightened integration within modules of linked traits. Despite potentially strong constraint on morphological evolution imposed by developmental genetic linkages between traits, we demonstrate substantial divergence in traits across G. diffusa floral forms and show that divergence has often occurred without altering within-population patterns of trait correlations. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His.

PubMed

Jiang, Yan; Su, Jing-Tan; Zhang, Jun; Wei, Xiang; Yan, Yong-Bin; Zhou, Hai-Meng

2008-01-01

Human carbonic anhydrase (HCA) II participates in a variety of important biological processes, and it has long been known that genetic mutations of HCA II are closely correlated to human disease. In this research, we investigated the effects of a genetic single point mutation P237, which is located on the surface of the molecule and does not participate in the HCA II catalysis, on HCA II activity, stability and folding. Spectroscopic studies revealed that the mutation caused more buried Trp residues to become accessible by solvent and caused the NMR signals to become less dispersed, but did not affect the secondary structure or the hydrophobic exposure of the protein. The mutant was less stable than the wild type enzyme against heat- and GdnHCl-induced inactivation, but its pH adaptation was similar to the wild type. The mutation slightly decreased the stability of the molten globular intermediate, but gradually affected the stability of the native state by a 10-fold reduction of the Gibbs free energy for the transition from the native state to the intermediate. This might have led to an accumulation of the aggregation-prone molten globular intermediate, which further trapped the proteins into the off-pathway aggregates during refolding and reduced the levels of active enzyme in vivo. The results herein suggested that the correct positioning of the long loop around P237 might be crucial to the folding of HCA II, particularly the formation of the active site.

Evidence for a lineage of virulent bacteriophages that target Campylobacter.

PubMed

Timms, Andrew R; Cambray-Young, Joanna; Scott, Andrew E; Petty, Nicola K; Connerton, Phillippa L; Clarke, Louise; Seeger, Kathy; Quail, Mike; Cummings, Nicola; Maskell, Duncan J; Thomson, Nicholas R; Connerton, Ian F

2010-03-30

Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S-adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other Campylobacter bacteriophages, forming a highly conserved lineage of bacteriophages that predate upon campylobacters and indicating that highly adapted bacteriophage genomes can be stable over prolonged periods of time.

SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability.

PubMed

Scott, Katherine A; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E; Stuart, David I; Charleston, Bryan; Maree, Francois F

2017-05-15

Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses. Copyright © 2017 American Society for Microbiology.

SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability

PubMed Central

Scott, Katherine A.; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E.; Stuart, David I.; Charleston, Bryan

2017-01-01

ABSTRACT Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses. PMID:28298597

Consequences of the genetic threshold model for observing partial migration under climate change scenarios.

PubMed

Cobben, Marleen M P; van Noordwijk, Arie J

2017-10-01

Migration is a widespread phenomenon across the animal kingdom as a response to seasonality in environmental conditions. Partially migratory populations are populations that consist of both migratory and residential individuals. Such populations are very common, yet their stability has long been debated. The inheritance of migratory activity is currently best described by the threshold model of quantitative genetics. The inclusion of such a genetic threshold model for migratory behavior leads to a stable zone in time and space of partially migratory populations under a wide range of demographic parameter values, when assuming stable environmental conditions and unlimited genetic diversity. Migratory species are expected to be particularly sensitive to global warming, as arrival at the breeding grounds might be increasingly mistimed as a result of the uncoupling of long-used cues and actual environmental conditions, with decreasing reproduction as a consequence. Here, we investigate the consequences for migratory behavior and the stability of partially migratory populations under five climate change scenarios and the assumption of a genetic threshold value for migratory behavior in an individual-based model. The results show a spatially and temporally stable zone of partially migratory populations after different lengths of time in all scenarios. In the scenarios in which the species expands its range from a particular set of starting populations, the genetic diversity and location at initialization determine the species' colonization speed across the zone of partial migration and therefore across the entire landscape. Abruptly changing environmental conditions after model initialization never caused a qualitative change in phenotype distributions, or complete extinction. This suggests that climate change-induced shifts in species' ranges as well as changes in survival probabilities and reproductive success can be met with flexibility in migratory behavior at the species level, which will reduce the risk of extinction.

An Evolutionarily Conserved Family of Virion Tail Needles Related to Bacteriophage P22 gp26: Correlation between Structural Stability and Length of the -Helical Trimeric Coiled Coil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhardwaj, A.; Walker-Kopp, N; Casjens, S

2009-01-01

Bacteriophages of the Podoviridae family use short noncontractile tails to inject their genetic material into Gram-negative bacteria. In phage P22, the tail contains a thin needle, encoded by the phage gene 26, which is essential both for stabilization and for ejection of the packaged viral genome. Bioinformatic analysis of the N-terminal domain of gp26 (residues 1-60) led us to identify a family of genes encoding putative homologues of the tail needle gp26. To validate this idea experimentally and to explore their diversity, we cloned the gp26-like gene from phages HK620, Sf6 and HS1, and characterized these gene products in solution.more » All gp26-like factors contain an elongated {alpha}-helical coiled-coil core consisting of repeating, adjacent trimerization heptads and form trimeric fibers with length ranging between about 240 to 300 {angstrom}. gp26 tail needles display a high level of structural stability in solution, with Tm (temperature of melting) between 85 and 95 C. To determine how the structural stability of these phage fibers correlates with the length of the {alpha}-helical core, we investigated the effect of insertions and deletions in the helical core. In the P22 tail needle, we identified an 85-residue-long helical domain, termed MiCRU (minimal coiled-coil repeat unit), that can be inserted in-frame inside the gp26 helical core, preserving the straight morphology of the fiber. Likewise, we were able to remove three quarters of the helical core of the HS1 tail needle, minimally decreasing the stability of the fiber. We conclude that in the gp26 family of tail needles, structural stability increases nonlinearly with the length of the {alpha}-helical core. Thus, the overall stability of these bacteriophage fibers is not solely dependent on the number of trimerization repeats in the {alpha}-helical core.« less

Seed-Specific Stable Expression of the α-AI1 Inhibitor in Coffee Grains and the In Vivo Implications for the Development of the Coffee Berry Borer.

PubMed

Albuquerque, Érika V S; Bezerra, Caroline A; Romero, Juan V; Valencia, Jorge W A; Valencia-Jiménez, Arnubio; Pimenta, Lucas M; Barbosa, Aulus E A D; Silva, Maria C M; Meneguim, Ana M; Sá, Maria Eugênia L; Engler, Gilbert; de Almeida-Engler, Janice; Fernandez, Diana; Grossi-de-Sá, Maria F

Genetic transformation of coffee ( Coffea spp.), the second most traded commodity worldwide, is an alternative approach to introducing features that cannot be introgressed by traditional crossings. The transgenic stability, heritability and quantitative and spatial expression patterns of the seed-specific promoter phytohemagglutinin (PHA-L) from Phaseolus vulgaris were characterized in genetically modified C. arabica expressing the α-amylase inhibitor-1 ( α-AI1 ) gene. The α-AI1 inhibitor shows considerable activity toward digestive enzymes of the coffee berry borer (CBB) Hypothenemus hampei . This insect pest expends its life cycle almost entirely in coffee berries. Transgene containment in the fruit is important to meeting food and environmental safety requirements for releasing genetically modified (GM) crops. PCR analysis of T2 coffee plants showed a Mendelian single-copy segregation pattern. Ectopic transgene expression was only detected in coffee grains, as demonstrated by reverse transcription-PCR analysis of different plant tissues. An intense immunocytochemical signal associated with α-AI1 protein expression was localized to endospermic cells. In addition, a delay in the larval development of CBB was observed after challenging transgenic coffee seeds with the insect. These results indicate that the PHA-L promoter might be a useful tool in coffee for the seed-specific expression of genes related to coffee bean productivity, quality and pest protection. The biotechnological applicability of the α-AI1 gene for controlling CBB is also discussed. This work is the first report showing a seed-specific transgene expression in coffee plants.

Assessing the functionality and genetic diversity of lactococcal prophages.

PubMed

Kelleher, Philip; Mahony, Jennifer; Schweinlin, Katharina; Neve, Horst; Franz, Charles M; van Sinderen, Douwe

2018-05-02

Lactococcus lactis is a lactic acid bacterium that is intensively and globally exploited in commercial dairy food fermentations. Though the presence of prophages in lactococcal genomes is widely reported, only limited studies pertaining to the stability of prophages in lactococcal genomes have been performed. The current study reports on the complete genome exploration of thirty lactococcal strains for the presence of potentially intact prophages, so as to assess their genomic diversity and the associated risk or benefit of harbouring such prophages. Genomic predictions partnered with mitomycin C inductions and flow cytometric analysis of the induced cell lysates confirmed that only four strains consistently produced intact phage particles, thus indicating a relatively low risk associated with prophage induction in the fermentation setting. Our analysis revealed the widespread presence of putative phage-resistance systems encoded by lactococcal prophages, thus highlighting the potential benefits for host fitness. Many of the identified lactococcal prophages belong to the so-called P335 phage group, while a large group of phage remnants bear similarity to members of the 936 phage group. The P335 phage group was recently shown to encompass four distinct genetic lineages. Our study identified an additional lineage, thus expanding the diversity of this industrially significant phage group. Copyright © 2018 Elsevier B.V. All rights reserved.

The Unicellular Green Alga Chlamydomonas reinhardtii as an Experimental System to Study Chloroplast RNA Metabolism

NASA Astrophysics Data System (ADS)

Nickelsen, J.; Kück, U.

Chloroplasts are typical organelles of photoautotrophic eukaryotic cells which drive a variety of functions, including photosynthesis. For many years the unicellular green alga Chlamydomonas reinhardtii has served as an experimental organism for studying photosynthetic processes. The recent development of molecular tools for this organism together with efficient methods of genetic analysis and the availability of many photosynthesis mutants has now made this alga a powerful model system for the analysis of chloroplast biogenesis. For example, techniques have been developed to transfer recombinant DNA into both the nuclear and the chloroplast genome. This allows both complementation tests and analyses of gene functions in vivo. Moreover, site-specific DNA recombinations in the chloroplast allow targeted gene disruption experiments which enable a "reverse genetics" to be performed. The potential of the algal system for the study of chloroplast biogenesis is illustrated in this review by the description of regulatory systems of gene expression involved in organelle biogenesis. One example concerns the regulation of trans-splicing of chloroplast mRNAs, a process which is controlled by both multiple nuclear- and chloroplast-encoded factors. The second example involves the stabilization of chloroplast mRNAs. The available data lead us predict distinct RNA elements, which interact with trans-acting factors to protect the RNA against nucleolytic attacks.

Bioinformatics analysis to assess potential risks of allergenicity and toxicity of HRAP and PFLP proteins in genetically modified bananas resistant to Xanthomonas wilt disease.

PubMed

Jin, Yuan; Goodman, Richard E; Tetteh, Afua O; Lu, Mei; Tripathi, Leena

2017-11-01

Banana Xanthomonas wilt (BXW) disease threatens banana production and food security throughout East Africa. Natural resistance is lacking among common cultivars. Genetically modified (GM) bananas resistant to BXW disease were developed by inserting the hypersensitive response-assisting protein (Hrap) or/and the plant ferredoxin-like protein (Pflp) gene(s) from sweet pepper (Capsicum annuum). Several of these GM banana events showed 100% resistance to BXW disease under field conditions in Uganda. The current study evaluated the potential allergenicity and toxicity of the expressed proteins HRAP and PFLP based on evaluation of published information on the history of safe use of the natural source of the proteins as well as established bioinformatics sequence comparison methods to known allergens (www.AllergenOnline.org and NCBI Protein) and toxins (NCBI Protein). The results did not identify potential risks of allergy and toxicity to either HRAP or PFLP proteins expressed in the GM bananas that might suggest potential health risks to humans. We recognize that additional tests including stability of these proteins in pepsin assay, nutrient analysis and possibly an acute rodent toxicity assay may be required by national regulatory authorities. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Screening of mutations affecting protein stability and dynamics of FGFR1—A simulation analysis

PubMed Central

Doss, C. George Priya; Rajith, B.; Garwasis, Nimisha; Mathew, Pretty Raju; Raju, Anand Solomon; Apoorva, K.; William, Denise; Sadhana, N.R.; Himani, Tanwar; Dike, IP.

2012-01-01

Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 (FGFR1) destabilize protein and have been implicated in several genetic disorders like various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss syndrome, etc. In order to gain functional insight into mutation caused by amino acid substitution to protein function and expression, special emphasis was laid on molecular dynamics simulation techniques in combination with in silico tools such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68% nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT (37%), PolyPhen 2.0 (61%) and SNAP (58%). From the observed results, P722S mutation was found to be most deleterious by comparing results of all in silico tools. By molecular dynamics approach, we have shown that P722S mutation leads to increase in flexibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. In addition, biophysical analysis revealed a clear insight of stability loss due to P722S mutation in FGFR1 protein. Majority of mutations predicted by these in silico tools were in good concordance with the experimental results. PMID:27896051

Screening of mutations affecting protein stability and dynamics of FGFR1-A simulation analysis.

PubMed

Doss, C George Priya; Rajith, B; Garwasis, Nimisha; Mathew, Pretty Raju; Raju, Anand Solomon; Apoorva, K; William, Denise; Sadhana, N R; Himani, Tanwar; Dike, I P

2012-12-01

Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 ( FGFR1 ) destabilize protein and have been implicated in several genetic disorders like various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss syndrome, etc. In order to gain functional insight into mutation caused by amino acid substitution to protein function and expression, special emphasis was laid on molecular dynamics simulation techniques in combination with in silico tools such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68% nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT (37%), PolyPhen 2.0 (61%) and SNAP (58%). From the observed results, P722S mutation was found to be most deleterious by comparing results of all in silico tools. By molecular dynamics approach, we have shown that P722S mutation leads to increase in flexibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. In addition, biophysical analysis revealed a clear insight of stability loss due to P722S mutation in FGFR1 protein. Majority of mutations predicted by these in silico tools were in good concordance with the experimental results.

Suppressor Analysis of the Fusogenic Lambda Spanins.

PubMed

Cahill, Jesse; Rajaure, Manoj; Holt, Ashley; Moreland, Russell; O'Leary, Chandler; Kulkarni, Aneesha; Sloan, Jordan; Young, Ry

2017-07-15

The final step of lysis in phage λ infections of Escherichia coli is mediated by the spanins Rz and Rz1. These proteins form a complex that bridges the cell envelope and that has been proposed to cause fusion of the inner and outer membranes. Accordingly, mutations that block spanin function are found within coiled-coil domains and the proline-rich region, motifs essential in other fusion systems. To gain insight into spanin function, pseudorevertant alleles that restored plaque formation for lysis-defective mutants of Rz and Rz1 were selected. Most second-site suppressors clustered within a coiled-coil domain of Rz near the outer leaflet of the cytoplasmic membrane and were not allele specific. Suppressors largely encoded polar insertions within the hydrophobic core of the coiled-coil interface. Such suppressor changes resulted in decreased proteolytic stability of the Rz double mutants in vivo Unlike the wild type, in which lysis occurs while the cells retain a rod shape, revertant alleles with second-site suppressor mutations supported lysis events that were preceded by spherical cell formation. This suggests that destabilization of the membrane-proximal coiled coil restores function for defective spanin alleles by increasing the conformational freedom of the complex at the cost of its normal, all-or-nothing functionality. IMPORTANCE Caudovirales encode cell envelope-spanning proteins called spanins, which are thought to fuse the inner and outer membranes during phage lysis. Recent genetic analysis identified the functional domains of the lambda spanins, which are similar to class I viral fusion proteins. While the pre- and postfusion structures of model fusion systems have been well characterized, the intermediate structure(s) formed during the fusion reaction remains elusive. Genetic analysis would be expected to identify functional connections between intermediates. Since most membrane fusion systems are not genetically tractable, only few such investigations have been reported. Here, we report a suppressor analysis of lambda spanin function. To our knowledge this is the first suppression analysis of a class I-like complex and also the first such analysis of a prokaryote membrane fusion system. Copyright © 2017 American Society for Microbiology.

Rapid changes in genetic architecture of behavioural syndromes following colonization of a novel environment.

PubMed

Karlsson Green, K; Eroukhmanoff, F; Harris, S; Pettersson, L B; Svensson, E I

2016-01-01

Behavioural syndromes, that is correlated behaviours, may be a result from adaptive correlational selection, but in a new environmental setting, the trait correlation might act as an evolutionary constraint. However, knowledge about the quantitative genetic basis of behavioural syndromes, and the stability and evolvability of genetic correlations under different ecological conditions, is limited. We investigated the quantitative genetic basis of correlated behaviours in the freshwater isopod Asellus aquaticus. In some Swedish lakes, A. aquaticus has recently colonized a novel habitat and diverged into two ecotypes, presumably due to habitat-specific selection from predation. Using a common garden approach and animal model analyses, we estimated quantitative genetic parameters for behavioural traits and compared the genetic architecture between the ecotypes. We report that the genetic covariance structure of the behavioural traits has been altered in the novel ecotype, demonstrating divergence in behavioural correlations. Thus, our study confirms that genetic correlations behind behaviours can change rapidly in response to novel selective environments. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

The emergence of DNA in the RNA world: an in silico simulation study of genetic takeover.

