Endogenous Reference Genes and Their Quantitative Real-Time PCR Assays for Genetically Modified Bread Wheat (Triticum aestivum L.) Detection.

PubMed

Yang, Litao; Quan, Sheng; Zhang, Dabing

2017-01-01

Endogenous reference genes (ERG) and their derivate analytical methods are standard requirements for analysis of genetically modified organisms (GMOs). Development and validation of suitable ERGs is the primary step for establishing assays that monitoring the genetically modified (GM) contents in food/feed samples. Herein, we give a review of the ERGs currently used for GM wheat analysis, such as ACC1, PKABA1, ALMT1, and Waxy-D1, as well as their performances in GM wheat analysis. Also, we discussed one model for developing and validating one ideal RG for one plant species based on our previous research work.

Between myth and reality: genetically modified maize, an example of a sizeable scientific controversy.

PubMed

Wisniewski, Jean-Pierre; Frangne, Nathalie; Massonneau, Agnès; Dumas, Christian

2002-11-01

Maize is a major crop plant with essential agronomical interests and a model plant for genetic studies. With the development of plant genetic engineering technology, many transgenic strains of this monocotyledonous plant have been produced over the past decade. In particular, field-cultivated insect-resistant Bt-maize hybrids are at the centre of an intense debate between scientists and organizations recalcitrant to genetically modified organisms (GMOs). This debate, which addresses both safety and ethical aspects, has raised questions about the impact of genetically modified (GM) crops on the biodiversity of traditional landraces and on the environment. Here, we review some of the key points of maize genetic history as well as the methods used to stably transform this cereal. We describe the genetically engineered Bt-maizes available for field cultivation and we investigate the controversial reports on their impacts on non-target insects such as the monarch butterfly and on the flow of transgenes into Mexican maize landraces.

Possibility of modifying the growth trajectory in Raeini Cashmere goat.

PubMed

Ghiasi, Heydar; Mokhtari, M S

2018-03-27

The objective of this study was to investigate the possibility of modifying the growth trajectory in Raeini Cashmere goat breed. In total, 13,193 records on live body weight collected from 4788 Raeini Cashmere goats were used. According to Akanke's information criterion (AIC), the sing-trait random regression model included fourth-order Legendre polynomial for direct and maternal genetic effect; maternal and individual permanent environmental effect was the best model for estimating (co)variance components. The matrices of eigenvectors for (co)variances between random regression coefficients of direct additive genetic were used to calculate eigenfunctions, and different eigenvector indices were also constructed. The obtained results showed that the first eigenvalue explained 79.90% of total genetic variance. Therefore, changing the body weights applying the first eigenfunction will be obtained rapidly. Selection based on the first eigenvector will cause favorable positive genetic gains for all body weight considered from birth to 12 months of age. For modifying the growth trajectory in Raeini Cashmere goat, the selection should be based on the second eigenfunction. The second eigenvalue accounted for 14.41% of total genetic variance for body weights that is low in comparison with genetic variance explained by the first eigenvalue. The complex patterns of genetic change in growth trajectory observed under the third and fourth eigenfunction and low amount of genetic variance explained by the third and fourth eigenvalues.

Ghrelin and eating behavior: evidence and insights from genetically-modified mouse models

PubMed Central

Uchida, Aki; Zigman, Jeffrey M.; Perelló, Mario

2013-01-01

Ghrelin is an octanoylated peptide hormone, produced by endocrine cells of the stomach, which acts in the brain to increase food intake and body weight. Our understanding of the mechanisms underlying ghrelin's effects on eating behaviors has been greatly improved by the generation and study of several genetically manipulated mouse models. These models include mice overexpressing ghrelin and also mice with genetic deletion of ghrelin, the ghrelin receptor [the growth hormone secretagogue receptor (GHSR)] or the enzyme that post-translationally modifies ghrelin [ghrelin O-acyltransferase (GOAT)]. In addition, a GHSR-null mouse model in which GHSR transcription is globally blocked but can be cell-specifically reactivated in a Cre recombinase-mediated fashion has been generated. Here, we summarize findings obtained with these genetically manipulated mice, with the aim to highlight the significance of the ghrelin system in the regulation of both homeostatic and hedonic eating, including that occurring in the setting of chronic psychosocial stress. PMID:23882175

Effect of genetic background on the dystrophic phenotype in mdx mice

PubMed Central

Coley, William D.; Bogdanik, Laurent; Vila, Maria Candida; Yu, Qing; Van Der Meulen, Jack H.; Rayavarapu, Sree; Novak, James S.; Nearing, Marie; Quinn, James L.; Saunders, Allison; Dolan, Connor; Andrews, Whitney; Lammert, Catherine; Austin, Andrew; Partridge, Terence A.; Cox, Gregory A.; Lutz, Cathleen; Nagaraju, Kanneboyina

2016-01-01

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan-null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them with the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared with their respective control strains at multiple time points between 6 and 52 weeks of age. Skeletal and cardiac muscle function, inflammation, regeneration, histology and biochemistry were characterized. We found that D2-mdx mice showed significantly reduced skeletal muscle function as early as 7 weeks and reduced cardiac function by 28 weeks, suggesting that the disease phenotype is more severe than in B10-mdx mice. In addition, D2-mdx mice showed fewer central myonuclei and increased calcifications in the skeletal muscle, heart and diaphragm at 7 weeks, suggesting that their pathology is different from the B10-mdx mice. The new D2-mdx model with an earlier onset and more pronounced dystrophy phenotype may be useful for evaluating therapies that target cardiac and skeletal muscle function in dystrophin-deficient mice. Our data align the D2-mdx with Duchenne muscular dystrophy patients with the LTBP4 genetic modifier, making it one of the few instances of cross-species genetic modifiers of monogenic traits. PMID:26566673

Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis.

PubMed

Li, Jingting; Sen, George L

2015-12-14

Organotypic cultures allow the reconstitution of a 3D environment critical for cell-cell contact and cell-matrix interactions which mimics the function and physiology of their in vivo tissue counterparts. This is exemplified by organotypic skin cultures which faithfully recapitulates the epidermal differentiation and stratification program. Primary human epidermal keratinocytes are genetically manipulable through retroviruses where genes can be easily overexpressed or knocked down. These genetically modified keratinocytes can then be used to regenerate human epidermis in organotypic skin cultures providing a powerful model to study genetic pathways impacting epidermal growth, differentiation, and disease progression. The protocols presented here describe methods to prepare devitalized human dermis as well as to genetically manipulate primary human keratinocytes in order to generate organotypic skin cultures. Regenerated human skin can be used in downstream applications such as gene expression profiling, immunostaining, and chromatin immunoprecipitations followed by high throughput sequencing. Thus, generation of these genetically modified organotypic skin cultures will allow the determination of genes that are critical for maintaining skin homeostasis.

Unraveling Genetic Modifiers in the Gria4 Mouse Model of Absence Epilepsy

PubMed Central

Frankel, Wayne N.; Mahaffey, Connie L.; McGarr, Tracy C.; Beyer, Barbara J.; Letts, Verity A.

2014-01-01

Absence epilepsy (AE) is a common type of genetic generalized epilepsy (GGE), particularly in children. AE and GGE are complex genetic diseases with few causal variants identified to date. Gria4 deficient mice provide a model of AE, one for which the common laboratory inbred strain C3H/HeJ (HeJ) harbors a natural IAP retrotransposon insertion in Gria4 that reduces its expression 8-fold. Between C3H and non-seizing strains such as C57BL/6, genetic modifiers alter disease severity. Even C3H substrains have surprising variation in the duration and incidence of spike-wave discharges (SWD), the characteristic electroencephalographic feature of absence seizures. Here we discovered extensive IAP retrotransposition in the C3H substrain, and identified a HeJ-private IAP in the Pcnxl2 gene, which encodes a putative multi-transmembrane protein of unknown function, resulting in decreased expression. By creating new Pcnxl2 frameshift alleles using TALEN mutagenesis, we show that Pcnxl2 deficiency is responsible for mitigating the seizure phenotype – making Pcnxl2 the first known modifier gene for absence seizures in any species. This finding gave us a handle on genetic complexity between strains, directing us to use another C3H substrain to map additional modifiers including validation of a Chr 15 locus that profoundly affects the severity of SWD episodes. Together these new findings expand our knowledge of how natural variation modulates seizures, and highlights the feasibility of characterizing and validating modifiers in mouse strains and substrains in the post-genome sequence era. PMID:25010494

Detection of Genetically Modified Food: Has Your Food Been Genetically Modified?

ERIC Educational Resources Information Center

Brandner, Diana L.

2002-01-01

Explains the benefits and risks of genetically-modified foods and describes methods for genetically modifying food. Presents a laboratory experiment using a polymerase chain reaction (PCR) test to detect foreign DNA in genetically-modified food. (Contains 18 references.) (YDS)

Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

PubMed Central

Chang, Howard C.; Sen, Anindya; Kalloo, Geetika; Harris, Jevede; Barsby, Tom; Walsh, Melissa B.; Satterlee, John S.; Li, Chris; Van Vactor, David; Artavanis-Tsakonas, Spyros; Hart, Anne C.

2010-01-01

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species. PMID:21124729

Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.

PubMed

Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J; Davis, Brian W; Kornegay, Joe N

2016-08-22

Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.

Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury

PubMed Central

Quattrocelli, Mattia; Capote, Joanna; Ohiri, Joyce C.; Warner, James L.; Vo, Andy H.; Hadhazy, Michele; Demonbreun, Alexis R.; Spencer, Melissa J.; McNally, Elizabeth M.

2017-01-01

Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action. We found that excess osteopontin exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin reduced injury extent both in isolated myofibers and in muscle in vivo. We found that ablation of osteopontin was associated with reduced expression of TGFβ and TGFβ-associated pathways. We identified that increased TGFβ resulted in reduced expression of Anxa1 and Anxa6, genes encoding key components of the muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide a model in which a feed forward loop of TGFβ and osteopontin directly impacts the capacity of muscle to recover from injury, and identifies an intersection of genetic modifiers on muscular dystrophy. PMID:29065150

Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury.

PubMed

Quattrocelli, Mattia; Capote, Joanna; Ohiri, Joyce C; Warner, James L; Vo, Andy H; Earley, Judy U; Hadhazy, Michele; Demonbreun, Alexis R; Spencer, Melissa J; McNally, Elizabeth M

2017-10-01

Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action. We found that excess osteopontin exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin reduced injury extent both in isolated myofibers and in muscle in vivo. We found that ablation of osteopontin was associated with reduced expression of TGFβ and TGFβ-associated pathways. We identified that increased TGFβ resulted in reduced expression of Anxa1 and Anxa6, genes encoding key components of the muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide a model in which a feed forward loop of TGFβ and osteopontin directly impacts the capacity of muscle to recover from injury, and identifies an intersection of genetic modifiers on muscular dystrophy.

Attitudes towards genetically modified and organic foods.

PubMed

Saher, Marieke; Lindeman, Marjaana; Hursti, Ulla-Kaisa Koivisto

2006-05-01

Finnish students (N=3261) filled out a questionnaire on attitudes towards genetically modified and organic food, plus the rational-experiential inventory, the magical thinking about food and health scale, Schwartz's value survey and the behavioural inhibition scale. In addition, they reported their eating of meat. Structural equation modelling of these measures had greater explanatory power for attitudes towards genetically modified (GM) foods than for attitudes towards organic foods (OF). GM attitudes were best predicted by natural science education and magical food and health beliefs, which mediated the influence of thinking styles. Positive attitudes towards organic food, on the other hand, were more directly related to such individual differences as thinking styles and set of values. The results of the study indicate that OF attitudes are rooted in more fundamental personal attributes than GM attitudes, which are embedded in a more complex but also in a more modifiable network of characteristics.

Genetically engineered T cells to target EGFRvIII expressing glioblastoma.

PubMed

Bullain, Szofia S; Sahin, Ayguen; Szentirmai, Oszkar; Sanchez, Carlos; Lin, Ning; Baratta, Elizabeth; Waterman, Peter; Weissleder, Ralph; Mulligan, Richard C; Carter, Bob S

2009-09-01

Glioblastoma remains a significant therapeutic challenge, warranting further investigation of novel therapies. We describe an immunotherapeutic strategy to treat glioblastoma based on adoptive transfer of genetically modified T-lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta). After in vitro selection and expansion, MR1-zeta genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-delzeta). MR1-zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via adoptive transfer of genetically modified T cells may represent a new immunotherapy strategy with great potential for clinical applications.