PubMed

Ma, Wentao; Yu, Chunwu; Zhang, Wentao; Wu, Sanmao; Feng, Yu

2015-12-07

It is now popularly accepted that there was an "RNA world" in early evolution of life. This idea has a direct consequence that later on there should have been a takeover of genetic material - RNA by DNA. However, since genetic material carries genetic information, the "source code" of all living activities, it is actually reasonable to question the plausibility of such a "revolutionary" transition. Due to our inability to model relevant "primitive living systems" in reality, it is as yet impossible to explore the plausibility and mechanisms of the "genetic takeover" by experiments. Here we investigated this issue by computer simulation using a Monte-Carlo method. It shows that an RNA-by-DNA genetic takeover may be triggered by the emergence of a nucleotide reductase ribozyme with a moderate activity in a pure RNA system. The transition is unstable and limited in scale (i.e., cannot spread in the population), but can get strengthened and globalized if certain parameters are changed against RNA (i.e., in favor of DNA). In relation to the subsequent evolution, an advanced system with a larger genome, which uses DNA as genetic material and RNA as functional material, is modeled - the system cannot sustain if the nucleotide reductase ribozyme is "turned off" (thus, DNA cannot be synthesized). Moreover, the advanced system cannot sustain if only DNA's stability, template suitability or replication fidelity (any of the three) is turned down to the level of RNA's. Genetic takeover should be plausible. In the RNA world, such a takeover may have been triggered by the emergence of some ribozyme favoring the formation of deoxynucleotides. The transition may initially have been "weak", but could have been reinforced by environmental changes unfavorable to RNA (such as temperature or pH rise), and would have ultimately become irreversible accompanying the genome's enlargement. Several virtues of DNA (versus RNA) - higher stability against hydrolysis, greater suitability as template and higher fidelity in replication, should have, each in its own way, all been significant for the genetic takeover in evolution. This study enhances our understandings of the relationship between information and material in the living world.

A Case Study on Maximizing Aqua Feed Pellet Properties Using Response Surface Methodology and Genetic Algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tumuluru, Jaya

Aims: The present case study is on maximizing the aqua feed properties using response surface methodology and genetic algorithm. Study Design: Effect of extrusion process variables like screw speed, L/D ratio, barrel temperature, and feed moisture content were analyzed to maximize the aqua feed properties like water stability, true density, and expansion ratio. Place and Duration of Study: This study was carried out in the Department of Agricultural and Food Engineering, Indian Institute of Technology, Kharagpur, India. Methodology: A variable length single screw extruder was used in the study. The process variables selected were screw speed (rpm), length-to-diameter (L/D) ratio,more » barrel temperature (degrees C), and feed moisture content (%). The pelletized aqua feed was analyzed for physical properties like water stability (WS), true density (TD), and expansion ratio (ER). Extrusion experimental data was collected by based on central composite design. The experimental data was further analyzed using response surface methodology (RSM) and genetic algorithm (GA) for maximizing feed properties. Results: Regression equations developed for the experimental data has adequately described the effect of process variables on the physical properties with coefficient of determination values (R2) of > 0.95. RSM analysis indicated WS, ER, and TD were maximized at L/D ratio of 12-13, screw speed of 60-80 rpm, feed moisture content of 30-40%, and barrel temperature of = 80 degrees C for ER and TD and > 90 degrees C for WS. Based on GA analysis, a maxium WS of 98.10% was predicted at a screw speed of 96.71 rpm, L/D radio of 13.67, barrel temperature of 96.26 degrees C, and feed moisture content of 33.55%. Maximum ER and TD of 0.99 and 1346.9 kg/m3 was also predicted at screw speed of 60.37 and 90.24 rpm, L/D ratio of 12.18 and 13.52, barrel temperature of 68.50 and 64.88 degrees C, and medium feed moisture content of 33.61 and 38.36%. Conclusion: The present data analysis indicated that WS is mainly governed by barrel temperature and feed moisture content, which might have resulted in formation of starch-protein complexes due to denaturation of protein and gelatinization of starch. Screw speed coupled with temperature and feed moisture content controlled the ER and TD values. Higher screw speeds might have reduced the viscosity of the feed dough resulting in higher TD and lower ER values. Based on RSM and GA analysis screw speed, barrel temperature and feed moisture content were the interacting process variables influencing maximum WS followed by ER and TD.« less

Defying the activity-stability trade-off in enzymes: taking advantage of entropy to enhance activity and thermostability.

PubMed

Siddiqui, Khawar Sohail

2017-05-01

The biotechnological applications of enzymes are limited due to the activity-stability trade-off, which implies that an increase in activity is accompanied by a concomitant decrease in protein stability. This premise is based on thermally adapted homologous enzymes where cold-adapted enzymes show high intrinsic activity linked to enhanced thermolability. In contrast, thermophilic enzymes show low activity around ambient temperatures. Nevertheless, genetically and chemically modified enzymes are beginning to show that the activity-stability trade-off can be overcome. In this review, the origin of the activity-stability trade-off, the thermodynamic basis for enhanced activity and stability, and various approaches for escaping the activity-stability trade-off are discussed. The role of entropy in enhancing both the activity and the stability of enzymes is highlighted with a special emphasis placed on the involvement of solvent water molecules. This review is concluded with suggestions for further research, which underscores the implications of these findings in the context of productivity curves, the Daniel-Danson equilibrium model, catalytic antibodies, and life on cold planets.

Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo.

PubMed

Parisi, Federica; Riccardo, Sara; Daniel, Margaret; Saqcena, Mahesh; Kundu, Nandini; Pession, Annalisa; Grifoni, Daniela; Stocker, Hugo; Tabak, Esteban; Bellosta, Paola

2011-09-27

Genetic studies in Drosophila melanogaster reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR) pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways. Our biochemical studies show that insulin induces Myc protein accumulation in Drosophila S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3β ) a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3β activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia. Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in Drosophila. At the biochemical level we found that both these pathways converge at GSK3β to control Myc protein stability, while our genetic analysis shows that insulin and TOR pathways have different requirements for Myc activity during development of the eye, suggesting that Myc might be differentially induced by these pathways during growth or proliferation of cells that make up the ommatidia.

Genetic and environmental factors affecting cryptic variations in gene regulatory networks

PubMed Central

2013-01-01

Background Cryptic genetic variation (CGV) is considered to facilitate phenotypic evolution by producing visible variations in response to changes in the internal and/or external environment. Several mechanisms enabling the accumulation and release of CGVs have been proposed. In this study, we focused on gene regulatory networks (GRNs) as an important mechanism for producing CGVs, and examined how interactions between GRNs and the environment influence the number of CGVs by using individual-based simulations. Results Populations of GRNs were allowed to evolve under various stabilizing selections, and we then measured the number of genetic and phenotypic variations that had arisen. Our results showed that CGVs were not depleted irrespective of the strength of the stabilizing selection for each phenotype, whereas the visible fraction of genetic variation in a population decreased with increasing strength of selection. On the other hand, increasing the number of different environments that individuals encountered within their lifetime (i.e., entailing plastic responses to multiple environments) suppressed the accumulation of CGVs, whereas the GRNs with more genes and interactions were favored in such heterogeneous environments. Conclusions Given the findings that the number of CGVs in a population was largely determined by the size (order) of GRNs, we propose that expansion of GRNs and adaptation to novel environments are mutually facilitating and sustainable sources of evolvability and hence the origins of biological diversity and complexity. PMID:23622056

Genetic and environmental factors affecting cryptic variations in gene regulatory networks.

PubMed

Iwasaki, Watal M; Tsuda, Masaki E; Kawata, Masakado

2013-04-26

Cryptic genetic variation (CGV) is considered to facilitate phenotypic evolution by producing visible variations in response to changes in the internal and/or external environment. Several mechanisms enabling the accumulation and release of CGVs have been proposed. In this study, we focused on gene regulatory networks (GRNs) as an important mechanism for producing CGVs, and examined how interactions between GRNs and the environment influence the number of CGVs by using individual-based simulations. Populations of GRNs were allowed to evolve under various stabilizing selections, and we then measured the number of genetic and phenotypic variations that had arisen. Our results showed that CGVs were not depleted irrespective of the strength of the stabilizing selection for each phenotype, whereas the visible fraction of genetic variation in a population decreased with increasing strength of selection. On the other hand, increasing the number of different environments that individuals encountered within their lifetime (i.e., entailing plastic responses to multiple environments) suppressed the accumulation of CGVs, whereas the GRNs with more genes and interactions were favored in such heterogeneous environments. Given the findings that the number of CGVs in a population was largely determined by the size (order) of GRNs, we propose that expansion of GRNs and adaptation to novel environments are mutually facilitating and sustainable sources of evolvability and hence the origins of biological diversity and complexity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chubiz, Lon M.; Granger, Brian R.; Segre, Daniel

Conflict and cooperation between bacterial species drive the composition and function of microbial communities. Stability of these emergent properties will be influenced by the degree to which species' interactions are robust to genetic perturbations. We use genome-scale metabolic modeling to computationally analyze the impact of genetic changes when Escherichia coli and Salmonella enterica compete, or cooperate. We systematically knocked out in silico each reaction in the metabolic network of E. coli to construct all 2583 mutant stoichiometric models. Then, using a recently developed multi-scale computational framework, we simulated the growth of each mutant E. coli in the presence of S.more » enterica. The type of interaction between species was set by modulating the initial metabolites present in the environment. We found that the community was most robust to genetic perturbations when the organisms were cooperating. Species ratios were more stable in the cooperative community, and community biomass had equal variance in the two contexts. Additionally, the number of mutations that have a substantial effect is lower when the species cooperate than when they are competing. In contrast, when mutations were added to the S. enterica network the system was more robust when the bacteria were competing. These results highlight the utility of connecting metabolic mechanisms and studies of ecological stability. Cooperation and conflict alter the connection between genetic changes and properties that emerge at higher levels of biological organization.« less

Community specificity: life and afterlife effects of genes.

PubMed

Whitham, Thomas G; Gehring, Catherine A; Lamit, Louis J; Wojtowicz, Todd; Evans, Luke M; Keith, Arthur R; Smith, David Solance

2012-05-01

Community-level genetic specificity results when individual genotypes or populations of the same species support different communities. Our review of the literature shows that genetic specificity exhibits both life and afterlife effects; it is a widespread phenomenon occurring in diverse taxonomic groups, aquatic to terrestrial ecosystems, and species-poor to species-rich systems. Such specificity affects species interactions, evolution, ecosystem processes and leads to community feedbacks on the performance of the individuals expressing the traits. Thus, genetic specificity by communities appears to be fundamentally important, suggesting that specificity is a major driver of the biodiversity and stability of the world's ecosystems. Copyright © 2012. Published by Elsevier Ltd.

The Stochastic Evolutionary Game for a Population of Biological Networks Under Natural Selection

PubMed Central

Chen, Bor-Sen; Ho, Shih-Ju

2014-01-01

In this study, a population of evolutionary biological networks is described by a stochastic dynamic system with intrinsic random parameter fluctuations due to genetic variations and external disturbances caused by environmental changes in the evolutionary process. Since information on environmental changes is unavailable and their occurrence is unpredictable, they can be considered as a game player with the potential to destroy phenotypic stability. The biological network needs to develop an evolutionary strategy to improve phenotypic stability as much as possible, so it can be considered as another game player in the evolutionary process, ie, a stochastic Nash game of minimizing the maximum network evolution level caused by the worst environmental disturbances. Based on the nonlinear stochastic evolutionary game strategy, we find that some genetic variations can be used in natural selection to construct negative feedback loops, efficiently improving network robustness. This provides larger genetic robustness as a buffer against neutral genetic variations, as well as larger environmental robustness to resist environmental disturbances and maintain a network phenotypic traits in the evolutionary process. In this situation, the robust phenotypic traits of stochastic biological networks can be more frequently selected by natural selection in evolution. However, if the harbored neutral genetic variations are accumulated to a sufficiently large degree, and environmental disturbances are strong enough that the network robustness can no longer confer enough genetic robustness and environmental robustness, then the phenotype robustness might break down. In this case, a network phenotypic trait may be pushed from one equilibrium point to another, changing the phenotypic trait and starting a new phase of network evolution through the hidden neutral genetic variations harbored in network robustness by adaptive evolution. Further, the proposed evolutionary game is extended to an n-tuple evolutionary game of stochastic biological networks with m players (competitive populations) and k environmental dynamics. PMID:24558296

Long term impacts of CMC/nZVI amendment injection on organohalide-respiring microbial communities at a chlorinated solvent field site

NASA Astrophysics Data System (ADS)

Kocur, C. M.; Lomheim, L.; Boparai, H. K.; Chowdhury, A. I.; Weber, K.; Austrins, L. M.; Sleep, B.; O'Carroll, D. M.; Edwards, E.

2014-12-01

Injection of carboxymethyl-cellulose stabilized nanoscale Zero Valent Iron (CMC/nZVI) has received significant attention in the last decade as an emerging alternative for in-situ remediation of chlorinated solvents and other recalcitrant compounds. There has also been some indication that injection of nZVI will create conditions that will stimulate in-situ microbial populations, leading to further contaminant degradation. Carboxy-methyl cellulose (CMC) is commonly used for nZVI synthesis as it provides steric stabilization for the nanoparticles, however, the CMC is equally important as a subsurface amendment as it may act as a fermentable substrate for microorganisms in-situ. In this study, microbial communities were monitored over a 2.5 year period following the injection of CMC/nZVI at a chlorinated solvent remediation site. Dehalococcoides spp. genetic markers and vinyl chloride reductase genes (vcrA) were targeted in the 16s RNA using quantitative polymerase chain reaction (qPCR). This analysis was complimented with a suite of aqueous chlorinated ethene, ethane, and methane compounds to monitor degradation. Following the injection of CMC/nZVI a decline of parent chlorinated compound concentrations was observed as well as the emergence of daughter products. A period of abiotic nZVI oxidation is believed to be responsible for a portion of the degradation at the site, however, a prolonged period of contaminant degradation followed and is believed to be the result of organohalide-respiring microorganisms native to the site. Further analysis was performed on the microbial samples using 454 pyrotag sequencing of amplified 16S rRNA genes to obtain the genetic profile of the microbial community. Of particular interest within this large genomic profile is the characterization of the stable population of important organohalide-respiring microorganisms on site. Results suggest that there is a distinctly different response in the organohalide-respiring microbial community in areas of the site where CMC/nZVI amendments were injected compared to a background response.

Meta-analyses of microarrays of Arabidopsis asymmetric leaves1 (as1), as2 and their modifying mutants reveal a critical role for the ETT pathway in stabilization of adaxial-abaxial patterning and cell division during leaf development.

PubMed

Takahashi, Hiro; Iwakawa, Hidekazu; Ishibashi, Nanako; Kojima, Shoko; Matsumura, Yoko; Prananingrum, Pratiwi; Iwasaki, Mayumi; Takahashi, Anna; Ikezaki, Masaya; Luo, Lilan; Kobayashi, Takeshi; Machida, Yasunori; Machida, Chiyoko

2013-03-01

It is necessary to use algorithms to analyze gene expression data from DNA microarrays, such as in clustering and machine learning. Previously, we developed the knowledge-based fuzzy adaptive resonance theory (KB-FuzzyART), a clustering algorithm suitable for analyzing gene expression data, to find clues for identifying gene networks. Leaf primordia form around the shoot apical meristem (SAM), which consists of indeterminate stem cells. Upon initiation of leaf development, adaxial-abaxial patterning is crucial for lateral expansion, via cellular proliferation, and the formation of flat symmetric leaves. Many regulatory genes that specify such patterning have been identified. Analysis by the KB-FuzzyART and subsequent molecular and genetic analyses previously showed that ASYMMETRIC LEAVES1 (AS1) and AS2 repress the expression of some abaxial-determinant genes, such as AUXIN RESPONSE FACTOR3 (ARF3)/ETTIN (ETT) and ARF4, which are responsible for defects in leaf adaxial-abaxial polarity in as1 and as2. In the present study, genetic analysis revealed that ARF3/ETT and ARF4 were regulated by modifier genes, BOBBER1 (BOB1) and ELONGATA3 (ELO3), together with AS1-AS2. We analyzed expression arrays with as2 elo3 and as2 bob1, and extracted genes downstream of ARF3/ETT by using KB-FuzzyART and molecular analyses. The results showed that expression of Kip-related protein (KRP) (for inhibitors of cyclin-dependent protein kinases) and Isopentenyltransferase (IPT) (for biosynthesis of cytokinin) genes were controlled by AS1-AS2 through ARF3/ETT and ARF4 functions, which suggests that the AS1-AS2-ETT pathway plays a critical role in controlling the cell division cycle and the biosynthesis of cytokinin around SAM to stabilize leaf development in Arabidopsis thaliana.

The Acquisition of Indigenous Plasmids by a Genetically Marked Pseudomonad Population Colonizing the Sugar Beet Phytosphere Is Related to Local Environmental Conditions

PubMed Central

Lilley, A. K.; Bailey, M. J.

1997-01-01

The transfer of naturally occurring conjugative plasmids from the indigenous microflora to a genetically modified population of bacteria colonizing the phytospheres of plants has been observed. The marked strain (Pseudomonas fluorescens SBW25EeZY6KX) was introduced as a seed dressing to sugar beets (Beta vulgaris var. Amethyst) as part of a field experiment to assess the ecology and genetic stability of deliberately released bacterial inocula. The sustained populations of the introduced strain, which colonized the phytosphere, were assessed throughout the growing season for the acquisition of plasmids conferring mercury resistance (Hg(supr)). Transconjugants were isolated only from root and leaf samples collected within a narrow temporal window coincident with the midseason maturation of the crop. Conjugal-transfer events were recorded during this defined period in two separate field release experiments conducted over consecutive years. On one occasion seven of nine individual plants sampled supported transconjugant P. fluorescens SBW25EeZY6KX, demonstrating that conjugative gene transfer between bacterial populations in the phytosphere may be a common event under specific environmental conditions. The plasmids acquired in situ by the colonizing inocula were identified as natural variants of restriction digest pattern group I, III, or IV plasmids from five genetically distinct groups of large, conjugative mercury resistance plasmids known to persist in the phytospheres of sugar beets at the field site. These data demonstrate not only that gene transfer may be a common event but also that the genetic and phenotypic stability of inocula released into the natural environment cannot be predicted. PMID:16535580

Spatial and temporal variability of microgeographic genetic structure in white-tailed deer

USGS Publications Warehouse

Scribner, Kim T.; Smith, Michael H.; Chesser, Ronald K.

1997-01-01

Techniques are described that define contiguous genetic subpopulations of white-tailed deer (Odocoileus virginianus) based on the spatial dispersion of 4,749 individuals that possessed discrete character values (alleles or genotypes) during each of 6 years (1974-1979). White-tailed deer were not uniformly distributed in space, but exhibited considerable spatial genetic structuring. Significant non-random clusters of individuals were documented during each year based on specific alleles and genotypes at the Sdh locus. Considerable temporal variation was observed in the position and genetic composition of specific clusters, which reflected changes in allele frequency in small geographic areas. The position of clusters did not consistently correspond with traditional management boundaries based on major discontinuities in habitat (swamp versus upland) and hunt compartments that were defined by roads and streams. Spatio-temporal stability of observed genetic contiguous clusters was interpreted relative to method and intensity of harvest, movements, and breeding ecology.

Genetic Variation in DNA Repair Genes and Prostate Cancer Risk: Results from a Population-Based Study

PubMed Central

Agalliu, Ilir; Kwon, Erika M; Salinas, Claudia A.; Koopmeiners, Joseph S.; Ostrander, Elaine A.; Stanford, Janet L.

2009-01-01

Objective DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease of DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk. Methods Pooled data from two population-based studies (1,457 cases and 1,351 controls) were analyzed to examine associations between 28 SNPs in 9 DNA repair genes (APEX1, BRCA2, ERCC2, ERCC4, MGMT, MUTYH, OGG1, XPC, and XRCC1) and prostate cancer risk. We also explored whether associations varied by smoking, by family history or clinical features of prostate cancer. Results There were no associations between these SNPs and overall risk of prostate cancer. Risks did not vary either by smoking or by family history of prostate cancer. Although, two SNPs in BRCA2 (rs144848, rs1801406) and two SNPs in ERCC2 (rs1799793, rs13181) showed stronger associations with high Gleason score or advanced stage tumors when comparing homozygous men carrying the minor vs. major allele, results were not statistically significantly different between clinically aggressive and non-aggressive tumors. Conclusion Overall this study found no associations between prostate cancer and the SNPs in DNA repair genes. Given the complexity of this pathway and its crucial role in maintenance of genomic stability a pathway-based analysis of all 150 genes in DNA repair pathways, as well as exploration of gene-environment interactions may be warranted. PMID:19902366

Development and use of molecular markers: past and present.

PubMed

Grover, Atul; Sharma, P C

2016-01-01

Molecular markers, due to their stability, cost-effectiveness and ease of use provide an immensely popular tool for a variety of applications including genome mapping, gene tagging, genetic diversity diversity, phylogenetic analysis and forensic investigations. In the last three decades, a number of molecular marker techniques have been developed and exploited worldwide in different systems. However, only a handful of these techniques, namely RFLPs, RAPDs, AFLPs, ISSRs, SSRs and SNPs have received global acceptance. A recent revolution in DNA sequencing techniques has taken the discovery and application of molecular markers to high-throughput and ultrahigh-throughput levels. Although, the choice of marker will obviously depend on the targeted use, microsatellites, SNPs and genotyping by sequencing (GBS) largely fulfill most of the user requirements. Further, modern transcriptomic and functional markers will lead the ventures onto high-density genetic map construction, identification of QTLs, breeding and conservation strategies in times to come in combination with other high throughput techniques. This review presents an overview of different marker technologies and their variants with a comparative account of their characteristic features and applications.

Quantitative proteomic analysis of human breast epithelial cells with differential telomere length

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Li-Rong; Chan, King C.; Tahara, Hidetoshi

Telomeres play important functional roles in cell proliferation, cell cycle regulation, and genetic stability, in which telomere length is critical. In this study, quantitative proteome comparisons for the human breast epithelial cells with short and long telomeres (184-hTERT{sub L} vs. 184-hTERT{sub S} and 90P-hTERT{sub L} vs. 90P-hTERT{sub S}), resulting from transfection of the human telomerase reverse transcriptase (hTERT) gene, were performed using cleavable isotope-coded affinity tags. More than 2000 proteins were quantified in each comparative experiment, with approximately 77% of the proteins identified in both analyses. In the cells with long telomeres, significant and consistent alterations were observed in metabolismmore » (amino acid, nucleotide, and lipid metabolism), genetic information transmission (transcription and translation regulation, spliceosome and ribosome complexes), and cell signaling. Interestingly, the DNA excision repair pathway is enhanced, while integrin and its ligands are downregulated in the cells with long telomeres. These results may provide valuable information related to telomere functions.« less

Temporal genetic stability of Stegomyia aegypti (= Aedes aegypti) populations.

PubMed

Gloria-Soria, A; Kellner, D A; Brown, J E; Gonzalez-Acosta, C; Kamgang, B; Lutwama, J; Powell, J R

2016-06-01

The mosquito Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) is the primary vector of viruses that cause yellow fever, dengue and Chikungunya fever. In the absence of effective vaccines, the reduction of these diseases relies on vector control strategies. The success of these strategies is tightly linked to the population dynamics of target populations. In the present study, 14 collections from St. aegypti populations separated by periods of 1-13 years were analysed to determine their temporal genetic stability. Although temporal structure is discernible in most populations, the degree of temporal differentiation is dependent on the population and does not obscure the geographic structure of the various populations. The results suggest that performing detailed studies in the years prior to and after population reduction- or modification-based control interventions at each target field site may be useful in assessing the probability of success. © 2016 The Royal Entomological Society.

DRIFTSEL: an R package for detecting signals of natural selection in quantitative traits.

PubMed

Karhunen, M; Merilä, J; Leinonen, T; Cano, J M; Ovaskainen, O

2013-07-01

Approaches and tools to differentiate between natural selection and genetic drift as causes of population differentiation are of frequent demand in evolutionary biology. Based on the approach of Ovaskainen et al. (2011), we have developed an R package (DRIFTSEL) that can be used to differentiate between stabilizing selection, diversifying selection and random genetic drift as causes of population differentiation in quantitative traits when neutral marker and quantitative genetic data are available. Apart from illustrating the use of this method and the interpretation of results using simulated data, we apply the package on data from three-spined sticklebacks (Gasterosteus aculeatus) to highlight its virtues. DRIFTSEL can also be used to perform usual quantitative genetic analyses in common-garden study designs. © 2013 John Wiley & Sons Ltd.

Alanine Scanning Mutagenesis Identifies an Asparagine–Arginine–Lysine Triad Essential to Assembly of the Shell of the Pdu Microcompartment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinha, Sharmistha; Cheng, Shouqiang; Sung, Yea Won

2014-06-01

Bacterial microcompartments (MCPs) are the simplest organelles known. They function to enhance metabolic pathways by confining several related enzymes inside an all-protein envelope called the shell. In this study, we investigated the factors that govern MCP assembly by performing scanning mutagenesis on the surface residues of PduA, a major shell protein of the MCP used for 1,2-propanediol degradation. Biochemical, genetic, and structural analysis of 20 mutants allowed us to determine that PduA K26, N29, and R79 are crucial residues that stabilize the shell of the 1,2-propanediol MCP. In addition, we identify two PduA mutants (K37A and K55A) that impair MCPmore » function most likely by altering the permeability of its protein shell. These are the first studies to examine the phenotypic effects of shell protein structural mutations in an MCP system. The findings reported here may be applicable to engineering protein containers with improved stability for biotechnology applications.« less

Telomere healing following DNA polymerase arrest-induced breakages is likely the main mechanism generating chromosome 4p terminal deletions.

PubMed

Hannes, Femke; Van Houdt, Jeroen; Quarrell, Oliver W; Poot, Martin; Hochstenbach, Ron; Fryns, Jean-Pierre; Vermeesch, Joris R

2010-12-01

Constitutional developmental disorders are frequently caused by terminal chromosomal deletions. The mechanisms and/or architectural features that might underlie those chromosome breakages remain largely unexplored. Because telomeres are the vital DNA protein complexes stabilizing linear chromosomes against chromosome degradation, fusion, and incomplete replication, those terminal-deleted chromosomes acquired new telomeres either by telomere healing or by telomere capture. To unravel the mechanisms leading to chromosomal breakage and healing, we sequenced nine chromosome 4p terminal deletion boundaries. A computational analysis of the breakpoint flanking region, including 12 previously published pure terminal breakage sites, was performed in order to identify architectural features that might be involved in this process. All terminal 4p truncations were likely stabilized by telomerase-mediated telomere healing. In the majority of breakpoints multiple genetic elements have a potential to induce secondary structures and an enrichment in replication stalling site motifs were identified. These findings suggest DNA replication stalling-induced chromosome breakage during early development is the first mechanistic step leading toward terminal deletion syndromes. © 2010 Wiley-Liss, Inc.

Differential regulation of polarized synaptic vesicle trafficking and synapse stability in neural circuit rewiring in Caenorhabditis elegans

PubMed Central

Kurup, Naina; Kono, Karina

2017-01-01

Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation. Here, we further investigate cellular control of circuit rewiring through the analysis of mutants obtained in a forward genetic screen. Using live imaging, we characterize novel mutations that alter cargo binding in the dynein motor complex and enhance anterograde synaptic vesicle movement during remodeling, providing in vivo evidence for the tug-of-war between kinesin and dynein in fast axonal transport. We also find that a casein kinase homolog, TTBK-3, inhibits stabilization of nascent synapses in their new locations, a previously unexplored facet of structural plasticity of synapses. Our study delineates temporally distinct signaling pathways that are required for effective neural circuit refinement. PMID:28636662

Understanding the Evolution and Stability of the G-Matrix

PubMed Central

Arnold, Stevan J.; Bürger, Reinhard; Hohenlohe, Paul A.; Ajie, Beverley C.; Jones, Adam G.

2011-01-01

The G-matrix summarizes the inheritance of multiple, phenotypic traits. The stability and evolution of this matrix are important issues because they affect our ability to predict how the phenotypic traits evolve by selection and drift. Despite the centrality of these issues, comparative, experimental, and analytical approaches to understanding the stability and evolution of the G-matrix have met with limited success. Nevertheless, empirical studies often find that certain structural features of the matrix are remarkably constant, suggesting that persistent selection regimes or other factors promote stability. On the theoretical side, no one has been able to derive equations that would relate stability of the G-matrix to selection regimes, population size, migration, or to the details of genetic architecture. Recent simulation studies of evolving G-matrices offer solutions to some of these problems, as well as a deeper, synthetic understanding of both the G-matrix and adaptive radiations. PMID:18973631

Temporal stability of parasite distribution and genetic variability values of Contracaecum osculatum sp. D and C. osculatum sp. E (Nematoda: Anisakidae) from fish of the Ross Sea (Antarctica)

PubMed Central

Mattiucci, Simonetta; Cipriani, Paolo; Paoletti, Michela; Nardi, Valentina; Santoro, Mario; Bellisario, Bruno; Nascetti, Giuseppe

2015-01-01

The Ross Sea, Eastern Antarctica, is considered a “pristine ecosystem” and a biodiversity “hotspot” scarcely impacted by humans. The sibling species Contracaecum osculatum sp. D and C. osculatum sp. E are anisakid parasites embedded in the natural Antarctic marine ecosystem. Aims of this study were to: identify the larvae of C. osculatum (s.l.) recovered in fish hosts during the XXVII Italian Expedition to Antarctica (2011–2012); perform a comparative analysis of the contemporary parasitic load and genetic variability estimates of C. osculatum sp. D and C. osculatum sp. E with respect to samples collected during the expedition of 1993–1994; to provide ecological data on these parasites. 200 fish specimens (Chionodraco hamatus, Trematomus bernacchii, Trematomus hansoni, Trematomus newnesi) were analysed for Contracaecum sp. larvae, identified at species level by allozyme diagnostic markers and sequences analysis of the mtDNA cox2 gene. Statistically significant differences were found between the occurrence of C. osculatum sp. D and C. osculatum sp. E in different fish species. C. osculatum sp. E was more prevalent in T. bernacchii; while, a higher percentage of C. osculatum sp. D occurred in Ch. hamatus and T. hansoni. The two species also showed differences in the host infection site: C. osculatum sp. D showed higher percentage of infection in the fish liver. High genetic variability values at both nuclear and mitochondrial level were found in the two species in both sampling periods. The parasitic infection levels by C. osculatum sp. D and sp. E and their estimates of genetic variability showed no statistically significant variation over a temporal scale (2012 versus 1994). This suggests that the low habitat disturbance of the Antarctic region permits the maintenance of stable ecosystem trophic webs, which contributes to the maintenance of a large populations of anisakid nematodes with high genetic variability. PMID:26767164

INTEGRATING GENETIC AND STRUCTURAL DATA ON HUMAN PROTEIN KINOME IN NETWORK-BASED MODELING OF KINASE SENSITIVITIES AND RESISTANCE TO TARGETED AND PERSONALIZED ANTICANCER DRUGS.

PubMed

Verkhivker, Gennady M

2016-01-01

The human protein kinome presents one of the largest protein families that orchestrate functional processes in complex cellular networks, and when perturbed, can cause various cancers. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Coupled with the evolution of system biology approaches, genomic and proteomic technologies are rapidly identifying and charactering novel resistance mechanisms with the goal to inform rationale design of personalized kinase drugs. Integration of experimental and computational approaches can help to bring these data into a unified conceptual framework and develop robust models for predicting the clinical drug resistance. In the current study, we employ a battery of synergistic computational approaches that integrate genetic, evolutionary, biochemical, and structural data to characterize the effect of cancer mutations in protein kinases. We provide a detailed structural classification and analysis of genetic signatures associated with oncogenic mutations. By integrating genetic and structural data, we employ network modeling to dissect mechanisms of kinase drug sensitivities to oncogenic EGFR mutations. Using biophysical simulations and analysis of protein structure networks, we show that conformational-specific drug binding of Lapatinib may elicit resistant mutations in the EGFR kinase that are linked with the ligand-mediated changes in the residue interaction networks and global network properties of key residues that are responsible for structural stability of specific functional states. A strong network dependency on high centrality residues in the conformation-specific Lapatinib-EGFR complex may explain vulnerability of drug binding to a broad spectrum of mutations and the emergence of drug resistance. Our study offers a systems-based perspective on drug design by unravelling complex relationships between robustness of targeted kinase genes and binding specificity of targeted kinase drugs. We discuss how these approaches can exploit advances in chemical biology and network science to develop novel strategies for rationally tailored and robust personalized drug therapies.

A Common Suite of Coagulation Proteins Function in Drosophila Muscle Attachment.

PubMed

Green, Nicole; Odell, Nadia; Zych, Molly; Clark, Cheryl; Wang, Zong-Heng; Biersmith, Bridget; Bajzek, Clara; Cook, Kevin R; Dushay, Mitchell S; Geisbrecht, Erika R

2016-11-01

The organization and stability of higher order structures that form in the extracellular matrix (ECM) to mediate the attachment of muscles are poorly understood. We have made the surprising discovery that a subset of clotting factor proteins are also essential for muscle attachment in the model organism Drosophila melanogaster One such coagulation protein, Fondue (Fon), was identified as a novel muscle mutant in a pupal lethal genetic screen. Fon accumulates at muscle attachment sites and removal of this protein results in decreased locomotor behavior and detached larval muscles. A sensitized genetic background assay reveals that fon functions with the known muscle attachment genes Thrombospondin (Tsp) and Tiggrin (Tig). Interestingly, Tig is also a component of the hemolymph clot. We further demonstrate that an additional clotting protein, Larval serum protein 1γ (Lsp1γ), is also required for muscle attachment stability and accumulates where muscles attach to tendons. While the local biomechanical and organizational properties of the ECM vary greatly depending on the tissue microenvironment, we propose that shared extracellular protein-protein interactions influence the strength and elasticity of ECM proteins in both coagulation and muscle attachment. Copyright © 2016 by the Genetics Society of America.

Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

PubMed

Johnson, Norman A; Porter, Adam H

2007-01-01

Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

Some like it hot, some like it cold: Temperature dependent biotechnological applications and improvements in extremophilic enzymes.

PubMed

Siddiqui, Khawar Sohail

2015-12-01

The full biotechnological exploitation of enzymes is still hampered by their low activity, low stability and high cost. Temperature-dependent catalytic properties of enzymes are a key to efficient and cost-effective translation to commercial applications. Organisms adapted to temperature extremes are a rich source of enzymes with broad ranging thermal properties which, if isolated, characterized and their structure-function-stability relationship elucidated, could underpin a variety of technologies. Enzymes from thermally-adapted organisms such as psychrophiles (low-temperature) and thermophiles (high-temperature) are a vast natural resource that is already under scrutiny for their biotechnological potential. However, psychrophilic and thermophilic enzymes show an activity-stability trade-off that necessitates the use of various genetic and chemical modifications to further improve their properties to suit various industrial applications. This review describes in detail the properties and biotechnological applications of both cold-adapted and thermophilic enzymes. Furthermore, the review critically examines ways to improve their value for biotechnology, concluding by proposing an integrated approach involving thermally-adapted, genetically and magnetically modified enzymes to make biocatalysis more efficient and cost-effective. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic characterization of the non-structural protein-3 gene of bluetongue virus serotype-2 isolate from India.