Recognition of genetically modified product based on affinity propagation clustering and terahertz spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Jianjun; Kan, Jianquan

2018-04-01

In this paper, based on the terahertz spectrum, a new identification method of genetically modified material by support vector machine (SVM) based on affinity propagation clustering is proposed. This algorithm mainly uses affinity propagation clustering algorithm to make cluster analysis and labeling on unlabeled training samples, and in the iterative process, the existing SVM training data are continuously updated, when establishing the identification model, it does not need to manually label the training samples, thus, the error caused by the human labeled samples is reduced, and the identification accuracy of the model is greatly improved.

Farmers prevailing perception profiles regarding GM crops: A classification proposal.

PubMed

Almeida, Carla; Massarani, Luisa

2018-04-01

Genetically modified organisms have been at the centre of a major public controversy, involving different interests and actors. While much attention has been devoted to consumer views on genetically modified food, there have been few attempts to understand the perceptions of genetically modified technology among farmers. By investigating perceptions of genetically modified organisms among Brazilian farmers, we intend to contribute towards filling this gap and thereby add the views of this stakeholder group to the genetically modified debate. A comparative analysis of our data and data from other studies indicate there is a complex variety of views on genetically modified organisms among farmers. Despite this diversity, we found variations in such views occur within limited parameters, concerned principally with expectations or concrete experiences regarding the advantages of genetically modified crops, perceptions of risks associated with them, and ethical questions they raise. We then propose a classification of prevailing profiles to represent the spectrum of perceptions of genetically modified organisms among farmers.

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis.

PubMed

Riessland, Markus; Kaczmarek, Anna; Schneider, Svenja; Swoboda, Kathryn J; Löhr, Heiko; Bradler, Cathleen; Grysko, Vanessa; Dimitriadi, Maria; Hosseinibarkooie, Seyyedmohsen; Torres-Benito, Laura; Peters, Miriam; Upadhyay, Aaradhita; Biglari, Nasim; Kröber, Sandra; Hölker, Irmgard; Garbes, Lutz; Gilissen, Christian; Hoischen, Alexander; Nürnberg, Gudrun; Nürnberg, Peter; Walter, Michael; Rigo, Frank; Bennett, C Frank; Kye, Min Jeong; Hart, Anne C; Hammerschmidt, Matthias; Kloppenburg, Peter; Wirth, Brunhilde

2017-02-02

Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca 2+ -dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants.

PubMed

Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

2014-04-01

Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided.

A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants

PubMed Central

Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

2014-01-01

Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided. PMID:24834325

A nursing theory-guided framework for genetic and epigenetic research.

PubMed

Maki, Katherine A; DeVon, Holli A

2018-04-01

The notion that genetics, through natural selection, determines innate traits has led to much debate and divergence of thought on the impact of innate traits on the human phenotype. The purpose of this synthesis was to examine how innate theory informs genetic research and how understanding innate theory through the lens of Martha Rogers' theory of unitary human beings can offer a contemporary view of how innate traits can inform epigenetic and genetic research. We also propose a new conceptual model for genetic and epigenetic research. The philosophical, theoretical, and research literatures were examined for this synthesis. We have merged philosophical and conceptual phenomena from innate theory with the theory of unitary beings into the University of Illinois at Chicago model for genetic and epigenetic research. Innate traits are the cornerstone of the framework but may be modified epigenetically by biological, physiological, psychological, and social determinants as they are transcribed. These modifiers serve as important links between the concept of innate traits and epigenetic modifications, and, like the theory of unitary human beings, the process is understood in the context of individual and environmental interaction that has the potential to evolve as the determinants change. © 2018 John Wiley & Sons Ltd.

A modifier of Huntington's disease onset at the MLH1 locus.

PubMed

Lee, Jong-Min; Chao, Michael J; Harold, Denise; Abu Elneel, Kawther; Gillis, Tammy; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F

2017-10-01

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association analyses implicate a functional variant on ∼32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3'end of MLH1 and the 5'end of the neighboring LRRFIP2, and marked by an isoleucine-valine missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

PubMed Central

Sanchez-Dominguez, Celia N.; Reyes-Lopez, Miguel A.; Bustamante, Adriana; Cerda-Flores, Ricardo M.; Villalobos-Torres, Maria del C.; Gallardo-Blanco, Hugo L.; Rojas-Martinez, Augusto; Martinez-Rodriguez, Herminia G.; Barrera-Saldaña, Hugo A.; Ortiz-Lopez, Rocio

2014-01-01

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (−251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP. Results The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25–9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease. Conclusion An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients. PMID:24603877

[Consumer reaction to information on the labels of genetically modified food].

PubMed

Sebastian-Ponce, Miren Itxaso; Sanz-Valero, Javier; Wanden-Berghe, Carmina

2014-02-01

To analyze consumer opinion on genetically modified foods and the information included on the label. A systematic review of the scientific literature on genetically modified food labeling was conducted consulting bibliographic databases (Medline - via PubMed -, EMBASE, ISI-Web of knowledge, Cochrane Library Plus, FSTA, LILACS, CINAHL and AGRICOLA) using the descriptors "organisms, genetically modified" and "food labeling". The search covered the first available date, up to June 2012, selecting relevant articles written in English, Portuguese or Spanish. Forty articles were selected after applying the inclusion and exclusion criteria. All of them should have conducted a population-based intervention focused on consumer awareness of genetically modified foods and their need or not, to include this on the label. The consumers expressed a preference for non-genetically modified products, and added that they were prepared to pay more for this but, ultimately, the product bought was that with the best price, in a market which welcomes new technologies. In 18 of the articles, the population was in favor of obligatory labelling, and in six, in favor of this being voluntary; seven studies showed the consumer knew little about genetically modified food, and in three, the population underestimated the quantity they consumed. Price was an influencing factor in all cases. Label should be homogeneous and clarify the degree of tolerance of genetically modified products in humans, in comparison with those non-genetically modified. Label should also present the content or not of genetically modified products and how these commodities are produced and should be accompanied by the certifying entity and contact information. Consumers express their preference for non-genetically modified products and they even notice that they are willing to pay more for it, but eventually they buy the item with the best price, in a market that welcomes new technologies.

Acceptance of genetically modified foods: the relation between technology and evaluation.

PubMed

Tenbült, Petra; De Vries, Nanne K; van Breukelen, Gerard; Dreezens, Ellen; Martijn, Carolien

2008-07-01

This study investigates why consumers accept different genetically modified food products to different extents. The study shows that whether food products are genetically modified or not and whether they are processed or not are the two important features that affect the acceptance of food products and their evaluation (in terms of perceived healthiness, naturalness, necessity and tastiness). The extent to which these evaluation attributes and acceptance of a product are affected by genetic modification or processing depends on whether the product is negatively affected by the other technology: Any technological change to a 'natural' product (when nonprocessed products are genetically modified or when non-genetically modified products are processed) affect evaluation and acceptance stronger than a change to an technologically adapted product (when processed products are also genetically modified or vice versa). Furthermore, evaluation attributes appear to mediate the effects of genetic modification and processing on acceptance.

The regulation of agricultural biotechnology: science shows a better way.

PubMed

Miller, Henry I

2010-11-30

National and international regulation of recombinant DNA-modified, or 'genetically engineered' (also referred to as 'genetically modified' or GM), organisms is unscientific and illogical, a lamentable illustration of the maxim that bad science makes bad law. Instead of regulatory scrutiny that is proportional to risk, the degree of oversight is actually inversely proportional to risk. The current approach to regulation, which captures for case-by-case review organisms to be field tested or commercialized according to the techniques used to construct them rather than their properties, flies in the face of scientific consensus. This approach has been costly in terms of economic losses and human suffering. The poorest of the poor have suffered the most because of hugely inflated development costs of genetically engineered plants and food. A model for regulation of field trials known as the 'Stanford Model' is designed to assess risks of new agricultural introductions - whether or not the organisms are genetically engineered, and independent of the genetic modification techniques employed. It offers a scientific, rational, risk-based basis for field trial regulations. Using this sort of model for regulatory review would not only better protect human health and the environment, but would also permit more expeditious development and more widespread use of new plants and seeds. Copyright © 2010 Elsevier B.V. All rights reserved.

Genetically modified foods and allergy.

PubMed

Lee, T H; Ho, H K; Leung, T F

2017-06-01

2015 marked the 25th anniversary of the commercial use and availability of genetically modified crops. The area of planted biotech crops cultivated globally occupies a cumulative two billion hectares, equivalent to twice the land size of China or the United States. Foods derived from genetically modified plants are widely consumed in many countries and genetically modified soybean protein is extensively used in processed foods throughout the industrialised countries. Genetically modified food technology offers a possible solution to meet current and future challenges in food and medicine. Yet there is a strong undercurrent of anxiety that genetically modified foods are unsafe for human consumption, sometimes fuelled by criticisms based on little or no firm evidence. This has resulted in some countries turning away food destined for famine relief because of the perceived health risks of genetically modified foods. The major concerns include their possible allergenicity and toxicity despite the vigorous testing of genetically modified foods prior to marketing approval. It is imperative that scientists engage the public in a constructive evidence-based dialogue to address these concerns. At the same time, improved validated ways to test the safety of new foods should be developed. A post-launch strategy should be established routinely to allay concerns. Mandatory labelling of genetically modified ingredients should be adopted for the sake of transparency. Such ingredient listing and information facilitate tracing and recall if required.

Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model.

PubMed

Goodrich, L R; Hidaka, C; Robbins, P D; Evans, C H; Nixon, A J

2007-05-01

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral joint received 2 x 10(7) naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model. The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.

Detection of Genetically Modified Sugarcane by Using Terahertz Spectroscopy and Chemometrics

NASA Astrophysics Data System (ADS)

Liu, J.; Xie, H.; Zha, B.; Ding, W.; Luo, J.; Hu, C.

2018-03-01

A methodology is proposed to identify genetically modified sugarcane from non-genetically modified sugarcane by using terahertz spectroscopy and chemometrics techniques, including linear discriminant analysis (LDA), support vector machine-discriminant analysis (SVM-DA), and partial least squares-discriminant analysis (PLS-DA). The classification rate of the above mentioned methods is compared, and different types of preprocessing are considered. According to the experimental results, the best option is PLS-DA, with an identification rate of 98%. The results indicated that THz spectroscopy and chemometrics techniques are a powerful tool to identify genetically modified and non-genetically modified sugarcane.

[Ethical challenges of genetic manipulation and research with animals].

PubMed

Rodríguez Yunta, Eduardo

2012-01-01

Research with animals presents ethical questions both for being used as models of human diseases and for being a prerequisite for trials in humans, as in the introduction of genetic modifications. Some of these questions refer to the fact that, as models, they do not fully represent the human condition; that conducting toxicity tests causes great harm to animals; that their nature is altered by genetic modifications and that introducing genetically modified organisms is a risk. The use of animals in research for the benefit of humans imposes the moral responsibility to respect them, not making them suffer unnecessarily, since they are living beings capable of feeling.

Genetic Basis and Genetic Modifiers of β-Thalassemia and Sickle Cell Disease.

PubMed

Thein, Swee Lay

2017-01-01

β-thalassemia and sickle cell disease (SCD) are prototypical Mendelian single gene disorders, both caused by mutations affecting the adult β-globin gene. Despite the apparent genetic simplicity, both disorders display a remarkable spectrum of phenotypic severity and share two major genetic modifiers-α-globin genotype and innate ability to produce fetal hemoglobin (HbF, α 2 γ 2 ).This article provides an overview of the genetic basis for SCD and β-thalassemia, and genetic modifiers identified through phenotype correlation studies. Identification of the genetic variants modifying HbF production in combination with α-globin genotype provide some prediction of disease severity for β-thalassemia and SCD but generation of a personalized genetic risk score to inform prognosis and guide management requires a larger panel of genetic modifiers yet to be discovered.Nonetheless, genetic studies have been successful in characterizing some of the key variants and pathways involved in HbF regulation, providing new therapeutic targets for HbF reactivation.

Exploring Middle School Students' Understanding of Three Conceptual Models in Genetics

NASA Astrophysics Data System (ADS)

Bresler Freidenreich, Hava; Golan Duncan, Ravit; Shea, Nicole

2011-11-01

Genetics is the cornerstone of modern biology and a critical aspect of scientific literacy. Research has shown, however, that many high school graduates lack fundamental understandings in genetics necessary to make informed decisions about issues and emerging technologies in this domain, such as genetic screening, genetically modified foods, etc. Genetic literacy entails understanding three interrelated models: a genetic model that describes patterns of genetic inheritance, a meiotic model that describes the process by which genes are segregated into sex cells, and a molecular model that describes the mechanisms that link genotypes to phenotypes within an individual. Currently, much of genetics instruction, especially in terms of the molecular model, occurs at the high school level, and we know little about the ways in which middle school students can reason about these models. Furthermore, we do not know the extent to which carefully designed instruction can help younger students develop coherent and interrelated understandings in genetics. In this paper, we discuss a research study aimed at elucidating middle school students' abilities to reason about the three genetic models. As part of our research, we designed an eight-week inquiry unit that was implemented in a combined sixth- to eighth-grade science classroom. We describe our instructional design and report results based on an analysis of written assessments, clinical interviews, and artifacts of the unit. Our findings suggest that middle school students are able to successfully reason about all three genetic models.

Genetically engineered pigs as models for human disease

PubMed Central

Perleberg, Carolin; Kind, Alexander

2018-01-01

ABSTRACT Genetically modified animals are vital for gaining a proper understanding of disease mechanisms. Mice have long been the mainstay of basic research into a wide variety of diseases but are not always the most suitable means of translating basic knowledge into clinical application. The shortcomings of rodent preclinical studies are widely recognised, and regulatory agencies around the world now require preclinical trial data from nonrodent species. Pigs are well suited to biomedical research, sharing many similarities with humans, including body size, anatomical features, physiology and pathophysiology, and they already play an important role in translational studies. This role is set to increase as advanced genetic techniques simplify the generation of pigs with precisely tailored modifications designed to replicate lesions responsible for human disease. This article provides an overview of the most promising and clinically relevant genetically modified porcine models of human disease for translational biomedical research, including cardiovascular diseases, cancers, diabetes mellitus, Alzheimer's disease, cystic fibrosis and Duchenne muscular dystrophy. We briefly summarise the technologies involved and consider the future impact of recent technical advances. PMID:29419487

Yeast diversity and native vigor for flavor phenotypes.

PubMed

Carrau, Francisco; Gaggero, Carina; Aguilar, Pablo S

2015-03-01

Saccharomyces cerevisiae, the yeast used widely for beer, bread, cider, and wine production, is the most resourceful eukaryotic model used for genetic engineering. A typical concern about using engineered yeasts for food production might be negative consumer perception of genetically modified organisms. However, we believe the true pitfall of using genetically modified yeasts is their limited capacity to either refine or improve the sensory properties of fermented foods under real production conditions. Alternatively, yeast diversity screening to improve the aroma and flavors could offer groundbreaking opportunities in food biotechnology. We propose a 'Yeast Flavor Diversity Screening' strategy which integrates knowledge from sensory analysis and natural whole-genome evolution with information about flavor metabolic networks and their regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association between dietary fat intake and insulin resistance in Chinese child twins.

PubMed

Huang, Tao; Beaty, Terri; Li, Ji; Liu, Huijuan; Zhao, Wei; Wang, Youfa

2017-01-01

Dietary fat intake is correlated with increased insulin resistance (IR). However, it is unknown whether gene-diet interaction modulates the association. This study estimated heritability of IR measures and the related genetic correlations with fat intake, and tested whether dietary fat intake modifies the genetic influence on type 2 diabetes (T2D)-related traits in Chinese child twins. We included 622 twins aged 7-15 years (n 311 pairs, 162 monozygotic (MZ), 149 dizygotic (DZ)) from south-eastern China. Dietary factors were measured using FFQ. Structural equation models were fit using Mx statistical package. The intra-class correlation coefficients for all traits related to T2D were higher for MZ twins than for DZ twins. Dietary fat and fasting serum insulin (additive genetic correlation (r A) 0·20; 95 % CI 0·08, 0·43), glucose (r A 0·12; 95 % CI 0·01, 0·40), homoeostasis model of assessment-insulin resistance (Homa-IR) (r A 0·22; 95 % CI 0·10, 0·50) and the quantitative insulin sensitivity check index (Quicki) (r A -0·22; 95 % CI -0·40, 0·04) showed strong genetic correlations. Heritabilities of dietary fat intake, fasting glucose and insulin were estimated to be 52, 70 and 70 %, respectively. More than 70 % of the phenotypic correlations between dietary fat and insulin, glucose, Homa-IR and the Quicki index appeared to be mediated by shared genetic influence. Dietary fat significantly modified additive genetic effects on these quantitative traits associated with T2D. Analysis of Chinese twins yielded high estimates of heritability of dietary fat intake and IR. Genetic factors appear to contribute to a high proportion of the variance for both insulin sensitivity and IR. Dietary fat intake modifies the genetic influence on blood levels of insulin and glucose, Homa-IR and the Quicki index.

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

NASA Astrophysics Data System (ADS)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

Genetically modified mouse models to investigate thyroid development, function and growth.

PubMed

Löf, C; Patyra, K; Kero, A; Kero, J

2018-06-01

The thyroid gland produces thyroid hormones (TH), which are essential regulators for growth, development and metabolism. The thyroid is mainly controlled by the thyroid-stimulating hormone (TSH) that binds to its receptor (TSHR) on thyrocytes and mediates its action via different G protein-mediated signaling pathways. TSH primarily activates the G s -pathway, and at higher concentrations also the G q/11 -pathway, leading to an increase of intracellular cAMP and Ca 2+ , respectively. To date, the physiological importance of other G protein-mediated signaling pathways in thyrocytes is unclear. Congenital hypothyroidism (CH) is defined as the lack of TH at birth. In familial cases, high-throughput sequencing methods have facilitated the identification of novel mutations. Nevertheless, the precise etiology of CH yet remains unraveled in a proportion of cases. Genetically modified mouse models can reveal new pathophysiological mechanisms of thyroid diseases. Here, we will present an overview of genetic mouse models for thyroid diseases, which have provided crucial insights into thyroid gland development, function, and growth with a special focus on TSHR and microRNA signaling. Copyright © 2018 Elsevier Ltd. All rights reserved.

A natural compromise: a moderate solution to the GMO & "natural" labeling disputes.

PubMed

Amaru, Stephanie

2014-01-01

In the United States, genetically modified (GM) foods are labeled no differently from their natural counterparts, leaving consumers with no mechanism for deciphering genetically modified food content. The Food and Drug Administration (FDA) has not formally defined the term "natural," which is frequently used on food labels despite consumer confusion as to what it means. The FDA should initiate a notice and comment rulemaking addressing the narrow issue of whether use of the word "natural" should be permitted oil GM food labels. Prohibition of the use of"natural" on genetically modified foods would mitigate consumer deception regarding genetically modified food content without significantly disadvantaging genetically modified food producers.

Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases.

PubMed

Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

2014-08-01

The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%-5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. © 2014 Remy et al.; Published by Cold Spring Harbor Laboratory Press.

Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases

PubMed Central

Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J.; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

2014-01-01

The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%–5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. PMID:24989021

[Genetically modified plants and food safety. State of the art and discussion in the European Union].

PubMed

Schauzu, M

2004-09-01

Placing genetically modified (GM) plants and derived products on the European Union's (EU) market has been regulated by a Community Directive since 1990. This directive was complemented by a regulation specific for genetically modified and other novel foods in 1997. Specific labelling requirements have been applicable for GM foods since 1998. The law requires a pre-market safety assessment for which criteria have been elaborated and continuously adapted in accordance with the state of the art by national and international bodies and organisations. Consequently, only genetically modified products that have been demonstrated to be as safe as their conventional counterparts can be commercialized. However, the poor acceptance of genetically modified foods has led to a de facto moratorium since 1998. It is based on the lack of a qualified majority of EU member states necessary for authorization to place genetically modified plants and derived foods on the market. New Community Regulations are intended to end this moratorium by providing a harmonized and transparent safety assessment, a centralised authorization procedure, extended labelling provisions and a traceability system for genetically modified organisms (GMO) and derived food and feed.

Consumer reaction to information on the labels of genetically modified food

PubMed Central

Sebastian-Ponce, Miren Itxaso; Sanz-Valero, Javier; Wanden-Berghe, Carmina

2014-01-01

OBJECTIVE To analyze consumer opinion on genetically modified foods and the information included on the label. METHODS A systematic review of the scientific literature on genetically modified food labeling was conducted consulting bibliographic databases (Medline – via PubMed –, EMBASE, ISI-Web of knowledge, Cochrane Library Plus, FSTA, LILACS, CINAHL and AGRICOLA) using the descriptors “organisms, genetically modified” and “food labeling”. The search covered the first available date, up to June 2012, selecting relevant articles written in English, Portuguese or Spanish. RESULTS Forty articles were selected after applying the inclusion and exclusion criteria. All of them should have conducted a population-based intervention focused on consumer awareness of genetically modified foods and their need or not, to include this on the label. The consumers expressed a preference for non-genetically modified products, and added that they were prepared to pay more for this but, ultimately, the product bought was that with the best price, in a market which welcomes new technologies. In 18 of the articles, the population was in favor of obligatory labelling, and in six, in favor of this being voluntary; seven studies showed the consumer knew little about genetically modified food, and in three, the population underestimated the quantity they consumed. Price was an influencing factor in all cases. CONCLUSIONS Label should be homogeneous and clarify the degree of tolerance of genetically modified products in humans, in comparison with those non-genetically modified. Label should also present the content or not of genetically modified products and how these commodities are produced and should be accompanied by the certifying entity and contact information. Consumers express their preference for non-genetically modifiedproducts and they even notice that they are willing to pay more for it, but eventually they buy the item with the best price, in a market that welcomes new technologies. PMID:24789648

Modeling hygroelastic properties of genetically modified aspen

Treesearch

Laszlo Horvath; Perry Peralta; Ilona Peszlen; Levente Csoka; Balazs Horvath; Joseph Jakes

2012-01-01

Numerical and three-dimensional finite element models were developed to improve understanding of major factors affecting hygroelastic wood properties. Effects of chemical composition, microfibril angle, crystallinity, structure of microfibrils, moisture content, and hydrophilicity of the cell wall were included in the model. Wood from wild-type and decreased-lignin...

Not all GMOs are crop plants: non-plant GMO applications in agriculture.

PubMed

Hokanson, K E; Dawson, W O; Handler, A M; Schetelig, M F; St Leger, R J

2014-12-01

Since tools of modern biotechnology have become available, the most commonly applied and often discussed genetically modified organisms are genetically modified crop plants, although genetic engineering is also being used successfully in organisms other than plants, including bacteria, fungi, insects, and viruses. Many of these organisms, as with crop plants, are being engineered for applications in agriculture, to control plant insect pests or diseases. This paper reviews the genetically modified non-plant organisms that have been the subject of permit approvals for environmental release by the United States Department of Agriculture/Animal and Plant Health Inspection Service since the US began regulating genetically modified organisms. This is an indication of the breadth and progress of research in the area of non-plant genetically modified organisms. This review includes three examples of promising research on non-plant genetically modified organisms for application in agriculture: (1) insects for insect pest control using improved vector systems; (2) fungal pathogens of insects to control insect pests; and (3) virus for use as transient-expression vectors for disease control in plants.

Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries

DTIC Science & Technology

2010-07-01

TITLE: Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries PRINCIPAL INVESTIGATOR: David H. Sachs, M.D...4. TITLE AND SUBTITLE Genetically Modified Porcine Skin Grafts for Treatment of 5a. CONTRACT NUMBER Severe Burn Injuries 5b. GRANT NUMBER...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES Burns, skin grafts , genetic

The Case of the "Tainted" Taco Shells: A Case Study on Genetically Modified Foods

ERIC Educational Resources Information Center

Taylor, Ann T. S.

2004-01-01

This case study introduces students to the use of genetically modified foods. Students learn how genetically modified plants are made, and then they read primary literature papers to evaluate the environmental, economic, and health issues. (Contains 2 figures.)

Overview of the current status of genetically modified plants in Europe as compared to the USA.