PubMed

Pudupakam, Raghavendra Sumanth; Raghunath, Shobana; Pudupakam, Meghanath; Daggupati, Sreenivasulu

2017-03-01

Sequence analysis and phylogenetic studies based on non-structural protein-3 (NS3) gene are important in understanding the evolution and epidemiology of bluetongue virus (BTV). This study was aimed at characterizing the NS3 gene sequence of Indian BTV serotype-2 (BTV2) to elucidate its genetic relationship to global BTV isolates. The NS3 gene of BTV2 was amplified from infected BHK-21 cell cultures, cloned and subjected to sequence analysis. The generated NS3 gene sequence was compared with the corresponding sequences of different BTV serotypes across the world, and a phylogenetic relationship was established. The NS3 gene of BTV2 showed moderate levels of variability in comparison to different BTV serotypes, with nucleotide sequence identities ranging from 81% to 98%. The region showed high sequence homology of 93-99% at amino acid level with various BTV serotypes. The PPXY/PTAP late domain motifs, glycosylation sites, hydrophobic domains, and the amino acid residues critical for virus-host interactions were conserved in NS3 protein. Phylogenetic analysis revealed that BTV isolates segregate into four topotypes and that the Indian BTV2 in subclade IA is closely related to Asian and Australian origin strains. Analysis of the NS3 gene indicated that Indian BTV2 isolate is closely related to strains from Asia and Australia, suggesting a common origin of infection. Although the pattern of evolution of BTV2 isolate is different from other global isolates, the deduced amino acid sequence of NS3 protein demonstrated high molecular stability.

Genetic characterization of the non-structural protein-3 gene of bluetongue virus serotype-2 isolate from India

PubMed Central

Pudupakam, Raghavendra Sumanth; Raghunath, Shobana; Pudupakam, Meghanath; Daggupati, Sreenivasulu

2017-01-01

Aim: Sequence analysis and phylogenetic studies based on non-structural protein-3 (NS3) gene are important in understanding the evolution and epidemiology of bluetongue virus (BTV). This study was aimed at characterizing the NS3 gene sequence of Indian BTV serotype-2 (BTV2) to elucidate its genetic relationship to global BTV isolates. Materials and Methods: The NS3 gene of BTV2 was amplified from infected BHK-21 cell cultures, cloned and subjected to sequence analysis. The generated NS3 gene sequence was compared with the corresponding sequences of different BTV serotypes across the world, and a phylogenetic relationship was established. Results: The NS3 gene of BTV2 showed moderate levels of variability in comparison to different BTV serotypes, with nucleotide sequence identities ranging from 81% to 98%. The region showed high sequence homology of 93-99% at amino acid level with various BTV serotypes. The PPXY/PTAP late domain motifs, glycosylation sites, hydrophobic domains, and the amino acid residues critical for virus-host interactions were conserved in NS3 protein. Phylogenetic analysis revealed that BTV isolates segregate into four topotypes and that the Indian BTV2 in subclade IA is closely related to Asian and Australian origin strains. Conclusion: Analysis of the NS3 gene indicated that Indian BTV2 isolate is closely related to strains from Asia and Australia, suggesting a common origin of infection. Although the pattern of evolution of BTV2 isolate is different from other global isolates, the deduced amino acid sequence of NS3 protein demonstrated high molecular stability. PMID:28435199

Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus

PubMed Central

Hughes, Joseph; Biek, Roman; Litster, Annette; Willett, Brian J.; Hosie, Margaret J.

2015-01-01

Analysing the evolution of feline immunodeficiency virus (FIV) at the intra-host level is important in order to address whether the diversity and composition of viral quasispecies affect disease progression. We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at a rate of 1.16×10−3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3–V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3–V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation. Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximum evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared with human immunodeficiency virus might explain why many naturally infected cats do not progress rapidly to AIDS. PMID:25535323

Economic evaluation of Cardio inCode®, a clinical-genetic function for coronary heart disease risk assessment.

PubMed

Ramírez de Arellano, A; Coca, A; de la Figuera, M; Rubio-Terrés, C; Rubio-Rodríguez, D; Gracia, A; Boldeanu, A; Puig-Gilberte, J; Salas, E

2013-10-01

A clinical–genetic function (Cardio inCode®) was generated using genetic variants associated with coronary heart disease (CHD), but not with classical CHD risk factors, to achieve a more precise estimation of the CHD risk of individuals by incorporating genetics into risk equations [Framingham and REGICOR (Registre Gironí del Cor)]. The objective of this study was to conduct an economic analysis of the CHD risk assessment with Cardio inCode®, which incorporates the patient’s genetic risk into the functions of REGICOR and Framingham, compared with the standard method (using only the functions). A Markov model was developed with seven states of health (low CHD risk, moderate CHD risk, high CHD risk, CHD event, recurrent CHD, chronic CHD, and death). The reclassification of CHD risk derived from genetic information and transition probabilities between states was obtained from a validation study conducted in cohorts of REGICOR (Spain) and Framingham (USA). It was assumed that patients classified as at moderate risk by the standard method were the best candidates to test the risk reclassification with Cardio inCode®. The utilities and costs (€; year 2011 values) of Markov states were obtained from the literature and Spanish sources. The analysis was performed from the perspective of the Spanish National Health System, for a life expectancy of 82 years in Spain. An annual discount rate of 3.5 % for costs and benefits was applied. For a Cardio inCode® price of €400, the cost per QALY gained compared with the standard method [incremental cost-effectiveness ratio (ICER)] would be €12,969 and €21,385 in REGICOR and Framingham cohorts, respectively. The threshold price of Cardio inCode® to reach the ICER threshold generally accepted in Spain (€30,000/QALY) would range between €668 and €836. The greatest benefit occurred in the subgroup of patients with moderate–high risk, with a high-risk reclassification of 22.8 % and 12 % of patients and an ICER of €1,652/QALY and €5,884/QALY in the REGICOR and Framingham cohorts, respectively. Sensitivity analyses confirmed the stability of the study results. Cardio inCode® is a cost-effective risk score option in CHD risk assessment compared with the standard method.

Genetic Architecture Promotes the Evolution and Maintenance of Cooperation

PubMed Central

Frénoy, Antoine; Taddei, François; Misevic, Dusan

2013-01-01

When cooperation has a direct cost and an indirect benefit, a selfish behavior is more likely to be selected for than an altruistic one. Kin and group selection do provide evolutionary explanations for the stability of cooperation in nature, but we still lack the full understanding of the genomic mechanisms that can prevent cheater invasion. In our study we used Aevol, an agent-based, in silico genomic platform to evolve populations of digital organisms that compete, reproduce, and cooperate by secreting a public good for tens of thousands of generations. We found that cooperating individuals may share a phenotype, defined as the amount of public good produced, but have very different abilities to resist cheater invasion. To understand the underlying genetic differences between cooperator types, we performed bio-inspired genomics analyses of our digital organisms by recording and comparing the locations of metabolic and secretion genes, as well as the relevant promoters and terminators. Association between metabolic and secretion genes (promoter sharing, overlap via frame shift or sense-antisense encoding) was characteristic for populations with robust cooperation and was more likely to evolve when secretion was costly. In mutational analysis experiments, we demonstrated the potential evolutionary consequences of the genetic association by performing a large number of mutations and measuring their phenotypic and fitness effects. The non-cooperating mutants arising from the individuals with genetic association were more likely to have metabolic deleterious mutations that eventually lead to selection eliminating such mutants from the population due to the accompanying fitness decrease. Effectively, cooperation evolved to be protected and robust to mutations through entangled genetic architecture. Our results confirm the importance of second-order selection on evolutionary outcomes, uncover an important genetic mechanism for the evolution and maintenance of cooperation, and suggest promising methods for preventing gene loss in synthetically engineered organisms. PMID:24278000

Association of FcεRIβ polymorphisms with risk of asthma and allergic rhinitis: Evidence based on 29 case-control studies.

PubMed

Guo, Huanhuan; Peng, Tao; Luo, Ping; Li, Huabin; Huang, Shuo; Li, Shuang; Zhao, Weidong; Zhou, Xuhong

2018-04-13

Purpose: Accumulating evidence has shown that allergic diseases are caused by a complex interaction of genetic and environmental factors, some single nucleotide polymorphisms (SNPs) existing in high-affinity IgE receptor β chain (FcεRIβ) are potential risk factors for allergic diseases. However, the results have been inconsistent and inconclusive due to the limited statistical power in individual study. Thus, we conducted a meta-analysis to systematically evaluate the association between FcεRIβ SNPs and allergic diseases risk. Methods: Eligible studies were collected from PubMed, Embase, Web of Science, CNKI, and WanFang databases. Pooled odd ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated to assess the strength of the relationships between five polymorphisms (E237G, -109 C/T, RsaI_in2, RsaI_ex7 and I181L) and the risk of allergic diseases by using five genetic models. In addition, the stability of our analysis was evaluated by publication bias, sensitivity and heterogeneity analysis. Results: Overall, a total of 29 case-control studies were included in this meta-analysis. We found that E237G (B vs. A: OR = 1.28, 95%CI = 1.06-1.53, P < 0.001, I 2 = 63.1%) and -109 C/T (BB vs. AA+AB: OR = 1.58, 95%CI = 1.26-1.98, P < 0.001, I 2 = 66.4%) were risk factors for allergic diseases. Conclusion : Our meta-analysis suggests that polymorphisms in FcεRIβ, may be associated with the development of allergic diseases. ©2018 The Author(s).

Spaceflight Effects on Genetics and Plasmids of Streptomycetes

NASA Astrophysics Data System (ADS)

Voeikova, T. A.; Emelyanova, L. K.; Tyaglov, B. V.; Novikova, L. M.; Goins, T. L.; Pyle, B. H.

2008-06-01

In 2007, experiments with streptomycetes were conducted during a 12-day flight of the Russian Foton-M3 spacecraft. The flight (F), synchronous control (SC) and laboratory control (LC) specimens were kept at 30°C. The objective of the experiments was to study spaceflight effects on the streptomycetes growth, differentiation, pigmentation, enzyme formation, genetic stability of plasmid and crossing between strains. It was found that the frequency of strain Streptomyces lividans segregation, the enzyme synthesis, pigmentation, and the level of sporulation were higher in F than in SC organisms. The study of pIJ702 plasmid inheritance in S. lividans showed that the frequency of plasmid loss in F and LC was similar and lower than that in SC specimens. The study of melanin synthesis in S. lividans (pIJ702) strain demonstrated decreased melanin specific yield and increased biomass accumulation in F microorganisms. HPTLC analysis of melanin showed that the number, molecular mass and the percentage of fractions were similar in SC and LC but different in F organisms. The study of spaceflight effects on genetic recombination in crosses between Streptomyces coelicolor A3(2) auxotrophic mutants showed that the frequency of various recombinant classes in F specimens differed from that in SC and LC. The frequency of a distal donor marker entry to the recipient in F was higher than in SC and LC.

Genetically engineered hairy root cultures of Hyoscyamus senecionis and H. muticus: ploidy as a promising parameter in the metabolic engineering of tropane alkaloids.

PubMed

Dehghan, Esmaeil; Reed, Darwin W; Covello, Patrick S; Hasanpour, Zeinab; Palazon, Javier; Oksman-Caldentey, Kirsi-Marja; Ahmadi, Farajollah Shahriari

2017-10-01

Tetraploidy improves overexpression of h6h and scopolamine production of H. muticus, while in H. senecionis, pmt overexpression and elicitation can be used as effective methods for increasing tropane alkaloids. The effects of metabolic engineering in a polyploid context were studied by overexpression of h6h in the tetraploid hairy root cultures of H. muticus. Flow cytometry analysis indicated genetic stability in the majority of the clones, while only a few clones showed genetic instability. Among all the diploid and tetraploid clones, the highest level of h6h transgene expression and scopolamine accumulation was interestingly observed in the tetraploid clones of H. muticus. Therefore, metabolic engineering of the tropane biosynthetic pathway in polyploids is suggested as a potential system for increasing the production of tropane alkaloids. Transgenic hairy root cultures of Hyoscyamus senecionis were also established. While overexpression of pmt in H. senecionis was correlated with a sharp increase in hyoscyamine production, the h6h-overexpressing clones were not able to accumulate higher levels of scopolamine than the leaves of intact plants. Applying methyl jasmonate was followed by a sharp increase in the expression of pmt and a drop in the expression of tropinone reductase II (trII) which consequently resulted in the higher biosynthesis of hyoscyamine and total alkaloids in H. senecionis.

Genetic Techniques for Manipulation of the Phytosterol Biotransformation Strain Mycobacterium neoaurum NRRL B-3805.

PubMed

Loraine, Jessica K; Smith, Margaret C M

2017-01-01

Mycobacterium neoaurum is a saprophytic, soil-dwelling bacterium. The strain NRRL B-3805 converts phytosterols to androst-4-ene-3,17-dione (androstenedione; AD), a precursor of multiple C19 steroids of importance to industry. NRRL B-3805 itself is able to convert AD to other steroid products, including testosterone (Ts) and androst-1,4-diene-3,17-dione (androstadienedione; ADD). However to improve this strain for industrial use, genetic modification is a priority. In this chapter, we describe a range of genetic techniques that can be used for M. neoaurum NRRL B-3805. Methods for transformation, expression, and gene knockouts are presented as well as plasmid maintenance and stability.

Recognition of digital characteristics based new improved genetic algorithm

NASA Astrophysics Data System (ADS)

Wang, Meng; Xu, Guoqiang; Lin, Zihao

2017-08-01

In the field of digital signal processing, Estimating the characteristics of signal modulation parameters is an significant research direction. The paper determines the set of eigenvalue which can show the difference of the digital signal modulation based on the deep research of the new improved genetic algorithm. Firstly take them as the best gene pool; secondly, The best gene pool will be changed in the genetic evolvement by selecting, overlapping and eliminating each other; Finally, Adapting the strategy of futher enhance competition and punishment to more optimizer the gene pool and ensure each generation are of high quality gene. The simulation results show that this method not only has the global convergence, stability and faster convergence speed.

Plasmid Stability in Dried Cells of the Desert Cyanobacterium Chroococcidiopsis and its Potential for GFP Imaging of Survivors on Earth and in Space

NASA Astrophysics Data System (ADS)

Billi, Daniela

2012-06-01

Two GFP-based plasmids, namely pTTQ18-GFP-pDU1mini and pDUCA7-GFP, of about 7 kbp and 15 kbp respectively, able to replicate in Chroococcidiopsis sp. CCMEE 029 and CCMEE 123, were developed. Both plasmids were maintained in Chroococcidiopsis cells after 18 months of dry storage as demonstrated by colony PCR, plasmid restriction analysis, GFP imaging and colony-forming ability under selection of dried transformants; thus suggesting that strategies employed by this cyanobacterium to stabilize dried chromosomal DNA, must have protected plasmid DNA. The suitability of pDU1mini-plasmid for GFP tagging in Chroococcidiopsis was investigated by using the RecA homolog of Synechocystis sp. PCC 6803. After 2 months of dry storage, the presence of dried cells with a GFP-RecASyn distribution resembling that of hydrated cells, supported its capability of preventing desiccation-induced genome damage, whereas the rewetted cells with filamentous GFP-RecASyn structures revealed sub-lethal DNA damage. The long-term stability of plasmid DNA in dried Chroococcidiopsis has implication for space research, for example when investigating the recovery of dried cells after Martian and space simulations or when developing life support systems based on phototrophs with genetically enhanced stress tolerance and stored in the dry state for prolonged periods.

Chatter reduction in boring process by using piezoelectric shunt damping with experimental verification

NASA Astrophysics Data System (ADS)

Yigit, Ufuk; Cigeroglu, Ender; Budak, Erhan

2017-09-01

Chatter is a self-excited type of vibration that develops during machining due to process-structure dynamic interactions resulting in modulated chip thickness. Chatter is an important problem as it results in poor surface quality, reduced productivity and tool life. The stability of a cutting process is strongly influenced by the frequency response function (FRF) at the cutting point. In this study, the effect of piezoelectric shunt damping on chatter vibrations in a boring process is studied. In piezoelectric shunt damping method, an electrical impedance is connected to a piezoelectric transducer which is bonded on cutting tool. Electrical impedance of the circuit consisting of piezoceramic transducer and passive shunt is tuned to the desired natural frequency of the cutting tool in order to maximize damping. The optimum damping is achieved in analytical and finite element models (FEM) by using a genetic algorithm focusing on the real part of the tool point FRF rather than the amplitude. Later, a practical boring bar is considered where the optimum circuit parameters are obtained by the FEM. Afterwards, the effect of the optimized piezoelectric shunt damping on the dynamic rigidity and absolute stability limit of the cutting process are investigated experimentally by modal analysis and cutting tests. It is both theoretically and experimentally shown that application of piezoelectric shunt damping results in a significant increase in the absolute stability limit in boring operations.

Plasmid stability in dried cells of the desert cyanobacterium Chroococcidiopsis and its potential for GFP imaging of survivors on Earth and in space.

PubMed

Billi, Daniela

2012-06-01

Two GFP-based plasmids, namely pTTQ18-GFP-pDU1(mini) and pDUCA7-GFP, of about 7 kbp and 15 kbp respectively, able to replicate in Chroococcidiopsis sp. CCMEE 029 and CCMEE 123, were developed. Both plasmids were maintained in Chroococcidiopsis cells after 18 months of dry storage as demonstrated by colony PCR, plasmid restriction analysis, GFP imaging and colony-forming ability under selection of dried transformants; thus suggesting that strategies employed by this cyanobacterium to stabilize dried chromosomal DNA, must have protected plasmid DNA. The suitability of pDU1(mini)-plasmid for GFP tagging in Chroococcidiopsis was investigated by using the RecA homolog of Synechocystis sp. PCC 6803. After 2 months of dry storage, the presence of dried cells with a GFP-RecA(Syn) distribution resembling that of hydrated cells, supported its capability of preventing desiccation-induced genome damage, whereas the rewetted cells with filamentous GFP-RecA(Syn) structures revealed sub-lethal DNA damage. The long-term stability of plasmid DNA in dried Chroococcidiopsis has implication for space research, for example when investigating the recovery of dried cells after Martian and space simulations or when developing life support systems based on phototrophs with genetically enhanced stress tolerance and stored in the dry state for prolonged periods.