PubMed

Brandt, Peter

2003-07-01

Genetically modified crops have been tested in 1,726 experimental releases in the EU member states and in 7,815 experimental releases in the USA. The global commercial cultivation area of genetically modified crops is likely to reach 50 million hectares in 2001, however, the commercial production of genetically modified crops in the EU amounts to only a few thousand hectares and accounts for only some 0.03% of the world production. A significant gap exists between the more than fifty genetically modified crop species already permitted to be cultivated and to be placed on the market in the USA, Canada and other countries and the five genetically modified crop species permitted for the same use in the EU member states, which are still pending inclusion in the Common Catalogue of agricultural plant species. The further development of the "green gene technology" in the EU will be a matter of public acceptance and administrative legislation.

Co-downregulation of the hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase and coumarate 3-hydroxylase significantly increases cellulose content in transgenic alfalfa (Medicago sativa L.).

PubMed

Tong, Zongyong; Li, Heng; Zhang, Rongxue; Ma, Lei; Dong, Jiangli; Wang, Tao

2015-10-01

Lignin is a component of the cell wall that is essential for growth, development, structure and pathogen resistance in plants, but high lignin is an obstacle to the conversion of cellulose to ethanol for biofuel. Genetically modifying lignin and cellulose contents can be a good approach to overcoming that obstacle. Alfalfa (Medicago sativa L.) is rich in lignocellulose biomass and used as a model plant for the genetic modification of lignin in this study. Two key enzymes in the lignin biosynthesis pathway-hydroxycinnamoyl -CoA:shikimate hydroxycinnamoyl transferase (HCT) and coumarate 3-hydroxylase (C3H)-were co-downregulated. Compared to wild-type plants, the lignin content in the modified strain was reduced by 38%, cellulose was increased by 86.1%, enzyme saccharification efficiency was increased by 10.9%, and cell wall digestibility was increased by 13.0%. The modified alfalfa exhibited a dwarf phenotype, but normal above ground biomass. This approach provides a new strategy for reducing lignin and increasing cellulose contents and creates a new genetically modified crop with enhanced value for biofuel. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Regulating genetically modified food. Policy trajectories, political culture, and risk perceptions in the U.S., Canada, and EU.

PubMed

Wohlers, Anton E

2010-09-01

This paper examines whether national differences in political culture add an explanatory dimension to the formulation of policy in the area of biotechnology, especially with respect to genetically modified food. The analysis links the formulation of protective regulatory policies governing genetically modified food to both country and region-specific differences in uncertainty tolerance levels and risk perceptions in the United States, Canada, and European Union. Based on polling data and document analysis, the findings illustrate that these differences matter. Following a mostly opportunistic risk perception within an environment of high tolerance for uncertainty, policymakers in the United States and Canada modified existing regulatory frameworks that govern genetically modified food in their respective countries. In contrast, the mostly cautious perception of new food technologies and low tolerance for uncertainty among European Union member states has contributed to the creation of elaborate and stringent regulatory policies governing genetically modified food.

Genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies.

PubMed

Hightower, Rylie M; Alexander, Matthew S

2018-01-01

Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes, including age of loss of ambulation, steroid responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. This review highlights recent findings on genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. Muscle Nerve 57: 6-15, 2018. © 2017 Wiley Periodicals, Inc.

Genetic Modifiers of Duchenne and Facioscapulohumeral Muscular Dystrophies

PubMed Central

Hightower, Rylie M.; Alexander, Matthew S.

2017-01-01

Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing (NGS) has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost, have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes including age of loss of ambulation, steroid-responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. Here we review and highlight recent findings on genetic modifiers of Duchenne and Facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. PMID:28877560

Monitoring the agricultural landscape for insect resistance

NASA Astrophysics Data System (ADS)

Casas, Joseph; Glaser, J. A.; Copenhaver, Ken

Farmers in 25 countries on six continents are using plant biotechnology to solve difficult crop production challenges and conserve the environment. In fact, 13.3 million farmers, which include 90 percent of the farming in developing countries, choose to plant biotech crops. Over the past decade, farmers increased area planted in genetically modified (GM) crops by more than 10 percent each year, thus increasing their farm income by more than 44 billion US dollars (1996-2007), and achieved economic, environmental and social benefits in crops such as soybeans, canola, corn and cotton. To date, total acres of biotech crops harvested exceed more than 2 billion with a proven 13-year history of safe use. Over the next decade, expanded adoption combined with current research on 57 crops in 63 countries will broaden the advantages of genetically modified foods for growers, consumers and the environment. Genetically modified (GM) crops with the ability to produce toxins lethal to specific insect pests are covering a larger percentage of the agricultural landscape every year. The United States department of Agriculture (USDA) estimated that 63 percent of corn and 65 percent of cotton contained these specific genetic traits in 2009. The toxins could protect billions of dollars of loss from insect damage for crops valued at greater than 165 billion US dollars in 2008. The stable and efficient production of these crops has taken on even more importance in recent years with their use, not only as a food source, but now also a source of fuel. It is in the best interest of the United States Environmental Protection Agency (USEPA) to ensure the continued efficacy of toxin producing GM crops as their use reduces pesticides harmful to humans and animals. However, population genetics models have indicated the risk of insect pests developing resistance to these toxins if a high percentage of acreage is grown in these crops. The USEPA is developing methods to monitor the agricultural landscape to ensure resistance is not developing. USEPA is teaming with NASA to perform this monitoring using models and NASA earth observation imagery from airborne and satellite platforms. Using multiple spatial, temporal and spectral resolutions, the project is monitoring the entire Midwestern "Corn Belt". By applying these methods, the project has successfully delineated insect infestations in genetically modified corn fields. Insect resistance development is expected to present itself as infestations thus indicating potential identification of resistance if it develops in genetically modified crops. The USEPA and NASA are currently considering the development of plans to potentially extend this aircraft research to other crops and develop a micro-satellite application.

Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins.

PubMed

Mustelin, L; Silventoinen, K; Pietiläinen, K; Rissanen, A; Kaprio, J

2009-01-01

Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC). The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975-1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models. The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r = -0.12) and females (r=-0.18), and between physical activity and BMI in females (r = -0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC. Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.

77 FR 7172 - Sequoyah National Wildlife Refuge, Sequoyah, Muskogee, and Haskell Counties, OK; Comprehensive...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

.... Scoping for the environmental assessment (EA) on use of specified genetically modified crops in... of genetically modified crops in association with the cooperative farming program was released on... assessment of using specified genetically modified crops into the CCP and determined that an environmental...

HYBRIDIZATION STUDY BETWEEN GENETICALLY MODIFIED BRASSICA NAPUS AND NON-GENETICALLY MODIFIED B. NAPUS AND B. RAPA

EPA Science Inventory

Gene exchange between cultivated crops and wild species has gained significance in recent years because of concerns regarding the potential for gene flow between genetically modified (GM) crops and their domesticated and wild relatives. As part of our ecological effects of gene ...

MATERNAL EFFECTS IN ADVANCED HYBRIDS OF GENETICALLY MODIFIED AND NON-GENETICALLY MODIFIED BRASSICA SPECIES

EPA Science Inventory

Identification of fitness traits potentially impacted by gene flow from genetically modified (GM) crops to compatible relatives is of interest in risk assessments for GM crops. Reciprocal crosses were made between GM canola, Brassica napus cv. RaideRR that expresses CP4 EPSPS fo...

Gene-environment interactions and construct validity in preclinical models of psychiatric disorders.

PubMed

Burrows, Emma L; McOmish, Caitlin E; Hannan, Anthony J

2011-08-01

The contributions of genetic risk factors to susceptibility for brain disorders are often so closely intertwined with environmental factors that studying genes in isolation cannot provide the full picture of pathogenesis. With recent advances in our understanding of psychiatric genetics and environmental modifiers we are now in a position to develop more accurate animal models of psychiatric disorders which exemplify the complex interaction of genes and environment. Here, we consider some of the insights that have emerged from studying the relationship between defined genetic alterations and environmental factors in rodent models. A key issue in such animal models is the optimization of construct validity, at both genetic and environmental levels. Standard housing of laboratory mice and rats generally includes ad libitum food access and limited opportunity for physical exercise, leading to metabolic dysfunction under control conditions, and thus reducing validity of animal models with respect to clinical populations. A related issue, of specific relevance to neuroscientists, is that most standard-housed rodents have limited opportunity for sensory and cognitive stimulation, which in turn provides reduced incentive for complex motor activity. Decades of research using environmental enrichment has demonstrated beneficial effects on brain and behavior in both wild-type and genetically modified rodent models, relative to standard-housed littermate controls. One interpretation of such studies is that environmentally enriched animals more closely approximate average human levels of cognitive and sensorimotor stimulation, whereas the standard housing currently used in most laboratories models a more sedentary state of reduced mental and physical activity and abnormal stress levels. The use of such standard housing as a single environmental variable may limit the capacity for preclinical models to translate into successful clinical trials. Therefore, there is a need to optimize 'environmental construct validity' in animal models, while maintaining comparability between laboratories, so as to ensure optimal scientific and medical outcomes. Utilizing more sophisticated models to elucidate the relative contributions of genetic and environmental factors will allow for improved construct, face and predictive validity, thus facilitating the identification of novel therapeutic targets. Copyright © 2010 Elsevier Inc. All rights reserved.

Genetic modifications of pigs for medicine and agriculture

PubMed Central

Whyte, Jeffrey J.; Prather, Randall S.

2011-01-01

SUMMARY Genetically modified swine hold great promise in the fields of agriculture and medicine. Currently, these swine are being used to optimize production of quality meat, to improve our understanding of the biology of disease resistance, and to reduced waste. In the field of biomedicine, swine are anatomically and physiologically analogous to humans. Alterations of key swine genes in disease pathways provide model animals to improve our understanding of the causes and potential treatments of many human genetic disorders. The completed sequencing of the swine genome will significantly enhance the specificity of genetic modifications, and allow for more accurate representations of human disease based on syntenic genes between the two species. Improvements in both methods of gene alteration and efficiency of model animal production are key to enabling routine use of these swine models in medicine and agriculture. PMID:21671302

Overview of Animal Models of Obesity

PubMed Central

Lutz, Thomas A.; Woods, Stephen C.

2012-01-01

This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

Development of an innovative immunoassay for CP4EPSPS and Cry1AB genetically modified protein detection and quantification.

PubMed

Ermolli, M; Prospero, A; Balla, B; Querci, M; Mazzeo, A; Van Den Eede, G

2006-09-01

An innovative immunoassay, called enzyme-linked immunoabsorbant assay (ELISA) Reverse, based on a new conformation of the solid phase, was developed. The solid support was expressly designed to be immersed directly in liquid samples to detect the presence of protein targets. Its application is proposed in those cases where a large number of samples have to be screened simultaneously or when the simultaneous detection of different proteins is required. As a first application, a quantitative immunoassay for Cry1AB protein in genetically modified maize was optimized. The method was tested using genetically modified organism concentrations from 0.1 to 2.0%. The limit of detection and limit of quantitation of the method were determined as 0.0056 and 0.0168 (expressed as the percentage of genetically modified organisms content), respectively. A qualitative multiplex assay to assess the presence of two genetically modified proteins simultaneously was also established for the case of the Cry1AB and the CP4EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) present in genetically modified maize and soy, respectively.

[Progress on biosafety assessment of marker genes in genetically modified foods].

PubMed

Yang, Lichen; Yang, Xiaoguang

2003-05-01

Marker genes are useful in facilitating the detection of genetically modified organisms(GMO). These genes play an important role during the early identification stage of GMO development, but they exist in the mature genetically modified crops. So the safety assessment of these genes could not be neglected. In this paper, all the study on the biosafety assessment of marker genes were reviewed, their possible hazards and risks were appraised, and the marker genes proved safe were list too. GMO Labeling the is one important regulations for the development of genetically modified foods in the market. The accurate detecting techniques for GMO are the basis for setting up labeling regulation. In addition, some methods used to remove marker genes in genetically modified foods were introduced in the paper, which can eliminate their biosafety concern thoroughly.

Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.

PubMed

Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C; Pinto, Ricardo Mouro

2017-02-01

Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. Copyright © 2017 by the Genetics Society of America.

Immunotoxicological evaluation of wheat genetically modified with TaDREB4 gene on BALB/c mice.

PubMed

Liang, Chun Lai; Zhang, Xiao Peng; Song, Yan; Jia, Xu Dong

2013-08-01

To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. Female mice weighing 18-22 g were divided into five groups (10 mice/group), which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat (the proportion is 76%) for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected. No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group. From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

[Genetically modified food--unnecessary controversy?].

PubMed

Tchórz, Michał; Radoniewicz-Chagowska, Anna; Lewandowska-Stanek, Hanna; Szponar, Elzbieta; Szponar, Jarosław

2012-01-01

Fast development of genetic engineering and biotechnology allows use of genetically modified organisms (GMO) more and more in different branches of science and economy. Every year we can see an increase of food amount produced with the use of modification of genetic material. In our supermarkets we can find brand new types of plants, products including genetically modified ingredients or meat from animals fed with food containing GMO. This article presents general information about genetically modified organisms, it also explains the range of genetic manipulation, use of newly developed products and current field area for GMO in the world. Based on scientific data the article presents benefits from development of biotechnology in reference to modified food. It also presents the voice of skeptics who are extremely concerned about the impact of those organisms on human health and natural environment. Problems that appear or can appear as a result of an increase of GMO are very important not only from a toxicologist's or a doctor's point of view but first of all from the point of view of ordinary consumers--all of us.

Testing the limits of the 'joint account' model of genetic information: a legal thought experiment.

PubMed

Foster, Charles; Herring, Jonathan; Boyd, Magnus

2015-05-01

We examine the likely reception in the courtroom of the 'joint account' model of genetic confidentiality. We conclude that the model, as modified by Gilbar and others, is workable and reflects, better than more conventional legal approaches, both the biological and psychological realities and the obligations owed under Articles 8 and 10 of the European Convention on Human Rights (ECHR). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genetic engineering including superseding microinjection: new ways to make GM pigs.

PubMed

Galli, Cesare; Perota, Andrea; Brunetti, Dario; Lagutina, Irina; Lazzari, Giovanna; Lucchini, Franco

2010-01-01

Techniques for genetic engineering of swine are providing genetically modified animals of importance for the field of xenotransplantation, animal models for human diseases and for a variety of research applications. Many of these modifications have been directed toward avoiding naturally existing cellular and antibody responses to species-specific antigens. A number of techniques are today available to engineering the genome of mammals, these range from the well established less efficient method of DNA microinjection into the zygote, the use of viral vectors, to the more recent use of somatic cell nuclear transfer. The use of enzymatic engineering that are being developed now will refine the precision of the genetic modification combined with the use of new vectors like transposons. The use of somatic cell nuclear transfer is currently the most efficient way to generate genetically modified pigs. The development of enzymatic engineering with zinc-finger nucleases, recombinases and transposons will revolutionize the field. Nevertheless, genetic engineering in large domesticated animals will remain a challenging task. Recent improvements in several fields of cell and molecular biology offer new promises and opportunities toward an easier, cost-effective and efficient generation of transgenic pigs. © 2010 John Wiley & Sons A/S.

The Future Can’t Wait

DTIC Science & Technology

2013-09-01

following the traditional model of development assistance. Although there can be no objective rubric ...suggests “corporations are people?” Is there a path to higher agricultural productivity, other than genetically modifying crops whose seeds do not

Gene-dietary fat interaction, bone mineral density and bone speed of sound in Children: a twin study in China

PubMed Central

Huang, Tao; Liu, Huijuan; Zhao, Wei; Li, Ji; Wang, Youfa

2015-01-01

Scope Dietary fat correlates with bone mineral density (BMD). We tested the association between fat intake and BMD, and tested if fat intake modified the degree of genetic influence on BMD and bone speed of sound (SOS). Methods and results We included 622 twins aged 7–15 y from South China. Data on anthropometry, dietary intake, BMD, and SOS were collected. Quantitative genetic analyses of structural equation models were fit using the Mx statistical package. The within-pair intra-class correlations (ICC) for BMD in DZ twins were nearly half of that for MZ twins (ICC=0.39 vs 0.70). The heritability of BMD and SOS were 71% and 79%. Phenotypic correlation between fat intake and SOS was significant (r=−0.19, p=0.04). SOS was negatively correlated with fat intake in boys (r=−0.11, p=0.05), but not in girls. Full Cholesky decomposition models showed SOS has a strong genetic correlation with fat intake (rA =−0.88, 95% CI=−0.94, 0.01); the environmental correlation between fat intake and SOS was weak (rE =−0.04, 95% CI=−0.20, 0.13). Fat intake modified the additive genetic effects on BMD. Conclusion Genetic factors explained 71% and 79% of individual variance in BMD and SOS, respectively. Low fat intake counteracts genetic predisposition to low BMD. PMID:25546604

LONG-DISTANCE GM POLLEN MOVEMENT OF CREEPING BENTGRASS USING MODELED WIND TRAJECTORY ANALYSIS

EPA Science Inventory

The importance of understanding the role of atmospheric conditions in pollen dispersal has grown in recent years with increased field-testing of genetically modified (GM) crop plants. An atmospheric model was used to characterize wind trajectories at 10 m and 100 m above GM polle...

Using genetically modified tomato crop plants with purple leaves for absolute weed/crop classification.

PubMed

Lati, Ran N; Filin, Sagi; Aly, Radi; Lande, Tal; Levin, Ilan; Eizenberg, Hanan

2014-07-01

Weed/crop classification is considered the main problem in developing precise weed-management methodologies, because both crops and weeds share similar hues. Great effort has been invested in the development of classification models, most based on expensive sensors and complicated algorithms. However, satisfactory results are not consistently obtained due to imaging conditions in the field. We report on an innovative approach that combines advances in genetic engineering and robust image-processing methods to detect weeds and distinguish them from crop plants by manipulating the crop's leaf color. We demonstrate this on genetically modified tomato (germplasm AN-113) which expresses a purple leaf color. An autonomous weed/crop classification is performed using an invariant-hue transformation that is applied to images acquired by a standard consumer camera (visible wavelength) and handles variations in illumination intensities. The integration of these methodologies is simple and effective, and classification results were accurate and stable under a wide range of imaging conditions. Using this approach, we simplify the most complicated stage in image-based weed/crop classification models. © 2013 Society of Chemical Industry.

Multiple organ histopathological changes in broiler chickens fed on genetically modified organism.

PubMed

Cîrnatu, Daniela; Jompan, A; Sin, Anca Ileana; Zugravu, Cornelia Aurelia

2011-01-01

Diet can influence the structural characteristics of internal organs. An experiment involving 130 meat broilers was conducted during 42 days (life term for a meat broiler) to study the effect of feed with protein from genetically modified soy. The 1-day-old birds were randomly allocated to five study groups, fed with soy, sunflower, wheat, fish flour, PC starter. In the diet of each group, an amount of protein from soy was replaced with genetically modified soy (I - 0%, II - 25%, III - 50%, IV - 75%, V - 100% protein from genetically modified soy). The level of protein in soy, either modified, or non-modified, was the same. Organs and carcass weights were measured at about 42 days of age of the birds and histopathology exams were performed during May-June 2009. No statistically significant differences were observed in mortality, growth performance variables or carcass and organ yields between broilers consuming diets produced with genetically modified soybean fractions and those consuming diets produced with near-isoline control soybean fractions. Inflammatory and degenerative liver lesions, muscle hypertrophy, hemorrhagic necrosis of bursa, kidney focal tubular necrosis, necrosis and superficial ulceration of bowel and pancreatic dystrophies were found in tissues from broilers fed on protein from genetically modified soy. Different types of lesions found in our study might be due to other causes (parasites, viral) superimposed but their presence exclusively in groups fed with modified soy raises some serious questions about the consequences of use of this type of feed.

A simulation study of mutations in the genetic regulatory hierarchy for butterfly eyespot focus determination.

PubMed

Marcus, Jeffrey M; Evans, Travis M

2008-09-01

The color patterns on the wings of butterflies have been an important model system in evolutionary developmental biology. A recent computational model tested genetic regulatory hierarchies hypothesized to underlie the formation of butterfly eyespot foci [Evans, T.M., Marcus, J.M., 2006. A simulation study of the genetic regulatory hierarchy for butterfly eyespot focus determination. Evol. Dev. 8, 273-283]. The computational model demonstrated that one proposed hierarchy was incapable of reproducing the known patterns of gene expression associated with eyespot focus determination in wild-type butterflies, but that two slightly modified alternative hierarchies were capable of reproducing all of the known gene expressions patterns. Here we extend the computational models previously implemented in Delphi 2.0 to two mutants derived from the squinting bush brown butterfly (Bicyclus anynana). These two mutants, comet and Cyclops, have aberrantly shaped eyespot foci that are produced by different mechanisms. The comet mutation appears to produce a modified interaction between the wing margin and the eyespot focus that results in a series of comet-shaped eyespot foci. The Cyclops mutation causes the failure of wing vein formation between two adjacent wing-cells and the fusion of two adjacent eyespot foci to form a single large elongated focus in their place. The computational approach to modeling pattern formation in these mutants allows us to make predictions about patterns of gene expression, which are largely unstudied in butterfly mutants. It also suggests a critical experiment that will allow us to distinguish between two hypothesized genetic regulatory hierarchies that may underlie all butterfly eyespot foci.

Current issues connected with usage of genetically modified crops in production of feed and livestock feeding.

PubMed

Kwiatek, K; Mazur, M; Sieradzki, Z

2008-01-01

Progress, which is brought by new advances in modern molecular biology, allowed interference in the genome of live organisms and gene manipulation. Introducing new genes to the recipient organism enables to give them new features, absent before. Continuous increase in the area of the biotech crops triggers continuous discussion about safety of genetically modified (GM) crops, including food and feed derived from them. Important issue connected with cultivation of genetically modified crops is a horizontal gene transfer and a bacterial antibiotic resistance. Discussion about safety of GM crops concerns also food allergies caused by eating genetically modified food. The problem of genetic modifications of GM crops used for livestock feeding is widely discussed, taking into account Polish feed law.

Investigation of brain science and neurological/psychiatric disorders using genetically modified non-human primates.

PubMed

Okano, Hideyuki; Kishi, Noriyuki

2018-06-01

Although mice have been the most frequently used experimental animals in many research fields due to well-established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying future models for delivering genetic services: a nominal group study in primary care

PubMed Central

Elwyn, Glyn; Edwards, Adrian; Iredale, Rachel; Davies, Peter; Gray, Jonathon

2005-01-01

Background To enable primary care medical practitioners to generate a range of possible service delivery models for genetic counselling services and critically assess their suitability. Methods Modified nominal group technique using in primary care professional development workshops. Results 37 general practitioners in Wales, United Kingdom too part in the nominal group process. The practitioners who attended did not believe current systems were sufficient to meet anticipated demand for genetic services. A wide range of different service models was proposed, although no single option emerged as a clear preference. No argument was put forward for genetic assessment and counselling being central to family practice, neither was there a voice for the view that the family doctor should become skilled at advising patients about predictive genetic testing and be able to counsel patients about the wider implications of genetic testing for patients and their family members, even for areas such as common cancers. Nevertheless, all the preferred models put a high priority on providing the service in the community, and often co-located in primary care, by clinicians who had developed expertise. Conclusion There is a need for a wider debate about how healthcare systems address individual concerns about genetic concerns and risk, especially given the increasing commercial marketing of genetic tests. PMID:15831099

Detection and traceability of genetically modified organisms in the food production chain.

PubMed

Miraglia, M; Berdal, K G; Brera, C; Corbisier, P; Holst-Jensen, A; Kok, E J; Marvin, H J P; Schimmel, H; Rentsch, J; van Rie, J P P F; Zagon, J

2004-07-01

Both labelling and traceability of genetically modified organisms are current issues that are considered in trade and regulation. Currently, labelling of genetically modified foods containing detectable transgenic material is required by EU legislation. A proposed package of legislation would extend this labelling to foods without any traces of transgenics. These new legislations would also impose labelling and a traceability system based on documentation throughout the food and feed manufacture system. The regulatory issues of risk analysis and labelling are currently harmonised by Codex Alimentarius. The implementation and maintenance of the regulations necessitates sampling protocols and analytical methodologies that allow for accurate determination of the content of genetically modified organisms within a food and feed sample. Current methodologies for the analysis of genetically modified organisms are focused on either one of two targets, the transgenic DNA inserted- or the novel protein(s) expressed- in a genetically modified product. For most DNA-based detection methods, the polymerase chain reaction is employed. Items that need consideration in the use of DNA-based detection methods include the specificity, sensitivity, matrix effects, internal reference DNA, availability of external reference materials, hemizygosity versus homozygosity, extrachromosomal DNA, and international harmonisation. For most protein-based methods, enzyme-linked immunosorbent assays with antibodies binding the novel protein are employed. Consideration should be given to the selection of the antigen bound by the antibody, accuracy, validation, and matrix effects. Currently, validation of detection methods for analysis of genetically modified organisms is taking place. In addition, new methodologies are developed, including the use of microarrays, mass spectrometry, and surface plasmon resonance. Challenges for GMO detection include the detection of transgenic material in materials with varying chromosome numbers. The existing and proposed regulatory EU requirements for traceability of genetically modified products fit within a broader tendency towards traceability of foods in general and, commercially, towards products that can be distinguished from each other. Traceability systems document the history of a product and may serve the purpose of both marketing and health protection. In this framework, segregation and identity preservation systems allow for the separation of genetically modified and non-modified products from "farm to fork". Implementation of these systems comes with specific technical requirements for each particular step of the food processing chain. In addition, the feasibility of traceability systems depends on a number of factors, including unique identifiers for each genetically modified product, detection methods, permissible levels of contamination, and financial costs. In conclusion, progress has been achieved in the field of sampling, detection, and traceability of genetically modified products, while some issues remain to be solved. For success, much will depend on the threshold level for adventitious contamination set by legislation. Copryright 2004 Elsevier Ltd.