Application of Bounded Linear Stability Analysis Method for Metrics-Driven Adaptive Control

NASA Technical Reports Server (NTRS)

Bakhtiari-Nejad, Maryam; Nguyen, Nhan T.; Krishnakumar, Kalmanje

2009-01-01

This paper presents the application of Bounded Linear Stability Analysis (BLSA) method for metrics-driven adaptive control. The bounded linear stability analysis method is used for analyzing stability of adaptive control models, without linearizing the adaptive laws. Metrics-driven adaptive control introduces a notion that adaptation should be driven by some stability metrics to achieve robustness. By the application of bounded linear stability analysis method the adaptive gain is adjusted during the adaptation in order to meet certain phase margin requirements. Analysis of metrics-driven adaptive control is evaluated for a second order system that represents a pitch attitude control of a generic transport aircraft. The analysis shows that the system with the metrics-conforming variable adaptive gain becomes more robust to unmodeled dynamics or time delay. The effect of analysis time-window for BLSA is also evaluated in order to meet the stability margin criteria.

Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

MedlinePlus

... they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of this protein's most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin ...

p62/SQSTM1 enhances breast cancer stem-like properties by stabilizing MYC mRNA

PubMed Central

Xu, L-Z; Li, S-S; Zhou, W; Kang, Z-J; Zhang, Q-X; Kamran, M; Xu, J; Liang, D-P; Wang, C-L; Hou, Z-J; Wan, X-B; Wang, H-J; Lam, E W-F; Zhao, Z-W; Liu, Q

2017-01-01

Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24− fractions, mammospheres, ALDH1+ populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments. PMID:27345399

Selection and validation of reference genes for gene expression analysis in apomictic and sexual Cenchrus ciliaris

PubMed Central

2013-01-01

Background Apomixis is a naturally occurring asexual mode of seed reproduction resulting in offspring genetically identical to the maternal plant. Identifying differential gene expression patterns between apomictic and sexual plants is valuable to help deconstruct the trait. Quantitative RT-PCR (qRT-PCR) is a popular method for analyzing gene expression. Normalizing gene expression data using proper reference genes which show stable expression under investigated conditions is critical in qRT-PCR analysis. We used qRT-PCR to validate expression and stability of six potential reference genes (EF1alpha, EIF4A, UBCE, GAPDH, ACT2 and TUBA) in vegetative and reproductive tissues of B-2S and B-12-9 accessions of C. ciliaris. Findings Among tissue types evaluated, EF1alpha showed the highest level of expression while TUBA showed the lowest. When all tissue types were evaluated and compared between genotypes, EIF4A was the most stable reference gene. Gene expression stability for specific ovary stages of B-2S and B-12-9 was also determined. Except for TUBA, all other tested reference genes could be used for any stage-specific ovary tissue normalization, irrespective of the mode of reproduction. Conclusion Our gene expression stability assay using six reference genes, in sexual and apomictic accessions of C. ciliaris, suggests that EIF4A is the most stable gene across all tissue types analyzed. All other tested reference genes, with the exception of TUBA, could be used for gene expression comparison studies between sexual and apomictic ovaries over multiple developmental stages. This reference gene validation data in C. ciliaris will serve as an important base for future apomixis-related transcriptome data validation. PMID:24083672

Arc is a flexible modular protein capable of reversible self-oligomerization

PubMed Central

Myrum, Craig; Baumann, Anne; Bustad, Helene J.; Flydal, Marte Innselset; Mariaule, Vincent; Alvira, Sara; Cuéllar, Jorge; Haavik, Jan; Soulé, Jonathan; Valpuesta, José Maria; Márquez, José Antonio; Martinez, Aurora; Bramham, Clive R.

2015-01-01

The immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskeletal structures or other polyanionic surfaces, whereas the C-terminal domain is acidic and stabilized by ionic conditions that promote oligomerization. Upon binding of presenilin-1 (PS1) peptide, hArc undergoes a large structural change. A non-synonymous genetic variant of hArc (V231G) showed properties similar to the wild-type (WT) protein. We conclude that hArc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes. PMID:25748042

Multilevel population genetic analysis of vanA and vanB Enterococcus faecium causing nosocomial outbreaks in 27 countries (1986-2012).

PubMed

Freitas, Ana R; Tedim, Ana P; Francia, Maria V; Jensen, Lars B; Novais, Carla; Peixe, Luísa; Sánchez-Valenzuela, Antonio; Sundsfjord, Arnfinn; Hegstad, Kristin; Werner, Guido; Sadowy, Ewa; Hammerum, Anette M; Garcia-Migura, Lourdes; Willems, Rob J; Baquero, Fernando; Coque, Teresa M

2016-12-01

Vancomycin-resistant Enterococcus faecium (VREfm) have been increasingly reported since the 1980s. Despite the high number of published studies about VRE epidemiology, the dynamics and evolvability of these microorganisms are still not fully understood. A multilevel population genetic analysis of VREfm outbreak strains since 1986, representing the first comprehensive characterization of plasmid content in E. faecium, was performed to provide a detailed view of potential transmissible units. From a comprehensive MeSH search, we identified VREfm strains causing hospital outbreaks (1986-2012). In total, 53 VanA and 18 VanB isolates (27 countries, 5 continents) were analysed and 82 vancomycin-susceptible E. faecium (VSEfm) were included for comparison. Clonal relatedness was established by PFGE and MLST (goeBURST/Bayesian Analysis of Population Structure, BAPS). Characterization of van transposons (PCR mapping, RFLP, sequencing), plasmids (transfer, ClaI-RFLP, PCR typing of relaxases, replication-initiation proteins and toxin-antitoxin systems, hybridization, sequencing), bacteriocins and virulence determinants (PCR, hybridization, sequencing) was performed. VREfm were mainly associated with major human lineages ST17, ST18 and ST78. VREfm and VSEfm harboured plasmids of different families [RCR, small theta plasmids, RepA_N (pRUM/pLG1) and Inc18] able to yield mosaic elements. Tn1546-vanA was mainly located on pRUM/Axe-Txe (USA) and Inc18-pIP186 (Europe) plasmids. The VanB2 type (Tn5382/Tn1549) was predominant among VanB strains (chromosome and plasmids). Both strains and plasmids contributed to the spread and persistence of vancomycin resistance among E. faecium. Horizontal gene transfer events among genetic elements from different clonal lineages (same or different species) result in chimeras with different stability and host range, complicating the surveillance of epidemic plasmids. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Genome-wide survey and analysis of microsatellites in giant panda (Ailuropoda melanoleuca), with a focus on the applications of a novel microsatellite marker system.

PubMed

Huang, Jie; Li, Yu-Zhi; Du, Lian-Ming; Yang, Bo; Shen, Fu-Jun; Zhang, He-Min; Zhang, Zhi-He; Zhang, Xiu-Yue; Yue, Bi-Song

2015-02-07

The giant panda (Ailuropoda melanoleuca) is a critically endangered species endemic to China. Microsatellites have been preferred as the most popular molecular markers and proven effective in estimating population size, paternity test, genetic diversity for the critically endangered species. The availability of the giant panda complete genome sequences provided the opportunity to carry out genome-wide scans for all types of microsatellites markers, which now opens the way for the analysis and development of microsatellites in giant panda. By screening the whole genome sequence of giant panda in silico mining, we identified microsatellites in the genome of giant panda and analyzed their frequency and distribution in different genomic regions. Based on our search criteria, a repertoire of 855,058 SSRs was detected, with mono-nucleotides being the most abundant. SSRs were found in all genomic regions and were more abundant in non-coding regions than coding regions. A total of 160 primer pairs were designed to screen for polymorphic microsatellites using the selected tetranucleotide microsatellite sequences. The 51 novel polymorphic tetranucleotide microsatellite loci were discovered based on genotyping blood DNA from 22 captive giant pandas in this study. Finally, a total of 15 markers, which showed good polymorphism, stability, and repetition in faecal samples, were used to establish the novel microsatellite marker system for giant panda. Meanwhile, a genotyping database for Chengdu captive giant pandas (n = 57) were set up using this standardized system. What's more, a universal individual identification method was established and the genetic diversity were analysed in this study as the applications of this marker system. The microsatellite abundance and diversity were characterized in giant panda genomes. A total of 154,677 tetranucleotide microsatellites were identified and 15 of them were discovered as the polymorphic and stable loci. The individual identification method and the genetic diversity analysis method in this study provided adequate material for the future study of giant panda.

Assessment of genetic and epigenetic changes in virus-free garlic (Allium sativum L.) plants obtained by meristem culture followed by in vitro propagation.

PubMed

Gimenez, Magalí Diana; Yañez-Santos, Anahí Mara; Paz, Rosalía Cristina; Quiroga, Mariana Paola; Marfil, Carlos Federico; Conci, Vilma Cecilia; García-Lampasona, Sandra Claudia

2016-01-01

This is the first report assessing epigenetic variation in garlic. High genetic and epigenetic polymorphism during in vitro culture was detected.Sequencing of MSAP fragments revealed homology with ESTs. Garlic (Allium sativum) is a worldwide crop of economic importance susceptible to viral infections that can cause significant yield losses. Meristem tissue culture is the most employed method to sanitize elite cultivars.Often the virus-free garlic plants obtained are multiplied in vitro (micro propagation). However, it was reported that micro-propagation frequently produces somaclonal variation at the phenotypic level, which is an undesirable trait when breeders are seeking to maintain varietal stability. We employed amplification fragment length polymorphism and methylation sensitive amplified polymorphism (MSAP) methodologies to assess genetic and epigenetic modifications in two culture systems: virus-free plants obtained by meristem culture followed by in vitro multiplication and field culture. Our results suggest that garlic exhibits genetic and epigenetic polymorphism under field growing conditions. However, during in vitro culture system both kinds of polymorphisms intensify indicating that this system induces somaclonal variation. Furthermore, while genetic changes accumulated along the time of in vitro culture, epigenetic polymorphism reached the major variation at 6 months and then stabilize, being demethylation and CG methylation the principal conversions.Cloning and sequencing differentially methylated MSAP fragments allowed us to identify coding and unknown sequences of A. sativum, including sequences belonging to LTR Gypsy retrotransposons. Together, our results highlight that main changes occur in the initial 6 months of micro propagation. For the best of our knowledge, this is the first report on epigenetic assessment in garlic.

An integrated, structure- and energy-based view of the genetic code.

PubMed

Grosjean, Henri; Westhof, Eric

2016-09-30

The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson-Crick pairs in the codon-anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Slope Stability Analysis of Waste Dump in Sandstone Open Pit Osielec

NASA Astrophysics Data System (ADS)

Adamczyk, Justyna; Cała, Marek; Flisiak, Jerzy; Kolano, Malwina; Kowalski, Michał

2013-03-01

This paper presents the slope stability analysis for the current as well as projected (final) geometry of waste dump Sandstone Open Pit "Osielec". For the stability analysis six sections were selected. Then, the final geometry of the waste dump was designed and the stability analysis was conducted. On the basis of the analysis results the opportunities to improve the stability of the object were identified. The next issue addressed in the paper was to determine the proportion of the mixture containing mining and processing wastes, for which the waste dump remains stable. Stability calculations were carried out using Janbu method, which belongs to the limit equilibrium methods.

The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

PubMed Central

Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs. PMID:23593258

SSR allelic variation in almond (Prunus dulcis Mill.).

PubMed

Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

2006-01-01

Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

Genetic variation and evolutionary stability of the FMR1 CGG repeat in six closed human populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eichler, E.E.; Nelson, D.L.

1996-07-12

In an attempt to understand the allelic diversity and mutability of the human FMR1 CGG repeat, we have analyzed the AGG substructure of this locus within six genetically-closed populations (Mbuti pygmy, Baka pygmy, R. surui, Karitiana, Mayan, and Hutterite). Most alleles (61/92 or 66%) possessed two AGG interspersions occurring with a periodicity of one AGG every nine or ten CGG repeats, indicating that this pattern is highly conserved in all human populations. Significant differences in allele distribution were observed among the populations for rare variants possessing fewer or more AGG interruptions than the canonical FMR1 CGG repeat sequence. Comparisons ofmore » expected heterozygosity of the FMR1 CGG repeat locus with 30 other microsatellite loci, demonstrated remarkably similar levels of polymorphism within each population, suggesting that most FMR1 CGG repeat alleles mutate at rates indistinguishable from other microsatellite loci. A single allele (1 out of 92) was identified with a large uninterrupted tract of pure repeats (42 pure CGG triplets). Retrospective pedigree analysis indicated that this allele had been transmitted unstably. Although such alleles mutate rapidly and likely represent evolving premutations, our analysis suggests that in spite of the estimated frequency of their occurrence, these unstable alleles do not significantly alter the expected heterozygosity of the FMR1 CGG repeat in the human population. 45 refs., 1 fig., 2 tabs.« less

The Utility of Stage-specific Mid-to-late Drosophila Follicle Isolation

PubMed Central

Spracklen, Andrew J.; Tootle, Tina L.

2013-01-01

Drosophila oogenesis or follicle development has been widely used to advance the understanding of complex developmental and cell biologic processes. This methods paper describes how to isolate mid-to-late stage follicles (Stage 10B-14) and utilize them to provide new insights into the molecular and morphologic events occurring during tight windows of developmental time. Isolated follicles can be used for a variety of experimental techniques, including in vitro development assays, live imaging, mRNA expression analysis and western blot analysis of proteins. Follicles at Stage 10B (S10B) or later will complete development in culture; this allows one to combine genetic or pharmacologic perturbations with in vitro development to define the effects of such manipulations on the processes occurring during specific periods of development. Additionally, because these follicles develop in culture, they are ideally suited for live imaging studies, which often reveal new mechanisms that mediate morphological events. Isolated follicles can also be used for molecular analyses. For example, changes in gene expression that result from genetic perturbations can be defined for specific developmental windows. Additionally, protein level, stability, and/or posttranslational modification state during a particular stage of follicle development can be examined through western blot analyses. Thus, stage-specific isolation of Drosophila follicles provides a rich source of information into widely conserved processes of development and morphogenesis. PMID:24326735

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study

PubMed Central

Alemany, Silvia; Rijsdijk, Frühling V.; Haworth, Claire Margaret Alison; Fañanás, Lourdes; Plomin, Robert

2013-01-01

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added asa covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors. PMID:23627958

Ternary Bismuthide SrPtBi 2: Computation and Experiment in Synergism to Explore Solid-State Materials

DOE PAGES

Gui, Xin; Zhao, Xin; Sobczak, Zuzanna; ...

2018-02-14

A combination of theoretical calculation and the experimental synthesis to explore the new ternary compound is demonstrated in the Sr–Pt–Bi system. Because Pt–Bi is considered as a new critical charge-transfer pair for superconductivity, it inspired us to investigate the Sr–Pt–Bi system. With a thorough calculation of all the known stable/metastable compounds in the Sr–Pt–Bi system and crystal structure predictions, the thermodynamic stability of hypothetical stoichiometry, SrPtBi2, is determined. Following the high-temperature synthesis and crystallographic analysis, the first ternary bismuthide in Sr–Pt–Bi, SrPtBi2 was prepared, and the stoichiometry was confirmed experimentally. SrPtBi 2 crystallizes in the space group Pnma (S.G. 62,more » Pearson Symbol oP48), which matches well with theoretical prediction using an adaptive genetic algorithm. Using first-principles calculations, we demonstrate that the orthorhombic structure has lower formation energies than other 112 structure types, such as tetragonal BaMnBi 2 (CuSmP 2) and LaAuBi 2 (CuHfSi 2) structure types. The bonding analysis indicates that the Pt–Bi interactions play a critical role in structural stability. The physical property measurements show the metallic properties at the low temperature, which agrees with the electronic structure assessment.« less

Social evolution and genetic interactions in the short and long term.