[Assessment of allergenicity of genetically modified food crops].

PubMed

Schauzu, M; Pöting, A; Rubin, D; Lampen, A

2012-03-01

The placing on the European Union's market of genetically modified crops requires authorization by the European Commission which is based on the proof that the derived foods are as safe as their conventional counterparts. The assessment of potential allergenicity is part of the necessary investigations recommended in the updated Guidance Document of the Scientific Panel on Genetically Modified Organisms (GMO) of the European Food Safety Authority (EFSA), which is based on internationally agreed recommendations. All genetically modified crops which so far have been authorized in the European Union were evaluated by the EFSA GMO Panel which considered it unlikely that their overall allergenicity has been altered.

Oral delivery of dsRNA by microbes: Beyond pest control.

PubMed

Abrieux, Antoine; Chiu, Joanna C

2016-01-01

RNA interference (RNAi) by oral delivery of dsRNA in insects has great potential as a tool for integrated pest management (IPM), especially with respect to addressing the need to reduce off-target effect and slow down resistance development to chemical insecticides. Employing the natural association existing between insect and yeast, we developed a novel method to enable the knock down of vital genes in the pest insect Drosophila suzukii through oral delivery of species-specific dsRNA using genetically modified Saccharomyces cerevisae. D. suzukii that were fed with our "yeast biopesticide" showed a significant decrease in fitness. In this perspective article, we postulate that this approach could be adapted to a large number of species, given the great diversity of symbiotic interactions involving microorganisms and host species. Furthermore, we speculate that beyond its application as biopesticide, dsRNA delivery by genetically modified microbes can also serve to facilitate reverse genetic applications, specifically in non-model organisms.

Human genetic susceptibility and infection with Leishmania peruviana

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

Shaw, M.A.; Davis, C.R.; Collins, A.

1995-11-01

Racial differences, familial clustering, and murine studies are suggestive of host genetic control of Leishmania infections. Complex segregation analysis has been carried out by use of the programs POINTER and COMDS and data from a total population survey, comprising 636 nuclear families, from an L. perurviana endemic area. The data support genetic components controlling susceptibility to clinical leishmaniasis, influencing severity of disease and resistance to disease among healthy individuals. A multifactorial model is favored over a sporadic model. Two-locus models provided the best fit to the data, the optimal model being a recessive gene (frequency .57) plus a modifier locus.more » Individuals infected at an early age and with recurrent lesions are genetically more susceptible than those infected with a single episode of disease at a later age. Among people with no lesions, those with a positive skin-test response are genetically less susceptible than those with a negative response. The possibility of the involvement of more than one gene together with environmental effects has implications for the design of future linkage studies. 31 refs., 7 tabs.« less

Reframed Genome-Scale Metabolic Model to Facilitate Genetic Design and Integration with Expression Data.

PubMed

Gu, Deqing; Jian, Xingxing; Zhang, Cheng; Hua, Qiang

2017-01-01

Genome-scale metabolic network models (GEMs) have played important roles in the design of genetically engineered strains and helped biologists to decipher metabolism. However, due to the complex gene-reaction relationships that exist in model systems, most algorithms have limited capabilities with respect to directly predicting accurate genetic design for metabolic engineering. In particular, methods that predict reaction knockout strategies leading to overproduction are often impractical in terms of gene manipulations. Recently, we proposed a method named logical transformation of model (LTM) to simplify the gene-reaction associations by introducing intermediate pseudo reactions, which makes it possible to generate genetic design. Here, we propose an alternative method to relieve researchers from deciphering complex gene-reactions by adding pseudo gene controlling reactions. In comparison to LTM, this new method introduces fewer pseudo reactions and generates a much smaller model system named as gModel. We showed that gModel allows two seldom reported applications: identification of minimal genomes and design of minimal cell factories within a modified OptKnock framework. In addition, gModel could be used to integrate expression data directly and improve the performance of the E-Fmin method for predicting fluxes. In conclusion, the model transformation procedure will facilitate genetic research based on GEMs, extending their applications.

A design for the control of apoptosis in genetically modified Saccharomyces cerevisiae.

PubMed

Nishida, Nao; Noguchi, Misa; Kuroda, Kouichi; Ueda, Mitsuyoshi

2014-01-01

We have engineered a system that holds potential for use as a safety switch in genetically modified yeasts. Human apoptotic factor BAX (no homolog in yeast), under the control of the FBP1 (gluconeogenesis enzyme) promoter, was conditionally expressed to induce yeast cell apoptosis after glucose depletion. Such systems might prove useful for the safe use of genetically modified organisms.

76 FR 78232 - Monsanto Co.; Determination of Nonregulated Status for Soybean Genetically Engineered To Have a...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... peer review of safety tests, and health effects of genetically modified organisms and glyphosate. APHIS...] Monsanto Co.; Determination of Nonregulated Status for Soybean Genetically Engineered To Have a Modified... that there is reason to believe are plant pests. Such genetically engineered organisms and products are...

Fetal wound healing using a genetically modified murine model: the contribution of P-selectin

USDA-ARS?s Scientific Manuscript database

During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wo...

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

PubMed

Jóri, Balazs; Kamps, Rick; Xanthoulea, Sofia; Delvoux, Bert; Blok, Marinus J; Van de Vijver, Koen K; de Koning, Bart; Oei, Felicia Trups; Tops, Carli M; Speel, Ernst Jm; Kruitwagen, Roy F; Gomez-Garcia, Encarna B; Romano, Andrea

2015-12-01

The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer. A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis. A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype. A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.

Avoiding genetically modified foods in GMO Ground Zero: A reflective self-narrative.

PubMed

Edwards, Sachi

2015-05-01

I engage in a reflective self-narrative of my experience attempting to maintain a diet free of genetically modified organisms. Social tension over the genetically modified organism industry in Hawai'i, United States, has led to public debates over jobs and social identities. Drawing on local media sources, grassroots organizations, and blog posts, I describe the way this tension has shaped my experience with food, eating, and being with others as a genetically modified organism avoider. I utilize discursive positioning to make sense of my experiences by locating them within the ongoing public conversations that give structure to the daily lives of Hawai'i's residents. © The Author(s) 2015.

A Novel Hybrid Classification Model of Genetic Algorithms, Modified k-Nearest Neighbor and Developed Backpropagation Neural Network

PubMed Central

Salari, Nader; Shohaimi, Shamarina; Najafi, Farid; Nallappan, Meenakshii; Karishnarajah, Isthrinayagy

2014-01-01

Among numerous artificial intelligence approaches, k-Nearest Neighbor algorithms, genetic algorithms, and artificial neural networks are considered as the most common and effective methods in classification problems in numerous studies. In the present study, the results of the implementation of a novel hybrid feature selection-classification model using the above mentioned methods are presented. The purpose is benefitting from the synergies obtained from combining these technologies for the development of classification models. Such a combination creates an opportunity to invest in the strength of each algorithm, and is an approach to make up for their deficiencies. To develop proposed model, with the aim of obtaining the best array of features, first, feature ranking techniques such as the Fisher's discriminant ratio and class separability criteria were used to prioritize features. Second, the obtained results that included arrays of the top-ranked features were used as the initial population of a genetic algorithm to produce optimum arrays of features. Third, using a modified k-Nearest Neighbor method as well as an improved method of backpropagation neural networks, the classification process was advanced based on optimum arrays of the features selected by genetic algorithms. The performance of the proposed model was compared with thirteen well-known classification models based on seven datasets. Furthermore, the statistical analysis was performed using the Friedman test followed by post-hoc tests. The experimental findings indicated that the novel proposed hybrid model resulted in significantly better classification performance compared with all 13 classification methods. Finally, the performance results of the proposed model was benchmarked against the best ones reported as the state-of-the-art classifiers in terms of classification accuracy for the same data sets. The substantial findings of the comprehensive comparative study revealed that performance of the proposed model in terms of classification accuracy is desirable, promising, and competitive to the existing state-of-the-art classification models. PMID:25419659

How scary! An analysis of visual communication concerning genetically modified organisms in Italy.

PubMed

Ventura, Vera; Frisio, Dario G; Ferrazzi, Giovanni; Siletti, Elena

2017-07-01

Several studies provide evidence of the role of written communication in influencing public perception towards genetically modified organisms, whereas visual communication has been sparsely investigated. This article aims to evaluate the exposure of the Italian population to scary genetically modified organism-related images. A set of 517 images collected through Google are classified considering fearful attributes, and an index that accounts for the scary impact of these images is built. Then, through an ordinary least-squares regression, we estimate the relationship between the Scary Impact Index and a set of variables that describes the context in which the images appear. The results reveal that the first (and most viewed) Google result images contain the most frightful contents. In addition, the agri-food sector in Italy is strongly oriented towards offering a negative representation of genetically modified organisms. Exposure to scary images could be a factor that affects the negative perception of genetically modified organisms in Italy.

Farmers' valuation of incentives to produce genetically modified organism-free milk: Insights from a discrete choice experiment in Germany.

PubMed

Schreiner, J A; Latacz-Lohmann, U

2015-11-01

This paper investigates farmers' willingness to participate in a genetically modified organism (GMO)-free milk production scheme offered by some German dairy companies. The empirical analysis is based upon discrete choice experiments with 151 dairy farmers from 2 regions in Germany. A conditional logit estimation reveals a strong positive effect of the price premium on offer. Reliable feed monitoring and free technical support increase the likelihood of scheme adoption, the latter however only in farms that have been receiving technical support in other fields. By contrast, any interference with the entrepreneurial autonomy of farmers, through pre-arranged feed procurement or prescriptive advice on the part of the dairy company, lowers acceptance probabilities. Farmers' attitudes toward cultivation of genetically modified soy, their assessment of the market potential of GMO-free milk and future feed prices were found to be significant determinants of adoption, as are farmer age, educational status, and current feeding regimens. Respondents requested on average a mark-up of 0.80 eurocents per kilogram of milk to accept a contract. Comparison of the estimates for the 2 regions suggests that farmers in northern Germany are, on average, more likely to convert to genetically modified-free production; however, farmers in the south are, ceteris paribus, more responsive to an increase in the price premium offered. A latent class model reveals significant differences in the valuation of scheme attributes between 2 latent classes of adopters and nonadopters. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Possibilities for the evolution of the genetic code from a preceding form

NASA Technical Reports Server (NTRS)

Jukes, T. H.

1973-01-01

Analysis of the interaction between mRNA codons and tRNA anticodons suggests a model for the evolution of the genetic code. Modification of the nucleic acid following the anticodon is at present essential in both eukaryotes and prokaryotes to ensure fidelity of translation of codons starting with A, and the amino acids which could be coded for before the evolution of the modifying enzymes can be deduced.

[Methods of identification and assessment of safety of genetically modified microorganisms in manufacture food production].

PubMed

Khovaev, A A; Nesterenko, L N; Naroditskiĭ, B S

2011-01-01

Methods of identification of genetically modified microorganisms (GMM), used in manufacture food on control probes are presented. Results of microbiological and molecular and genetic analyses of food products and their components important in microbiological and genetic expert examination of GMM in foods are considered. Examination of biosafety of GMM are indicated.

Identification of Mom12 and Mom13, two novel modifier loci of Apc (Min) -mediated intestinal tumorigenesis.

PubMed

Crist, Richard C; Roth, Jacquelyn J; Lisanti, Michael P; Siracusa, Linda D; Buchberg, Arthur M

2011-04-01

Colorectal cancer is a heterogeneous disease resulting from a combination of genetic and environmental factors. The C57BL/6J (B6) Apc (Min/+) mouse develops polyps throughout the gastrointestinal tract and has been a valuable model for understanding the genetic basis of intestinal tumorigenesis. Apc (Min/+) mice have been used to study known oncogenes and tumor suppressor genes on a controlled genetic background. These studies often utilize congenic knockout alleles, which can carry an unknown amount of residual donor DNA. The Apc (Min) model has also been used to identify modifer loci, known as Modifier of Min (Mom) loci, which alter Apc (Min) -mediated intestinal tumorigenesis. B6 mice carrying a knockout allele generated in WW6 embryonic stem cells were crossed to B6 Apc (Min/+) mice to determine the effect on polyp multiplicity. The newly generated colony developed significantly more intestinal polyps than Apc (Min/+) controls. Polyp multiplicity did not correlate with inheritance of the knockout allele, suggesting the presence of one or more modifier loci segregating in the colony. Genotyping of simple sequence length polymorphism (SSLP) markers revealed residual 129X1/SvJ genomic DNA within the congenic region of the parental knockout line. An analysis of polyp multiplicity data and SSLP genotyping indicated the presence of two Mom loci in the colony: 1) Mom12, a dominant modifier linked to the congenic region on chromosome 6, and 2) Mom13, which is unlinked to the congenic region and whose effect is masked by Mom12. The identification of Mom12 and Mom13 demonstrates the potential problems resulting from residual heterozygosity present in congenic lines.

Adoptive immunotherapy using PRAME-specific T cells in medulloblastoma.

PubMed

Orlando, Domenico; Miele, Evelina; De Angelis, Biagio; Guercio, Marika; Boffa, Iolanda; Sinibaldi, Matilde; Po, Agnese; Caruana, Ignazio; Abballe, Luana; Carai, Andrea; Caruso, Simona; Camera, Antonio; Moseley, Annemarie; Hagedoorn, Renate S; Heemskerk, Mirjam H M; Giangaspero, Felice; Mastronuzzi, Angela; Ferretti, Elisabetta; Locatelli, Franco; Quintarelli, Concetta

2018-04-03

Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity. Identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated the expression of the tumor-associated antigen PRAME in biopsies from 60 medulloblastoma patients. PRAME expression was detectable in 82% of tissues independent of molecular and histopathologic subgroups. High PRAME expression also correlated with worse overall survival. We next investigated the relevance of PRAME as a target for immunotherapy. Medulloblastoma cells were targeted using genetically modified T cells with a PRAME-specific TCR (SLL TCR T cells). SLL TCR T cells efficiently killed medulloblastoma HLA-A*02+ DAOY cells as well as primary HLA-A*02+ medulloblastoma cells. Moreover, SLL TCR T cells controlled tumor growth in an orthotopic mouse model of medulloblastoma. To prevent unexpected T cell-related toxicity,an inducible caspase 9 (iC9) gene was introduced in frame with the SLL TCR; this safety switch triggered prompt elimination of genetically-modified T cells. Altogether, these data indicate that T cells genetically modified with a high-affinity, PRAME-specific TCR and iC9 may represent a promising innovative approach for treating HLA-A*02+ medulloblastoma patients. Copyright ©2018, American Association for Cancer Research.

Model studies on the detectability of genetically modified feeds in milk.

PubMed

Poms, R E; Hochsteiner, W; Luger, K; Glössl, J; Foissy, H

2003-02-01

Detecting the use of genetically modified feeds in milk has become important, because the voluntary labeling of milk and dairy products as "GMO free" or as "organically grown" prohibits the employment of genetically modified organisms (GMOs). The aim of this work was to investigate whether a DNA transfer from foodstuffs like soya and maize was analytically detectable in cow's milk after digestion and transportation via the bloodstream of dairy cows and, thus, whether milk could report for the employment of transgene feeds. Blood, milk, urine, and feces of dairy cows were examined, and foreign DNA was detected by polymerase chain reaction by specifically amplifying a 226-bp fragment of the maize invertase gene and a 118-bp fragment of the soya lectin gene. An intravenous application of purified plant DNA showed a fast elimination of marker DNA in blood or its reduction below the detection limit. With feeding experiments, it could be demonstrated that a specific DNA transfer from feeds into milk was not detectable. Therefore, foreign DNA in milk cannot serve as an indicator for the employment of transgene feeds unless milk is directly contaminated with feed components or airborne feed particles.

BATS AND BT INSECT RESISTANCE ON AGRICULTURAL LANDSCAPES

EPA Science Inventory

A landscape model that utilizes land cover classification data, insect life history, insect movement, and bat foraging pressure is developed that addresses the implementation of genetically modified crops in the Winter Garden region of Texas. The principal strategy for delaying r...

Readiness of adolescents to use genetically modified organisms according to their knowledge and emotional attitude towards GMOs.

PubMed

Lachowski, Stanisław; Jurkiewicz, Anna; Choina, Piotr; Florek-Łuszczki, Magdalena; Buczaj, Agnieszka; Goździewska, Małgorzata

2017-06-07

Agriculture based on genetically modified organisms plays an increasingly important role in feeding the world population, which is evidenced by a considerable growth in the size of land under genetically modified crops (GM). Uncertainty and controversy around GM products are mainly due to the lack of accurate and reliable information, and lack of knowledge concerning the essence of genetic modifications, and the effect of GM food on the human organism, and consequently, a negative emotional attitude towards what is unknown. The objective of the presented study was to discover to what extent knowledge and the emotional attitude of adolescents towards genetically modified organisms is related with acceptance of growing genetically modified plants or breeding GM animals on own farm or allotment garden, and the purchase and consumption of GM food, as well as the use of GMOs in medicine. The study was conducted by the method of a diagnostic survey using a questionnaire designed by the author, which covered a group of 500 adolescents completing secondary school on the level of maturity examination. The collected material was subjected to statistical analysis. Research hypotheses were verified using chi-square test (χ ² ), t-Student test, and stepwise regression analysis. Stepwise regression analysis showed that the readiness of adolescents to use genetically modified organisms as food or for the production of pharmaceuticals, the production of GM plants or animals on own farm, depends on an emotional-evaluative attitude towards GMOs, and the level of knowledge concerning the essence of genetic modifications.

Survival of Skin Graft between Transgenic Cloned Dogs and Non-Transgenic Cloned Dogs

PubMed Central

Kim, Geon A; Oh, Hyun Ju; Kim, Min Jung; Jo, Young Kwang; Choi, Jin; Park, Jung Eun; Park, Eun Jung; Lim, Sang Hyun; Yoon, Byung Il; Kang, Sung Keun; Jang, Goo; Lee, Byeong Chun

2014-01-01

Whereas it has been assumed that genetically modified tissues or cells derived from somatic cell nuclear transfer (SCNT) should be accepted by a host of the same species, their immune compatibility has not been extensively explored. To identify acceptance of SCNT-derived cells or tissues, skin grafts were performed between cloned dogs that were identical except for their mitochondrial DNA (mtDNA) haplotypes and foreign gene. We showed here that differences in mtDNA haplotypes and genetic modification did not elicit immune responses in these dogs: 1) skin tissues from genetically-modified cloned dogs were successfully transplanted into genetically-modified cloned dogs with different mtDNA haplotype under three successive grafts over 63 days; and 2) non-transgenic cloned tissues were accepted into transgenic cloned syngeneic recipients with different mtDNA haplotypes and vice versa under two successive grafts over 63 days. In addition, expression of the inserted gene was maintained, being functional without eliciting graft rejection. In conclusion, these results show that transplanting genetically-modified tissues into normal, syngeneic or genetically-modified recipient dogs with different mtDNA haplotypes do not elicit skin graft rejection or affect expression of the inserted gene. Therefore, therapeutically valuable tissue derived from SCNT with genetic modification might be used safely in clinical applications for patients with diseased tissues. PMID:25372489

40 CFR 172.45 - Requirement for a notification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... EXPERIMENTAL USE PERMITS Notification for Certain Genetically Modified Microbial Pesticides § 172.45... modified. (2) Nonindigenous microbial pesticides that have not been acted upon by the U.S. Department of... introduction of genetic material that has been deliberately modified. (ii) [Reserved] (2) Testing conducted in...

A Simulation Study of Mutations in the Genetic Regulatory Hierarchy for Butterfly Eyespot Focus Determination

PubMed Central

Marcus, Jeffrey M.; Evans, Travis M.

2008-01-01

The color patterns on the wings of butterflies have been an important model system in evolutionary developmental biology. A recent computational model tested genetic regulatory hierarchies hypothesized to underlie the formation of butterfly eyespot foci (Evans and Marcus, 2006). The computational model demonstrated that one proposed hierarchy was incapable of reproducing the known patterns of gene expression associated with eyespot focus determination in wild-type butterflies, but that two slightly modified alternative hierarchies were capable of reproducing all of the known gene expressions patterns. Here we extend the computational models previously implemented in Delphi 2.0 to two mutants derived from the squinting bush brown butterfly (Bicyclus anynana). These two mutants, comet and Cyclops, have aberrantly shaped eyespot foci that are produced by different mechanisms. The comet mutation appears to produce a modified interaction between the wing margin and the eyespot focus that results in a series of comet-shaped eyespot foci. The Cyclops mutation causes the failure of wing vein formation between two adjacent wing-cells and the fusion of two adjacent eyespot foci to form a single large elongated focus in their place. The computational approach to modeling pattern formation in these mutants allows us to make predictions about patterns of gene expression, which are largely unstudied in butterfly mutants. It also suggests a critical experiment that will allow us to distinguish between two hypothesized genetic regulatory hierarchies that may underlie all butterfly eyespot foci. PMID:18586070

Development of a colloidal gold immunochromatographic strip assay for simple and fast detection of human α-lactalbumin in genetically modified cow milk.

PubMed

Tao, Chenyu; Zhang, Qingde; Feng, Na; Shi, Deshi; Liu, Bang

2016-03-01

The qualitative and quantitative declaration of food ingredients is important to consumers, especially for genetically modified food as it experiences a rapid increase in sales. In this study, we designed an accurate and rapid detection system using colloidal gold immunochromatographic strip assay (GICA) methods to detect genetically modified cow milk. First, we prepared 2 monoclonal antibodies for human α-lactalbumin (α-LA) and measured their antibody titers; the one with the higher titer was used for further experiments. Then, we found the optimal pH value and protein amount of GICA for detection of pure milk samples. The developed strips successfully detected genetically modified cow milk and non-modified cow milk. To determine the sensitivity of GICA, a quantitative ELISA system was used to determine the exact amount of α-LA, and then genetically modified milk was diluted at different rates to test the sensitivity of GICA; the sensitivity was 10 μg/mL. Our results demonstrated that the applied method was effective to detect human α-LA in cow milk. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The use of genetically modified mice in cancer risk assessment: challenges and limitations.

PubMed

Eastmond, David A; Vulimiri, Suryanarayana V; French, John E; Sonawane, Babasaheb

2013-09-01

The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53⁺/⁻, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program's conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals.

The use of genetically modified mice in cancer risk assessment: Challenges and limitations*

PubMed Central

Eastmond, David A.; Vulimiri, Suryanarayana V.; French, John E.; Sonawane, Babasaheb

2015-01-01

The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53+/−, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program’s conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals. PMID:23985072

Emotional attitudes of young people completing secondary schools towards genetic modification of organisms (GMO) and genetically modified foods (GMF).

PubMed

Jurkiewicz, Anna; Zagórski, Jerzy; Bujak, Franciszek; Lachowski, Stanisław; Florek-Łuszczki, Magdalena

2014-01-01

The objective of the study was recognition of the opinions of adolescents completing secondary schools concerning genetically modified organisms and genetically modified food, especially the respondents' emotional attitude towards scientific achievements in the area of live genetically modified organisms. The study covered a group of 500 school adolescents completing secondary school at the level of maturity examination. The study was conducted by the method of a diagnostic survey using a self-designed questionnaire form. Knowledge concerning the possible health effects of consumption of food containing GMO among adolescents competing secondary schools is on a relatively low level; the adolescents examined 'know rather little' or 'very little know' about this problem. In respondents' opinions the results of reliable studies pertaining to the health effects of consumption of GMO 'rather do not exist'. The respondents are against the cultivation of GM plants and breeding of GM animals on own farm in the future. Secondary school adolescents considered that the production of genetically modified food means primarily the enrichment of biotechnological companies, higher income for food producers, and not the elimination of hunger in the world or elimination of many diseases haunting humans.