PubMed

Van Cleve, Jeremy

2015-08-01

The evolution of social traits remains one of the most fascinating and feisty topics in evolutionary biology even after half a century of theoretical research. W.D. Hamilton shaped much of the field initially with his 1964 papers that laid out the foundation for understanding the effect of genetic relatedness on the evolution of social behavior. Early theoretical investigations revealed two critical assumptions required for Hamilton's rule to hold in dynamical models: weak selection and additive genetic interactions. However, only recently have analytical approaches from population genetics and evolutionary game theory developed sufficiently so that social evolution can be studied under the joint action of selection, mutation, and genetic drift. We review how these approaches suggest two timescales for evolution under weak mutation: (i) a short-term timescale where evolution occurs between a finite set of alleles, and (ii) a long-term timescale where a continuum of alleles are possible and populations evolve continuously from one monomorphic trait to another. We show how Hamilton's rule emerges from the short-term analysis under additivity and how non-additive genetic interactions can be accounted for more generally. This short-term approach reproduces, synthesizes, and generalizes many previous results including the one-third law from evolutionary game theory and risk dominance from economic game theory. Using the long-term approach, we illustrate how trait evolution can be described with a diffusion equation that is a stochastic analogue of the canonical equation of adaptive dynamics. Peaks in the stationary distribution of the diffusion capture classic notions of convergence stability from evolutionary game theory and generally depend on the additive genetic interactions inherent in Hamilton's rule. Surprisingly, the peaks of the long-term stationary distribution can predict the effects of simple kinds of non-additive interactions. Additionally, the peaks capture both weak and strong effects of social payoffs in a manner difficult to replicate with the short-term approach. Together, the results from the short and long-term approaches suggest both how Hamilton's insight may be robust in unexpected ways and how current analytical approaches can expand our understanding of social evolution far beyond Hamilton's original work. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic structure and breeding system in a social wasp and its social parasite

PubMed Central

2008-01-01

Background Social insects dominate ecological communities because of their sophisticated group behaviors. However, the intricate behaviors of social insects may be exploited by social parasites, which manipulate insect societies for their own benefit. Interactions between social parasites and their hosts lead to unusual coevolutionary dynamics that ultimately affect the breeding systems and population structures of both species. This study represents one of the first attempts to understand the population and colony genetic structure of a parasite and its host in a social wasp system. Results We used DNA microsatellite markers to investigate gene flow, genetic variation, and mating behavior of the facultative social parasite Vespula squamosa and its primary host, V. maculifrons. Our analyses of genetic variability uncovered that both species possessed similar amounts of genetic variation and failed to show genetic structure over the sampling area. Our analysis of mating system of V. maculifrons and V. squamosa revealed high levels of polyandry and no evidence for inbreeding in the two species. Moreover, we found no significant differences between estimates of worker relatedness in this study and a previous investigation conducted over two decades ago, suggesting that the selective pressures operating on queen mate number have remained constant. Finally, the distribution of queen mate number in both species deviated from simple expectations suggesting that mate number may be under stabilizing selection. Conclusion The general biology of V. squamosa has not changed substantially from that of a typical, nonparasitic Vespula wasp. For example, population sizes of the host and its parasite appear to be similar, in contrast to other social parasites, which often display lower population sizes than their hosts. In addition, parasitism has not caused the mating behavior of V. squamosa queens to deviate from the high levels of multiple mating that typify Vespula wasps. This stands in contrast to some socially parasitic ants, which revert to mating with few males. Overall, the general similarity of the genetic structure of V. maculifrons and V. squamosa presumably reflects the fact that V. squamosa is still capable of independent colony founding and thus reflects an intermediate stage in the evolution of social parasitism. PMID:18715511

PARTIAL RESTRAINING FORCE INTRODUCTION METHOD FOR DESIGNING CONSTRUCTION COUNTERMESURE ON ΔB METHOD

NASA Astrophysics Data System (ADS)

Nishiyama, Taku; Imanishi, Hajime; Chiba, Noriyuki; Ito, Takao

Landslide or slope failure is a three-dimensional movement phenomenon, thus a three-dimensional treatment makes it easier to understand stability. The ΔB method (simplified three-dimensional slope stability analysis method) is based on the limit equilibrium method and equals to an approximate three-dimensional slope stability analysis that extends two-dimensional cross-section stability analysis results to assess stability. This analysis can be conducted using conventional spreadsheets or two-dimensional slope stability computational software. This paper describes the concept of the partial restraining force in-troduction method for designing construction countermeasures using the distribution of the restraining force found along survey lines, which is based on the distribution of survey line safety factors derived from the above-stated analysis. This paper also presents the transverse distributive method of restraining force used for planning ground stabilizing on the basis of the example analysis.

The gene-environmental architecture of the development of adolescent substance use.

PubMed

Vitaro, Frank; Dickson, Daniel J; Brendgen, Mara; Laursen, Brett; Dionne, Ginette; Boivin, Michel

2018-02-19

Using a longitudinal twin design and a latent growth curve/autoregressive approach, this study examined the genetic-environmental architecture of substance use across adolescence. Self-reports of substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17 years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec, Canada. Substance use increased linearly across the adolescent years. ACE modeling revealed that genetic, as well as shared and non-shared environmental factors explained the overall level of substance use and that these same factors also partly accounted for growth in substance use from age 13 to 17. Additional genetic factors predicted the growth in substance use. Finally, autoregressive effects revealed age-specific non-shared environmental influences and, to a lesser degree, age-specific genetic influences, which together accounted for the stability of substance use across adolescence. The results support and expand the notion that genetic and environmental influences on substance use during adolescence are both developmentally stable and developmentally dynamic.

DIY series of genetic cassettes useful in construction of versatile vectors specific for Alphaproteobacteria.

PubMed

Dziewit, Lukasz; Adamczuk, Marcin; Szuplewska, Magdalena; Bartosik, Dariusz

2011-08-01

We have developed a DIY (Do It Yourself) series of genetic cassettes, which facilitate construction of novel versatile vectors for Alphaproteobacteria. All the cassettes are based on defined genetic modules derived from three natural plasmids of Paracoccus aminophilus JCM 7686. We have constructed over 50 DIY cassettes, which differ in structure and specific features. All of them are functional in eight strains representing three orders of Alphaproteobacteria: Rhodobacterales, Rhizobiales and Caulobacterales. Besides various replication and stabilization systems, many of the cassettes also contain selective markers appropriate for Alphaproteobacteria (40 cassettes) and genetic modules responsible for mobilization for conjugal transfer (24 cassettes). All the DIY cassettes are bordered by different types of polylinkers, which facilitate vector construction. Using these DIY cassettes, we have created a set of compatible Escherichia coli-Alphaproteobacteria mobilizable shuttle vectors (high or low copy number in E. coli), which will greatly assist the genetic manipulation of Alphaproteobacteria. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic and environmental influences on relationship between anxiety sensitivity and anxiety subscales in children

PubMed Central

Waszczuk, M.A.; Zavos, H.M.S.; Eley, T.C.

2013-01-01

Anxiety sensitivity, a belief that symptoms of anxiety are harmful, has been proposed to influence development of panic disorder. Recent research suggests it may be a vulnerability factor for many anxiety subtypes. Moderate genetic influences have been implicated for both anxiety sensitivity and anxiety, however, little is known about the aetiology of the relationship between these traits in children. Self-reports of anxiety sensitivity and anxiety symptoms were collected from approximately 300 twin pairs at two time points. Partial correlations indicated that anxiety sensitivity at age 8 was broadly associated with most anxiety subtypes at age 10 (r = 0.11–0.17, p < 0.05). The associations were largely unidirectional, underpinned by stable genetic influences. Non-shared environment had unique influences on variables. Phenotypic results showed that anxiety sensitivity is a broad predictor of anxiety symptoms in childhood. Genetic results suggest that childhood is a developmental period characterised by genetic stability and time-specific environmental influences on anxiety-related traits. PMID:23872507

Genetic and Environmental Contributions to Behavioral Stability and Change in Children 6-36 months of Age Using Louisville Twin Study Data.

PubMed

Davis, Deborah Winders; Finkel, Deborah; Turkheimer, Eric; Dickens, William

2015-11-01

The Infant Behavior Record (IBR) from the Bayley Scales of Infant Development has been used to study behavioral development since the 1960s. Matheny (1983) examined behavioral development at 6, 12, 18, and 24 months from the Louisville Twin Study (LTS). The extracted temperament scales included Task Orientation, Affect-Extraversion, and Activity. He concluded that monozygotic twins were more similar than same-sex dizygotic twins on these dimensions. Since this seminal work was published, a larger LTS sample and more advanced analytical methods are available. In the current analyses, Choleksy decomposition was applied to behavioral data (n = 1231) from twins 6-36 months. Different patterns of genetic continuity vs genetic innovations were identified for each IBR scale. Single common genetic and shared environmental factors explained cross-age twin similarity in the Activity scale. Multiple shared environmental factors and a single genetic factor coming on line at age 18 months contributed to Affect-Extraversion. A single shared environmental factor and multiple genetic factors explained cross-age twin similarity in Task Orientation.

Monoamine oxidase A polymorphism moderates stability of attention problems and susceptibility to life stress during adolescence.

PubMed

Zohsel, K; Bianchi, V; Mascheretti, S; Hohm, E; Schmidt, M H; Esser, G; Brandeis, D; Banaschewski, T; Nobile, M; Laucht, M

2015-11-01

Attention problems affect a substantial number of children and adolescents and are predictive of academic underachievement and lower global adaptive functioning. Considerable variability has been observed with regard to the individual development of attention problems over time. In particular, the period of adolescence is characterized by substantial maturation of executive functioning including attentional processing, with the influence of genetic and environmental factors on individual trajectories not yet well understood. In the present investigation, we evaluated whether the monoamine oxidase A functional promoter polymorphism, MAOA-LPR, plays a role in determining continuity of parent-rated attention problems during adolescence. At the same time, a potential effect of severe life events (SLEs) was taken into account. A multi-group path analysis was used in a sample of 234 adolescents (149 males, 85 females) who took part in an epidemiological cohort study at the ages of 11 and 15 years. Attention problems during early adolescence were found to be a strong predictor of attention problems in middle adolescence. However, in carriers of the MAOA-LPR low-activity variant (MAOA-L), stability was found to be significantly higher than in carriers of the high-activity variant (MAOA-H). Additionally, only in MAOA-L carriers did SLEs during adolescence significantly impact on attention problems at the age of 15 years, implying a possible gene × environment interaction. To conclude, we found evidence that attention problems during adolescence in carriers of the MAOA-L allele are particularly stable and malleable to life stressors. The present results underline the usefulness of applying a more dynamic GxE perspective. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

New Interview and Observation Measures of the Broader Autism Phenotype: Description of Strategy and Reliability Findings for the Interview Measures.

PubMed

Parr, Jeremy R; De Jonge, Maretha V; Wallace, Simon; Pickles, Andrew; Rutter, Michael L; Le Couteur, Ann S; van Engeland, Herman; Wittemeyer, Kerstin; McConachie, Helen; Roge, Bernadette; Mantoulan, Carine; Pedersen, Lennart; Isager, Torben; Poustka, Fritz; Bolte, Sven; Bolton, Patrick; Weisblatt, Emma; Green, Jonathan; Papanikolaou, Katerina; Baird, Gillian; Bailey, Anthony J

2015-10-01

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and describe the development strategy and findings from the interviews. International Molecular Genetic Study of Autism Consortium data were collected from families containing at least two individuals with autism. Comparison of the informant and self-report interviews was restricted to samples in which the interviews were undertaken by different researchers from that site (251 UK informants, 119 from the Netherlands). Researchers produced vignettes that were rated blind by others. Retest reliability was assessed in 45 participants. Agreement between live scoring and vignette ratings was very high. Retest stability for the interviews was high. Factor analysis indicated a first factor comprising social-communication items and rigidity (but not other repetitive domain items), and a second factor comprised mainly of reading and spelling impairments. Whole scale Cronbach's alphas were high for both interviews. The correlation between interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43); Kappa values for between-interview agreement on individual items were mainly low. The correlations between individual items and total score were moderate. The inclusion of several factor 2 items lowered the overall Cronbach's alpha for the total set. Both interview measures showed good reliability and substantial stability over time, but the findings were better for factor 1 than factor 2. We recommend factor 1 scores be used for characterising the BAP. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo.

PubMed

Wishart, Thomas M; Rooney, Timothy M; Lamont, Douglas J; Wright, Ann K; Morton, A Jennifer; Jackson, Mandy; Freeman, Marc R; Gillingwater, Thomas H

2012-01-01

Degeneration of synaptic and axonal compartments of neurons is an early event contributing to the pathogenesis of many neurodegenerative diseases, but the underlying molecular mechanisms remain unclear. Here, we demonstrate the effectiveness of a novel "top-down" approach for identifying proteins and functional pathways regulating neurodegeneration in distal compartments of neurons. A series of comparative quantitative proteomic screens on synapse-enriched fractions isolated from the mouse brain following injury identified dynamic perturbations occurring within the proteome during both initiation and onset phases of degeneration. In silico analyses highlighted significant clustering of proteins contributing to functional pathways regulating synaptic transmission and neurite development. Molecular markers of degeneration were conserved in injury and disease, with comparable responses observed in synapse-enriched fractions isolated from mouse models of Huntington's disease (HD) and spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying degeneration in axonal and synaptic compartments. Our study has identified conserved molecular responses occurring within synapse-enriched fractions of the mouse brain during the early stages of neurodegeneration, focused on functional networks modulating synaptic transmission and incorporating molecular chaperones, cytoskeletal modifiers, and calcium-binding proteins. We propose that the proteins and functional pathways identified in the current study represent attractive targets for developing therapeutics aimed at modulating synaptic and axonal stability and neurodegeneration in vivo.

The Genetic Blues: Understanding Genetic Principles Using a Practical Approach and a Historical Perspective.

ERIC Educational Resources Information Center

Mysliwiec, Tami H.

2003-01-01

Incorporates history and genetics to explain how genetic traits are passed on to the next generation by focusing on methemoglobinemia, a rare genetic disease, and discusses how oxygen is carried by hemoglobin. Includes individual pedigree analysis and class pedigree analysis. (YDS)

Genetic and environmental influences on personality trait stability and growth during the transition to adulthood: A three wave longitudinal study

PubMed Central

Hopwood, Christopher J.; Donnellan, M. Brent; Blonigen, Daniel M.; Krueger, Robert F.; McGue, Matt; Iacono, William G.; Burt, S. Alexandra

2010-01-01

During the transition to adulthood individuals typically settle into adult roles in love and work. This transition also involves significant changes in personality traits that are generally in the direction of greater maturity and increased stability. Competing hypotheses have been offered to account for these personality changes: the intrinsic maturation hypothesis suggests that change trajectories are endogenous, whereas the life-course hypothesis suggests that these changes occur because of transactions with the social environment. This study investigated the patterns and origins of personality trait changes from ages 17 to 29 using 3 waves of Multidimensional Personality Questionnaire data provided by twins. Results suggest that a) trait changes were more profound in the first relative to the second half of the transition to adulthood; b) traits tend to become more stable during the second half of this transition, with all the traits yielding retest correlations between .74 and .78; c) negative affectivity declined over time and constraint increased over time; minimal change was observed on agentic or communal aspects of positive affectivity; and d) both genetic and non-shared environmental factors accounted for personality changes. Overall, these genetically-informed results support a life-course perspective on personality development during the transition to adulthood. PMID:21244174

Genetic and environmental influences on personality trait stability and growth during the transition to adulthood: a three-wave longitudinal study.

PubMed

Hopwood, Christopher J; Donnellan, M Brent; Blonigen, Daniel M; Krueger, Robert F; McGue, Matt; Iacono, William G; Burt, S Alexandra

2011-03-01

During the transition to adulthood individuals typically settle into adult roles in love and work. This transition also involves significant changes in personality traits that are generally in the direction of greater maturity and increased stability. Competing hypotheses have been offered to account for these personality changes: The intrinsic maturation hypothesis suggests that change trajectories are endogenous, whereas the life-course hypothesis suggests that these changes occur because of transactions with the social environment. This study investigated the patterns and origins of personality trait changes from ages 17 to 29 using 3 waves of Multidimensional Personality Questionnaire data provided by twins. Results suggest that (a) trait changes were more profound in the first relative to the second half of the transition to adulthood; (b) traits tend to become more stable during the second half of this transition, with all the traits yielding retest correlations between .74 and .78; (c) Negative Affectivity declined over time, and Constraint increased over time; minimal change was observed on agentic or communal aspects of Positive Emotionality; and (d) both genetic and nonshared environmental factors accounted for personality changes. Overall, these genetically informed results support a life-course perspective on personality development during the transition to adulthood. (c) 2011 APA, all rights reserved

Determining Selection across Heterogeneous Landscapes: A Perturbation-Based Method and Its Application to Modeling Evolution in Space.

PubMed

Wickman, Jonas; Diehl, Sebastian; Blasius, Bernd; Klausmeier, Christopher A; Ryabov, Alexey B; Brännström, Åke

2017-04-01

Spatial structure can decisively influence the way evolutionary processes unfold. To date, several methods have been used to study evolution in spatial systems, including population genetics, quantitative genetics, moment-closure approximations, and individual-based models. Here we extend the study of spatial evolutionary dynamics to eco-evolutionary models based on reaction-diffusion equations and adaptive dynamics. Specifically, we derive expressions for the strength of directional and stabilizing/disruptive selection that apply both in continuous space and to metacommunities with symmetrical dispersal between patches. For directional selection on a quantitative trait, this yields a way to integrate local directional selection across space and determine whether the trait value will increase or decrease. The robustness of this prediction is validated against quantitative genetics. For stabilizing/disruptive selection, we show that spatial heterogeneity always contributes to disruptive selection and hence always promotes evolutionary branching. The expression for directional selection is numerically very efficient and hence lends itself to simulation studies of evolutionary community assembly. We illustrate the application and utility of the expressions for this purpose with two examples of the evolution of resource utilization. Finally, we outline the domain of applicability of reaction-diffusion equations as a modeling framework and discuss their limitations.

Environmental heterogeneity explains the genetic structure of Continental and Mediterranean populations of Fraxinus angustifolia Vahl.

PubMed

Temunović, Martina; Franjić, Jozo; Satovic, Zlatko; Grgurev, Marin; Frascaria-Lacoste, Nathalie; Fernández-Manjarrés, Juan F

2012-01-01

Tree species with wide distributions often exhibit different levels of genetic structuring correlated to their environment. However, understanding how environmental heterogeneity influences genetic variation is difficult because the effects of gene flow, drift and selection are confounded. We investigated the genetic variation and its ecological correlates in a wind-pollinated Mediterranean tree species, Fraxinus angustifolia Vahl, within a recognised glacial refugium in Croatia. We sampled 11 populations from environmentally divergent habitats within the Continental and Mediterranean biogeographical regions. We combined genetic data analyses based on nuclear microsatellite loci, multivariate statistics on environmental data and ecological niche modelling (ENM). We identified a geographic structure with a high genetic diversity and low differentiation in the Continental region, which contrasted with the significantly lower genetic diversity and higher population divergence in the Mediterranean region. The positive and significant correlation between environmental and genetic distances after controlling for geographic distance suggests an important influence of ecological divergence of the sites in shaping genetic variation. The ENM provided support for niche differentiation between the populations from the Continental and Mediterranean regions, suggesting that contemporary populations may represent two divergent ecotypes. Ecotype differentiation was also supported by multivariate environmental and genetic distance analyses. Our results suggest that despite extensive gene flow in continental areas, long-term stability of heterogeneous environments have likely promoted genetic divergence of ashes in this region and can explain the present-day genetic variation patterns of these ancient populations.

Environmental Heterogeneity Explains the Genetic Structure of Continental and Mediterranean Populations of Fraxinus angustifolia Vahl

PubMed Central

Temunović, Martina; Franjić, Jozo; Satovic, Zlatko; Grgurev, Marin; Frascaria-Lacoste, Nathalie; Fernández-Manjarrés, Juan F.

2012-01-01

Tree species with wide distributions often exhibit different levels of genetic structuring correlated to their environment. However, understanding how environmental heterogeneity influences genetic variation is difficult because the effects of gene flow, drift and selection are confounded. We investigated the genetic variation and its ecological correlates in a wind-pollinated Mediterranean tree species, Fraxinus angustifolia Vahl, within a recognised glacial refugium in Croatia. We sampled 11 populations from environmentally divergent habitats within the Continental and Mediterranean biogeographical regions. We combined genetic data analyses based on nuclear microsatellite loci, multivariate statistics on environmental data and ecological niche modelling (ENM). We identified a geographic structure with a high genetic diversity and low differentiation in the Continental region, which contrasted with the significantly lower genetic diversity and higher population divergence in the Mediterranean region. The positive and significant correlation between environmental and genetic distances after controlling for geographic distance suggests an important influence of ecological divergence of the sites in shaping genetic variation. The ENM provided support for niche differentiation between the populations from the Continental and Mediterranean regions, suggesting that contemporary populations may represent two divergent ecotypes. Ecotype differentiation was also supported by multivariate environmental and genetic distance analyses. Our results suggest that despite extensive gene flow in continental areas, long-term stability of heterogeneous environments have likely promoted genetic divergence of ashes in this region and can explain the present-day genetic variation patterns of these ancient populations. PMID:22905171

Genetic Transformation of an argB Mutant of Aspergillus oryzae

PubMed Central

Hahm, Young Tae; Batt, Carl A.

1988-01-01

An argB mutant of Aspergillus oryzae NRRL 492 has been genetically transformed with the Aspergillus nidulans argB gene. Protoplasts were generated with a combination of Novozyme 234 and β-glucuronidase and regenerated on sucrose-stabilized minimal medium without arginine as described for A. nidulans. A frequency of 5 to 10 transformants per μg of DNA was obtained; however, most transformants appeared abortive. The A. nidulans argB gene and vector sequences appeared to be integrated into the A. oryzae chromosome. Images PMID:16347669

Sequence-Specific Affinity Chromatography of Bacterial Small Regulatory RNA-Binding Proteins from Bacterial Cells.

PubMed

Gans, Jonathan; Osborne, Jonathan; Cheng, Juliet; Djapgne, Louise; Oglesby-Sherrouse, Amanda G

2018-01-01

Bacterial small RNA molecules (sRNAs) are increasingly recognized as central regulators of bacterial stress responses and pathogenesis. In many cases, RNA-binding proteins are critical for the stability and function of sRNAs. Previous studies have adopted strategies to genetically tag an sRNA of interest, allowing isolation of RNA-protein complexes from cells. Here we present a sequence-specific affinity purification protocol that requires no prior genetic manipulation of bacterial cells, allowing isolation of RNA-binding proteins bound to native RNA molecules.

Structure-activity relationships between sterols and their thermal stability in oil matrix.

PubMed

Hu, Yinzhou; Xu, Junli; Huang, Weisu; Zhao, Yajing; Li, Maiquan; Wang, Mengmeng; Zheng, Lufei; Lu, Baiyi

2018-08-30

Structure-activity relationships between 20 sterols and their thermal stabilities were studied in a model oil system. All sterol degradations were found to be consistent with a first-order kinetic model with determination of coefficient (R 2 ) higher than 0.9444. The number of double bonds in the sterol structure was negatively correlated with the thermal stability of sterol, whereas the length of the branch chain was positively correlated with the thermal stability of sterol. A quantitative structure-activity relationship (QSAR) model to predict thermal stability of sterol was developed by using partial least squares regression (PLSR) combined with genetic algorithm (GA). A regression model was built with R 2 of 0.806. Almost all sterol degradation constants can be predicted accurately with R 2 of cross-validation equals to 0.680. Four important variables were selected in optimal QSAR model and the selected variables were observed to be related with information indices, RDF descriptors, and 3D-MoRSE descriptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

High stability of nuclear microsatellite loci during the early stages of somatic embryogenesis in Norway spruce.

PubMed

Helmersson, Andreas; von Arnold, Sara; Burg, Kornel; Bozhkov, Peter V

2004-10-01

Somatic embryos of Norway spruce (Picea abies (L.) Karst.) differentiate from proembryogenic masses (PEMs), which are subject to autodestruction through programmed cell death. In PEMs, somatic embryo formation and activation of programmed cell death are interrelated processes. We sought to determine if activation of programmed cell death in PEMs is caused by genetic aberrations during somatic embryogenesis. Based on the finding that withdrawal of auxin and cytokinin induces programmed cell death in PEMs, 1-week-old cell suspensions were cultured in medium either with or without auxin and cytokinin and then transferred to maturation medium containing abscisic acid. We analyzed the stability of three nuclear simple sequence repeat (SSR) microsatellite markers at successive stages of somatic embryogenesis in two cell lines. There were no mutations at the SSR loci at any of the successive developmental stages from PEMs to cotyledonary embryos, irrespective of whether or not the proliferation medium in which cell suspensions had been cultured contained auxin or cytokinin. The morphologies of plants regenerated from the cultures were similar, although withdrawal of auxin and cytokinin significantly stimulated the yield of both embryos and plants. We conclude, therefore, that the high genetic stability of somatic embryos in Norway spruce is unaffected by the induction of programmed cell death caused by withdrawal of auxin and cytokinin.

Stabilizing selection on sperm number revealed by artificial selection and experimental evolution.

PubMed

Cattelan, Silvia; Di Nisio, Andrea; Pilastro, Andrea

2018-03-01

Sperm competition is taxonomically widespread in animals and is usually associated with large sperm production, being the number of sperm in the competing pool the prime predictor of fertilization success. Despite the strong postcopulatory selection acting directionally on sperm production, its genetic variance is often very high. This can be explained by trade-offs between sperm production and traits associated with mate acquisition or survival, that may contribute to generate an overall stabilizing selection. To investigate this hypothesis, we first artificially selected male guppies (Poecilia reticulata) for high and low sperm production for three generations, while simultaneously removing sexual selection. Then, we interrupted artificial selection and restored sexual selection. Sperm production responded to divergent selection in one generation, and when we restored sexual selection, both high and low lines converged back to the mean sperm production of the original population within two generations, indicating that sperm number is subject to strong stabilizing total sexual selection (i.e., selection acting simultaneously on all traits associated with reproductive success). We discuss the possible mechanisms responsible for the maintenance of high genetic variability in sperm production despite strong selection acting on it. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Genetic structure of Cantharellus formosus populations in a second-growth temperate rain forest of the Pacific Northwest

USGS Publications Warehouse

Redman, Regina S.; Ranson, Judith; Rodriguez, Rusty J.

2006-01-01

Cantharellus formosus growing on the Olympic Peninsula of the Pacific Northwest was sampled from September – November 1995 for genetic analysis. A total of ninety-six basidiomes from five clusters separated from one another by 3 - 25 meters were genetically characterized by PCR analysis of 13 arbitrary loci and rDNA sequences. The number of basidiomes in each cluster varied from 15 to 25 and genetic analysis delineated 15 genets among the clusters. Analysis of variance utilizing thirteen apPCR generated genetic molecular markers and PCR amplification of the ribosomal ITS regions indicated that 81.41% of the genetic variation occurred between clusters and 18.59% within clusters. Proximity of the basidiomes within a cluster was not an indicator of genotypic similarity. The molecular profiles of each cluster were distinct and defined as unique populations containing 2 - 6 genets. The monitoring and analysis of this species through non-lethal sampling and future applications is discussed.

GTSE1 tunes microtubule stability for chromosome alignment and segregation by inhibiting the microtubule depolymerase MCAK

PubMed Central

Bendre, Shweta; Hall, Conrad; Lin, Yu-Chih

2016-01-01

The dynamic regulation of microtubules (MTs) during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore MTs have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The MT depolymerase MCAK (mitotic centromere-associated kinesin) can influence CIN through its impact on MT stability, but how its potent activity is controlled in cells remains unclear. In this study, we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumors, regulates MT stability during mitosis by inhibiting MCAK MT depolymerase activity. Cells lacking GTSE1 have defects in chromosome alignment and spindle positioning as a result of MT instability caused by excess MCAK activity. Reducing GTSE1 levels in CIN cancer cell lines reduces chromosome missegregation defects, whereas artificially inducing GTSE1 levels in chromosomally stable cells elevates chromosome missegregation and CIN. Thus, GTSE1 inhibition of MCAK activity regulates the balance of MT stability that determines the fidelity of chromosome alignment, segregation, and chromosomal stability. PMID:27881713

Adjustment of Adaptive Gain with Bounded Linear Stability Analysis to Improve Time-Delay Margin for Metrics-Driven Adaptive Control

NASA Technical Reports Server (NTRS)

Bakhtiari-Nejad, Maryam; Nguyen, Nhan T.; Krishnakumar, Kalmanje Srinvas

2009-01-01

This paper presents the application of Bounded Linear Stability Analysis (BLSA) method for metrics driven adaptive control. The bounded linear stability analysis method is used for analyzing stability of adaptive control models, without linearizing the adaptive laws. Metrics-driven adaptive control introduces a notion that adaptation should be driven by some stability metrics to achieve robustness. By the application of bounded linear stability analysis method the adaptive gain is adjusted during the adaptation in order to meet certain phase margin requirements. Analysis of metrics-driven adaptive control is evaluated for a linear damaged twin-engine generic transport model of aircraft. The analysis shows that the system with the adjusted adaptive gain becomes more robust to unmodeled dynamics or time delay.

The use of genetics for the management of a recovering population: temporal assessment of migratory peregrine falcons in North America

USGS Publications Warehouse

Johnson, Jeff A.; Talbot, Sandra L.; Sage, George K.; Burnham, Kurt K.; Brown, Joseph W.; Maechtle, Tom L.; Seegar, William S.; Yates, Michael A.; Anderson, Bud; Mindell, David P.

2010-01-01

Background:Our ability to monitor populations or species that were once threatened or endangered and in the process of recovery is enhanced by using genetic methods to assess overall population stability and size over time. This can be accomplished most directly by obtaining genetic measures from temporally-spaced samples that reflect the overall stability of the population as given by changes in genetic diversity levels (allelic richness and heterozygosity), degree of population differentiation (FST and DEST), and effective population size (Ne). The primary goal of any recovery effort is to produce a long-term self-sustaining population, and these measures provide a metric by which we can gauge our progress and help make important management decisions. Methodology/Principal Findings:The peregrine falcon in North America (Falco peregrinus tundrius and anatum) was delisted in 1994 and 1999, respectively, and its abundance will be monitored by the species Recovery Team every three years until 2015. Although the United States Fish and Wildlife Service makes a distinction between tundrius and anatum subspecies, our genetic results based on eleven microsatellite loci, including those from Brown et al. (2007), suggest no differentiation and warrant delineation of a subspecies in its northern latitudinal distribution from Alaska through Canada into Greenland. Using temporal samples collected at Padre Island, Texas during migration (seven temporal time periods between 1985-2007), no significant differences in genetic diversity or significant population differentiation in allele frequencies between time periods were observed and were indistinguishable from those obtained from tundrius/anatum breeding locations throughout their northern distribution. Estimates of harmonic mean Ne were variable and imprecise, but always greater than 500 when employing multiple temporal genetic methods. These results, including those from simulations to assess the power of each method to estimate Ne, suggest a stable population consistent with data from field-based monitoring indicating that this species is stable or continuing to increase in abundance. Therefore, historic and continuing efforts to prevent the extinction of the peregrine falcon in North America appear successful, further highlighting the importance of archiving samples for continual assessment of population recovery and long-term viability.

Molecular Evolution and Genetic Analysis of the Major Capsid Protein VP1 of Duck Hepatitis A Viruses: Implications for Antigenic Stability

PubMed Central

Ma, Xiuli; Sheng, Zizhang; Huang, Bing; Qi, Lihong; Li, Yufeng; Yu, Kexiang; Liu, Cunxia; Qin, Zhuoming; Wang, Dan; Song, Minxun; Li, Feng

2015-01-01

The duck hepatitis A virus (DHAV), a member of the family Picornaviridae, is the major cause of outbreaks with high mortality rates in young ducklings. It has three distinctive serotypes and among them, serotypes 1 (DHAV-1) and 3 (DHAV-3) were recognized in China. To investigate evolutionary and antigenic properties of the major capsid protein VP1 of these two serotypes, a primary target of neutralizing antibodies, we determined the VP1 coding sequences of 19 DHAV-1 (spanning 2000-2012) and 11 DHAV-3 isolates (spanning 2008-2014) associated with disease outbreaks. By bioinformatics analysis of VP1 sequences of these isolates and other DHAV strains reported previously, we demonstrated that DHAV-1 viruses evolved into two genetic lineages, while DHAV-3 viruses exhibited three distinct lineages. The rate of nucleotide substitution for DHAV-1 VP1 genes was estimated to be 5.57 x 10-4 per site per year, which was about one-third times slower than that for DHAV-3 VP1 genes. The population dynamics analysis showed an upward trend for infection of DHAV-1 viruses over time with little change observed for DHAV-3 viruses. Antigenic study of representative DHAV-1 and DHAV-3 strains covering all observed major lineages revealed no detectable changes in viral neutralization properties within the serotype, despite the lack of cross-neutralization between serotypes 1 and 3 strains. Structural analysis identified VP1 mutations in DHAV-1 and DHAV-3 viruses that underpin the observed antigenic phenotypes. Results of our experiments described here shall give novel insights into evolution and antigenicity of duck picornaviruses. PMID:26173145

Effects of Replication and Transcription on DNA Structure-Related Genetic Instability.

PubMed

Wang, Guliang; Vasquez, Karen M

2017-01-05

Many repetitive sequences in the human genome can adopt conformations that differ from the canonical B-DNA double helix (i.e., non-B DNA), and can impact important biological processes such as DNA replication, transcription, recombination, telomere maintenance, viral integration, transposome activation, DNA damage and repair. Thus, non-B DNA-forming sequences have been implicated in genetic instability and disease development. In this article, we discuss the interactions of non-B DNA with the replication and/or transcription machinery, particularly in disease states (e.g., tumors) that can lead to an abnormal cellular environment, and how such interactions may alter DNA replication and transcription, leading to potential conflicts at non-B DNA regions, and eventually result in genetic stability and human disease.

Effects of Replication and Transcription on DNA Structure-Related Genetic Instability

PubMed Central

Wang, Guliang; Vasquez, Karen M.

2017-01-01

Many repetitive sequences in the human genome can adopt conformations that differ from the canonical B-DNA double helix (i.e., non-B DNA), and can impact important biological processes such as DNA replication, transcription, recombination, telomere maintenance, viral integration, transposome activation, DNA damage and repair. Thus, non-B DNA-forming sequences have been implicated in genetic instability and disease development. In this article, we discuss the interactions of non-B DNA with the replication and/or transcription machinery, particularly in disease states (e.g., tumors) that can lead to an abnormal cellular environment, and how such interactions may alter DNA replication and transcription, leading to potential conflicts at non-B DNA regions, and eventually result in genetic stability and human disease. PMID:28067787

Single cell assessment of yeast metabolic engineering for enhanced lipid production using Raman and AFM-IR imaging.

PubMed

Kochan, Kamila; Peng, Huadong; Wood, Bayden R; Haritos, Victoria S

2018-01-01

Biodiesel is a valuable renewable fuel made from derivatized fatty acids produced in plants, animals, and oleaginous microbes. Of the latter, yeasts are of special interest due to their wide use in biotechnology, ability to synthesize fatty acids and store large amounts of triacylglycerols while utilizing non-food carbon sources. While yeast efficiently produce lipids, genetic modification and indeed, lipid pathway metabolic engineering, is usually required for cost-effective production. Traditionally, gas chromatography (GC) is used to measure fatty acid production and to track the success of a metabolic engineering strategy in a microbial culture; here we have employed vibrational spectroscopy approaches at population and single cell level of engineered yeast while simultaneously investigating metabolite levels in subcellular structures. Firstly, a strong correlation ( r 2  > 0.99) was established between Fourier transform infrared (FTIR) lipid in intact cells and GC analysis of fatty acid methyl esters in the differently engineered strains. Confocal Raman spectroscopy of individual cells carrying genetic modifications to enhance fatty acid synthesis and lipid accumulation revealed changes to the lipid body (LB), the storage organelle for lipids in yeast, with their number increasing markedly (up to tenfold higher); LB size was almost double in the strain that also expressed a LB stabilizing gene but considerable variation was also noted between cells. Raman spectroscopy revealed a clear trend toward reduced unsaturated fatty acid content in lipids of cells carrying more complex metabolic engineering. Atomic force microscopy-infrared spectroscopy (AFM-IR) analysis of individual cells indicated large differences in subcellular constituents between strains: cells of the most highly engineered strain had elevated lipid and much reduced carbohydrate in their cytoplasm compared with unmodified cells. Vibrational spectroscopy analysis allowed the simultaneous measurement of strain variability in metabolite production and impact on cellular structures as a result of different gene introductions or knockouts, within a lipid metabolic engineering strategy and these inform the next steps in comprehensive lipid engineering. Additionally, single cell spectroscopic analysis measures heterogeneity in metabolite production across microbial cultures under genetic modification, an emerging issue for efficient biotechnological production.

Efficient micropropagation and assessment of genetic fidelity of Boerhaavia diffusa L- High trade medicinal plant.

PubMed

Patil, Kapil S; Bhalsing, Sanjivani R

2015-07-01

Boerhaavia diffusa L is a medicinal herb with immense pharmaceutical significance. The plant is used by many herbalist, Ayurvedic and pharmaceutical industries for production biopharmaceuticals. It is among the 46 medicinal plant species in high trade sourced mainly from wastelands and generally found in temperate regions of the world. However, the commercial bulk of this plant shows genetic variations which are the main constraint to use this plant as medicinal ingredient and to obtain high value products of pharmaceutical interest from this plant. In this study, we have regenerated the plant of Boerhaavia diffusa L through nodal explants and evaluated genetic fidelity of the micropropagated plants of Boerhaavia diffusa L with the help of random amplified polymorphic DNA (RAPD) markers. The results obtained using RAPD showed monomorphic banding pattern revealing genetic stability among the mother plant and in vitro regenerated plants of Boerhaavia diffusa L.

Assessment of genetic and epigenetic variation in hop plants regenerated from sequential subcultures of organogenic calli.

PubMed

Peredo, Elena L; Revilla, M Angeles; Arroyo-García, Rosa

2006-10-01

Organogenic calli induced from internodal segments were subcultured three times. Regenerated plants obtained from each subculture were analysed by molecular methods. No major genetic rearrangements were detected in the callus-derived plants since none of the amplified fragment-length polymorphism (AFLP) loci were found to be polymorphic. However, epigenetic changes due to a demethylation process were detected by methylation-sensitive amplified polymorphism (MSAP) technique. The results allowed inference of the possible relationship among the plants derived from different calli subcultures and the in vitro control. The plants recovered from the first and second callus subcultures clustered with the in vitro control pools in the phenogram while the regenerants from the third callus subculture showed the highest genetic distance with the controls. This is the first study reporting data about the genetic stability of callus-derived Humulus lupulus L. plants.

Impacts of biogeographic history and marginal population genetics on species range limits: a case study of Liriodendron chinense.

PubMed

Yang, Aihong; Dick, Christopher W; Yao, Xiaohong; Huang, Hongwen

2016-05-10

Species ranges are influenced by past climate oscillations, geographical constraints, and adaptive potential to colonize novel habitats at range limits. This study used Liriodendron chinense, an important temperate Asian tree species, as a model system to evaluate the roles of biogeographic history and marginal population genetics in determining range limits. We examined the demographic history and genetic diversity of 29 L. chinense populations using both chloroplast and nuclear microsatellite loci. Significant phylogeographic structure was recovered with haplotype clusters coinciding with major mountain regions. Long-term demographical stability was suggested by mismatch distribution analyses, neutrality tests, and ecological niche models (ENM) and suggested the existence of LGM refuges within mountain regions. Differences in genetic diversity between central and marginal populations were not significant for either genomic region. However, asymmetrical gene flow was inferred from central populations to marginal populations, which could potentially limit range adaptation and expansion of L. chinense.

Bioengineering strategies to generate artificial protein complexes.

PubMed

Kim, Heejae; Siu, Ka-Hei; Raeeszadeh-Sarmazdeh, Maryam; Sun, Qing; Chen, Qi; Chen, Wilfred

2015-08-01

For many applications, increasing synergy between distinct proteins through organization is important for the specificity, regulation, and overall reaction efficiency. Although there are many examples of protein complexes in nature, a generalized method to create these complexes remains elusive. Many conventional techniques such as random chemical conjugation, physical adsorption onto surfaces, and encapsulation within matrices are imprecise approaches and can lead to deactivation of protein native functionalities. More "bio-friendly" approaches such as genetically fused proteins and biological scaffolds often can result in low yields and low complex stability. Alternatively, site-specific protein conjugation or ligation can generate artificial protein complexes that preserve the native functionalities of protein domains and maintain stability through covalent bonds. In this review, we describe three distinct methods to synthesize artificial protein complexes (genetic incorPoration of unnatural amino acids to introduce bio-orthogonal azide and alkyne groups to proteins, split-intein based expressed protein ligation, and sortase mediated ligation) and highlight interesting applications for each technique. © 2015 Wiley Periodicals, Inc.

Metastable Pluripotent States in NOD Mouse Derived ES Cells

PubMed Central

Hanna, Jacob; Markoulaki, Styliani; Mitalipova, Maisam; Cheng, Albert W.; Cassady, John P.; Staerk, Judith; Carey, Bryce W.; Lengner, Christopher J.; Foreman, Ruth; Love, Jennifer; Gao, Qing; Kim, Jongpil; Jaenisch, Rudolf

2009-01-01

Embryonic stem (ES) cells are isolated from the inner cell mass (ICM) of blastocysts, whereas epiblast stem cells (EpiSCs) are derived from the post-implantation epiblast and display a restricted developmental potential. Here we characterize pluripotent states in the non-obese diabetic (NOD) mouse strain, which prior to this study was considered “non-permissive” for ES cell derivation. We find that NOD stem cells can be stabilized by providing constitutive expression of Klf4 or c-Myc or small molecules that can replace these factors during in vitro reprogramming. The NOD ES and iPS cells appear “metastable”, as they acquire an alternative EpiSC-like identity after removal of the exogenous factors, while their reintroduction converts the cells back to ICM-like pluripotency. Our findings suggest that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro, the stability of which is regulated by endogenous genetic determinants and can be modified by exogenous factors. PMID:19427283

A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury

PubMed Central

Koch, Marta; Nicolas, Maya; Zschaetzsch, Marlen; de Geest, Natalie; Claeys, Annelies; Yan, Jiekun; Morgan, Matthew J.; Erfurth, Maria-Luise; Holt, Matthew; Schmucker, Dietmar; Hassan, Bassem A.

2018-01-01

Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism. PMID:29472843

Dual-level regulation of ACC synthase activity by MPK3/MPK6 cascade and its downstream WRKY transcription factor during ethylene induction in Arabidopsis.

PubMed

Li, Guojing; Meng, Xiangzong; Wang, Ruigang; Mao, Guohong; Han, Ling; Liu, Yidong; Zhang, Shuqun

2012-06-01

Plants under pathogen attack produce high levels of ethylene, which plays important roles in plant immunity. Previously, we reported the involvement of ACS2 and ACS6, two Type I ACS isoforms, in Botrytis cinerea-induced ethylene biosynthesis and their regulation at the protein stability level by MPK3 and MPK6, two Arabidopsis pathogen-responsive mitogen-activated protein kinases (MAPKs). The residual ethylene induction in the acs2/acs6 double mutant suggests the involvement of additional ACS isoforms. It is also known that a subset of ACS genes, including ACS6, is transcriptionally induced in plants under stress or pathogen attack. However, the importance of ACS gene activation and the regulatory mechanism(s) are not clear. In this report, we demonstrate using genetic analysis that ACS7 and ACS11, two Type III ACS isoforms, and ACS8, a Type II ACS isoform, also contribute to the B. cinerea-induced ethylene production. In addition to post-translational regulation, transcriptional activation of the ACS genes also plays a critical role in sustaining high levels of ethylene induction. Interestingly, MPK3 and MPK6 not only control the stability of ACS2 and ACS6 proteins via direct protein phosphorylation but also regulate the expression of ACS2 and ACS6 genes. WRKY33, another MPK3/MPK6 substrate, is involved in the MPK3/MPK6-induced ACS2/ACS6 gene expression based on genetic analyses. Furthermore, chromatin-immunoprecipitation assay reveals the direct binding of WRKY33 to the W-boxes in the promoters of ACS2 and ACS6 genes in vivo, suggesting that WRKY33 is directly involved in the activation of ACS2 and ACS6 expression downstream of MPK3/MPK6 cascade in response to pathogen invasion. Regulation of ACS activity by MPK3/MPK6 at both transcriptional and protein stability levels plays a key role in determining the kinetics and magnitude of ethylene induction.

It was a first class start which laid the basis for a promising future: Experience from comparative studies on gravity related behavior in animals and consequences for future experiments

NASA Astrophysics Data System (ADS)

Horn, Eberhard R.

2000-01-01

The main title was chosen in imitation of the headline of a lecture given by H. S. Wolff at the ESA-Symposium ``Life Odyssey'' in Maastricht/NL (1999) to contrast his pessimistic view of the science output from biological microgravity studies during the past 25 years with an optimistic view of the author who had the opportunity for studies on the gravity sensory systems of developing vertebrates and insects during the space missions STS-55, STS-84, and STS-90, and who was stimulated by this experience to undertake any effort to extend these studies on the International Space Station ISS. We studied compensatory eye and head movements induced by a lateral roll of the animals, and we found that exposure to both microgravity and hypergravity affect their development. Future studies have to consider long-term exposures to altered gravitational conditions to find answers to two questions, the mechanisms of adaptation during exposure, and the degree of residual effects after becoming an adult animal and also after re-entry to IG-conditions. The main hypothesis on the development of animals in space is that a fertilized egg will be converted to a normal adult animal guided by physiological and morphological set-points which represent the genetic program. In case of developmental retardations or accelerations or otherwise occurring deviations from normal structural and physiological development during specific periods of the embryonic and postembryonic life, these genetically defined supervisors activate readaptive mechanisms which direct the developmental processes towards normality, i.e., stability. Thus, an orbit-stabilized organism will be dramatically disturbed after return to Earth. Because this failure will need support to reach neuronal stability, research has also to consider the analysis of mechanisms which are able to overcome these disturbances. This research will open the door to applications because it forms a bridge to human medicine with its analytical research on control procedures over neuropathological mechanisms. .

Unstalled flutter stability predictions and comparisons to test data for a composite prop-fan model

NASA Technical Reports Server (NTRS)

Turnberg, J. E.

1986-01-01

The aeroelastic stability analyses for three graphite/epoxy composite Prop-Fan designs and post-test stability analysis for one of the designs, the SR-3C-X2 are presented. It was shown that Prop-Fan stability can be effectively analyzed using the F203 modal aeroelastic stability analysis developed at Hamilton Standard and that first mode torsion-bending coupling has a direct effect on blade stability. Positive first mode torsion-bending coupling is a destabilizing factor and the minimization of this parameter will increase Prop-Fan stability. It was also shown that Prop-Fan stability analysis using F203 is sensitive to the blade modal data used as input. Calculated blade modal properties varied significantly with the structural analysis used, and these variations are reflected in the F203 calculations.

New insights into structural determinants of prion protein folding and stability.

PubMed

Benetti, Federico; Legname, Giuseppe

2015-01-01

Prions are the etiological agent of fatal neurodegenerative diseases called prion diseases or transmissible spongiform encephalopathies. These maladies can be sporadic, genetic or infectious disorders. Prions are due to post-translational modifications of the cellular prion protein leading to the formation of a β-sheet enriched conformer with altered biochemical properties. The molecular events causing prion formation in sporadic prion diseases are still elusive. Recently, we published a research elucidating the contribution of major structural determinants and environmental factors in prion protein folding and stability. Our study highlighted the crucial role of octarepeats in stabilizing prion protein; the presence of a highly enthalpically stable intermediate state in prion-susceptible species; and the role of disulfide bridge in preserving native fold thus avoiding the misfolding to a β-sheet enriched isoform. Taking advantage from these findings, in this work we present new insights into structural determinants of prion protein folding and stability.

Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy.

PubMed

Rietz, Anne; Li, Hongxia; Quist, Kevin M; Cherry, Jonathan J; Lorson, Christian L; Burnett, Barrington G; Kern, Nicholas L; Calder, Alyssa N; Fritsche, Melanie; Lusic, Hrvoje; Boaler, Patrick J; Choi, Sungwoon; Xing, Xuechao; Glicksman, Marcie A; Cuny, Gregory D; Androphy, Elliot J; Hodgetts, Kevin J

2017-06-08

Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing. Initially, we identified analog 4m that had good in vitro properties but low plasma and brain exposure in a mouse PK experiment due to short plasma stability; this was overcome by reversing the amide bond and changing the heterocycle. Thiazole 27 showed excellent in vitro properties and a promising mouse PK profile, making it suitable for in vivo testing. This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA.

System and method for embedding emotion in logic systems

NASA Technical Reports Server (NTRS)

Curtis, Steven A. (Inventor)

2012-01-01

A system, method, and computer readable-media for creating a stable synthetic neural system. The method includes training an intellectual choice-driven synthetic neural system (SNS), training an emotional rule-driven SNS by generating emotions from rules, incorporating the rule-driven SNS into the choice-driven SNS through an evolvable interface, and balancing the emotional SNS and the intellectual SNS to achieve stability in a nontrivial autonomous environment with a Stability Algorithm for Neural Entities (SANE). Generating emotions from rules can include coding the rules into the rule-driven SNS in a self-consistent way. Training the emotional rule-driven SNS can occur during a training stage in parallel with training the choice-driven SNS. The training stage can include a self assessment loop which measures performance characteristics of the rule-driven SNS against core genetic code. The method uses a stability threshold to measure stability of the incorporated rule-driven SNS and choice-driven SNS using SANE.

Characterization of bean (Phaseolus vulgaris L.) ecotype "Fagiolo occhio nero di Oliveto Citra" using agronomic, biochemical and molecular approaches.

PubMed

Zaccardelli, Massimo; Pentangelo, Alfonso; Tripodi, Pasquale

2013-09-15

Common bean (Phaseolus vulgaris) is the most important grain legume and plays a significant role in human nutrition being a major source of dietary protein and representing a rich source of minerals and certain vitamins. Several large germplasm collections have been established, which contain large amounts of genetic diversity, including wild and domesticated species. In this study agronomic, biochemical and molecular characterization of landrace bean named "Fagiolo occhio nero di Oliveto Citra" (Phaseolus vulgaris L.), is described. Seeds were obtained by local farmers and field trials were carried out during years 2009-2010, in the typical cultivation site (Oliveto Citra, Salerno Province), using two different densities of investment. During 2011, in order to evaluate the performance in different environments, field trials were conducted in three localities (Battipaglia, Oliveto Citra and Controne). Data analysis shows good adaptability across locations and similar grain yield using two spacing's of seeds. Morphological characterization and molecular analysis, using AFLP and Minisatellite molecular markers, were performed on ten "biotypes" collected from local farmers. Seeds characterization showed variability on the violet area surrounding the hilum (named as eye) while markers have provided useful information on relationships between biotypes. Biochemical analysis, which includes the contents of protein, minerals and antioxidants, shows how the composition is consistent with respect to other landraces and commercial cultivars. The landrace under study revealed genetic stability and good adaptation to cultivated environment with best performance in the native area. In addition, the bio-agronomic characteristics are in accord with studies reported in literature.

Markers of Psychological Differences and Social and Health Inequalities: Possible Genetic and Phenotypic Overlaps.

PubMed

Mõttus, René; Marioni, Riccardo; Deary, Ian J

2017-02-01

Associations between markers of ostensible psychological characteristics and social and health inequalities are pervasive but difficult to explain. In some cases, there may be causal influence flowing from social and health inequalities to psychological differences, whereas sometimes it may be the other way around. Here, we focus on the possibility that some markers that we often consider as indexing different domains of individual differences may in fact reflect at least partially overlapping genetic and/or phenotypic bases. For example, individual differences in cognitive abilities and educational attainment appear to reflect largely overlapping genetic influences, whereas cognitive abilities and health literacy may be almost identical phenomena at the phenotypic, never mind genetic, level. We make the case for employing molecular genetic data and quantitative genetic techniques to better understand the associations of psychological individual differences with social and health inequalities. We illustrate these arguments by using published findings from the Lothian Birth Cohort and the Generation Scotland studies. We also present novel findings pertaining to longitudinal stability and change in older age personality traits and some correlates of the change, molecular genetic data-based heritability estimates of Neuroticism and Extraversion, and the genetic correlations of these personality traits with markers of social and health inequalities. © 2015 The Authors. Journal of Personality published by Wiley Periodicals, Inc.

Estimating the actual subject-specific genetic correlations in behavior genetics.

PubMed

Molenaar, Peter C M

2012-10-01

Generalization of the standard behavior longitudinal genetic factor model for the analysis of interindividual phenotypic variation to a genetic state space model for the analysis of intraindividual variation enables the possibility to estimate subject-specific heritabilities.

The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing.

PubMed

Mao, Y; Tamura, T; Yuki, Y; Abe, D; Tamada, Y; Imoto, S; Tanaka, H; Homma, H; Tagawa, K; Miyano, S; Okazawa, H

2016-04-28

In this study, we identify signaling network of necrotic cell death induced by transcriptional repression (TRIAD) by α-amanitin (AMA), the selective RNA polymerase II inhibitor, as a model of neurodegenerative cell death. We performed genetic screen of a knockdown (KD) fly library by measuring the ratio of transformation from pupa to larva (PL ratio) under TRIAD, and selected the cell death-promoting genes. Systems biology analysis of the positive genes mapped on protein-protein interaction databases predicted the signaling network of TRIAD and the core pathway including heterogeneous nuclear ribonucleoproteins (hnRNPs) and huntingtin (Htt). RNA sequencing revealed that AMA impaired transcription and RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing molecule. The impairment in RNA splicing and PL ratio was rescued by overexpresion of hnRNP that had been also affected by transcriptional repression. Fly genetics with suppressor or expresser of Htt and hnRNP worsened or ameliorated the decreased PL ratio by AMA, respectively. Collectively, these results suggested involvement of RNA splicing and a regulatory role of the hnRNP-Htt axis in the process of the transcriptional repression-induced necrosis.