[Safety assessment of foods derived from genetically modified plants].

PubMed

Pöting, A; Schauzu, M

2010-06-01

The placing of genetically modified plants and derived food on the market falls under Regulation (EC) No. 1829/2003. According to this regulation, applicants need to perform a safety assessment according to the Guidance Document of the Scientific Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA), which is based on internationally agreed recommendations. This article gives an overview of the underlying legislation as well as the strategy and scientific criteria for the safety assessment, which should generally be based on the concept of substantial equivalence and carried out in relation to an unmodified conventional counterpart. Besides the intended genetic modification, potential unintended changes also have to be assessed with regard to potential adverse effects for the consumer. All genetically modified plants and derived food products, which have been evaluated by EFSA so far, were considered to be as safe as products derived from the respective conventional plants.

Contribution of European research to risk analysis.

PubMed

Boenke, A

2001-12-01

The European Commission's, Quality of Life Research Programme, Key Action 1-Health, Food & Nutrition is mission-oriented and aims, amongst other things, at providing a healthy, safe and high-quality food supply leading to reinforced consumer confidence in the safety, of European food. Its objectives also include the enhancing of the competitiveness of the European food supply. Key Action 1 is currently supporting a number of different types of European collaborative projects in the area of risk analysis. The objectives of these projects range from the development and validation of prevention strategies including the reduction of consumers risks; development and validation of new modelling approaches, harmonization of risk assessment principles methodologies and terminology; standardization of methods and systems used for the safety evaluation of transgenic food; providing of tools for the evaluation of human viral contamination of shellfish and quality control; new methodologies for assessing the potential of unintended effects of genetically modified (genetically modified) foods; development of a risk assessment model for Cryptosporidium parvum related to the food and water industries, to the development of a communication platform for genetically modified organism, producers, retailers, regulatory authorities and consumer groups to improve safety assessment procedures, risk management strategies and risk communication; development and validation of new methods for safety testing of transgenic food; evaluation of the safety and efficacy of iron supplementation in pregnant women, evaluation of the potential cancer-preventing activity of pro- and pre-biotic ('synbiotic') combinations in human volunteers. An overview of these projects is presented here.

[From stone-craved genes to Michelangelo: significance and different aspects of gene-environment interaction].

PubMed

Lazary, Judit

2017-12-01

Although genetic studies have improved a lot in recent years, without clinical relevance sometimes their significance is devalued. Reviewing the major milestones of psychogenomics it can be seen that break-through success is just a question of time. Investigations of direct effect of genetic variants on phenotypes have not yielded positive findings. However, an important step was taken by adapting the gene-environment interaction model. In this model genetic vulnerability stepped into the place of "stone craved" pathology. Further progress happened when studies of environmental factors were combined with genetic function (epigenetics). This model provided the possibility for investigation of therapeutic interventions as environmental factors and it was proven that effective treatments exert a modifying effect on gene expression. Moreover, recent developments focus on therapeutic manipulation of gene function (e.g. chemogenetics). Instead of "stone craved" genes up-to-date dynamically interacting gene function became the basis of psychogenomics in which correction of the expression is a potential therapeutic tool. Keeping in mind these trends and developments, there is no doubt that genetics will be a fundamental part of daily clinical routine in the future.

Not all GMOs are crop plants: non-plant GMO applications in agriculture

USDA-ARS?s Scientific Manuscript database

In the time since the tools of modern biotechnology have become available, the most commonly applied and often discussed genetically modified organisms are genetically modified crop plants, although genetic engineering is also being used successfully in organisms other than plants, including bacteri...

Resistance Management Research Status

EPA Science Inventory

Long-term sustainability of genetically modified corn expressing Bt relies on the validity of assumptions underlying IRM models used by the EPA and the ability of EPA to monitor, detect and react to insect resistance when it develops. The EPA is developing a multi-tiered approac...

A subset of skin tumor modifier loci determines survival time of tumor-bearing mice

PubMed Central

Nagase, Hiroki; Mao, Jian-Hua; Balmain, Allan

1999-01-01

Studies of mouse models of human cancer have established the existence of multiple tumor modifiers that influence parameters of cancer susceptibility such as tumor multiplicity, tumor size, or the probability of malignant progression. We have carried out an analysis of skin tumor susceptibility in interspecific Mus musculus/Mus spretus hybrid mice and have identified another seven loci showing either significant (six loci) or suggestive (one locus) linkage to tumor susceptibility or resistance. A specific search was carried out for skin tumor modifier loci associated with time of survival after development of a malignant tumor. A combination of resistance alleles at three markers [D6Mit15 (Skts12), D7Mit12 (Skts2), and D17Mit7 (Skts10)], all of which are close to or the same as loci associated with carcinoma incidence and/or papilloma multiplicity, is significantly associated with increased survival of mice with carcinomas, whereas the reverse combination of susceptibility alleles is significantly linked to early mortality caused by rapid carcinoma growth (χ2 = 25.22; P = 5.1 × 10−8). These data indicate that host genetic factors may be used to predict carcinoma growth rate and/or survival of individual backcross mice exposed to the same carcinogenic stimulus and suggest that mouse models may provide an approach to the identification of genetic modifiers of cancer survival in humans. PMID:10611333

Identification of Associations Between Genetic Factors and Asthma that are Modified by Obesity

DTIC Science & Technology

2016-06-01

AFRL-SA-WP-TR-2016-0010 Identification of Associations Between Genetic Factors and Asthma That Are Modified by Obesity Andrew T...Between Genetic Factors and Asthma That Are Modified by Obesity 5a. CONTRACT NUMBER FA8650-13-2-6371 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...among African American women in the Women’s Health Initiative study. 15. SUBJECT TERMS Body mass index, SNP, asthma, obesity , genome, genes 16

Unscented Sampling Techniques For Evolutionary Computation With Applications To Astrodynamic Optimization

DTIC Science & Technology

2016-09-01

to both genetic algorithms and evolution strategies to achieve these goals. The results of this research offer a promising new set of modified ...abs_all.jsp?arnumber=203904 [163] Z. Michalewicz, C. Z. Janikow, and J. B. Krawczyk, “A modified genetic algo- rithm for optimal control problems...Available: http://arc.aiaa.org/doi/abs/10.2514/ 2.7053 375 [166] N. Yokoyama and S. Suzuki, “ Modified genetic algorithm for constrained trajectory

[Impacts of genetically modified soybean leaf residues on Folsomia candida.

PubMed

Zhou, Lin; Wang, Bai Feng; Liu, Xin Ying; Jiang, Ying; Wang, Da Ming; Feng, Shu Dan; Song, Xin Yuan

2016-09-01

When the genetically modified soybean is planted in the field, the expression product of exogenous gene could be exposed in the soil ecosystem and bring potential risk to the soil fauna, with the form of leaves and other debris. A few of genetically modified soybeans developed by China independently were used in our study as materials. They were Phytophthora-resistant soybean harboring hrpZm gene (B4J8049), leaf-feeding insect-resistant soybean harboring Cry1C gene (A2A8001) and Leguminivora glycinivorella-resistant soybean harboring Cry1Iem gene (C802). By feeding Folsomia candida with the three genetically modified soybeans for continuous 60 days, the surviving rate, reproductive rate and changes on the body length of F. candida were studied. The results showed that all the three genetically modified soybeans of B4J8049, A2A8001 and C802 had no significant adverse effects on the growth of F. candida, as an environmental indicator organism. It was initially inferred that they were environmentally safe under short-term exposure, which provided basic data of ecological safety for their wide cultivation.

Genetic basis and detection of unintended effects in genetically modified crop plants

USDA-ARS?s Scientific Manuscript database

In January 2014, an international meeting sponsored by the International Life Sciences Institute/Health and Environmental Sciences Institute and the Canadian Food Inspection Agency titled “Genetic Basis of Unintended Effects in Modified Plants” was held in Ottawa, Canada, bringing together over 75 s...

76 FR 37771 - Monsanto Co.; Availability of Petition, Plant Pest Risk Assessment, and Environmental Assessment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

... Determination of Nonregulated Status for Soybean Genetically Engineered To Have a Modified Fatty Acid Profile... soybean designated as MON 87705, which has been genetically engineered to have a modified fatty acid... our regulations concerning the introduction of certain genetically engineered organisms and products...

Progress and Prospects for Genetic Modification of Nonhuman Primate Models in Biomedical Research

PubMed Central

Chan, Anthony W. S.

2013-01-01

The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model. PMID:24174443

Safety and Efficacy of OXB-202, a Genetically Engineered Tissue Therapy for the Prevention of Rejection in High-Risk Corneal Transplant Patients.

PubMed

Fouladi, Naghmeh; Parker, Maria; Kennedy, Vicky; Binley, Katie; McCloskey, Laura; Loader, Julie; Kelleher, Michelle; Mitrophanous, Kyriacos A; Stout, J Timothy; Ellis, Scott

2018-06-01

Due to both the avascularity of the cornea and the relatively immune-privileged status of the eye, corneal transplantation is one of the most successful clinical transplant procedures. However, in high-risk patients, which account for >20% of the 180,000 transplants carried out worldwide each year, the rejection rate is high due to vascularization of the recipient cornea. The main reason for graft failure is irreversible immunological rejection, and it is therefore unsurprising that neovascularization (NV; both pre and post grafting) is a significant risk factor for subsequent graft failure. NV is thus an attractive target to prevent corneal graft rejection. OXB-202 (previously known as EncorStat ® ) is a donor cornea modified prior to transplant by ex vivo genetic modification with genes encoding secretable forms of the angiostatic human proteins, endostatin and angiostatin. This is achieved using a lentiviral vector derived from the equine infectious anemia virus called pONYK1EiA, which subsequently prevents rejection by suppressing NV. Previously, it has been shown that rabbit donor corneas treated with pONYK1EiA substantially suppress corneal NV, opacity, and subsequent rejection in an aggressive rabbit model of cornea graft rejection. Here, efficacy data are presented in a second rabbit model, which more closely mirrors the clinical setting for high-risk corneal transplant patients, and safety data from a 3-month good laboratory practice toxicology and biodistribution study of pONYK1EiA-modified rabbit corneas in a rabbit corneal transplant model. It is shown that pONYK1EiA-modified rabbit corneas (OXB-202) significantly reduce corneal NV and the rate of corneal rejection in a dose-dependent fashion, and are tolerated with no adverse toxicological findings or significant biodistribution up to 13 weeks post surgery in these rabbit studies. In conclusion, angiogenesis is a valid target to prevent corneal graft rejection in a high-risk setting, and transplanted genetically modified corneas are safe and well-tolerated in an animal model. These data support the evaluation of OXB-202 in a first-in-human trial.

Genetic association studies in β-hemoglobinopathies.

PubMed

Thein, Swee Lay

2013-01-01

Characterization of the molecular basis of the β-thalassemias and sickle cell disease (SCD) clearly showed that individuals with the same β-globin genotypes can have extremely diverse clinical severity. Two key modifiers, an innate ability to produce fetal hemoglobin and coinheritance of α-thalassemia, both derived from family and population studies, affect the pathophysiology of both disorders at the primary level. In the past 2 decades, scientific research had applied genetic approaches to identify additional genetic modifiers. The review summarizes recent genetic studies and key genetic modifiers identified and traces the story of fetal hemoglobin genetics, which has led to an emerging network of globin gene regulation. The discoveries have provided insights on new targets for therapeutic intervention and raise possibilities of developing fetal hemoglobin predictive diagnostics for predicting disease severity in the newborn and for integration into prenatal diagnosis to better inform genetic counseling.

A Modified Penalty Parameter Approach for Optimal Estimation of UH with Simultaneous Estimation of Infiltration Parameters

NASA Astrophysics Data System (ADS)

Bhattacharjya, Rajib Kumar

2018-05-01

The unit hydrograph and the infiltration parameters of a watershed can be obtained from observed rainfall-runoff data by using inverse optimization technique. This is a two-stage optimization problem. In the first stage, the infiltration parameters are obtained and the unit hydrograph ordinates are estimated in the second stage. In order to combine this two-stage method into a single stage one, a modified penalty parameter approach is proposed for converting the constrained optimization problem to an unconstrained one. The proposed approach is designed in such a way that the model initially obtains the infiltration parameters and then searches the optimal unit hydrograph ordinates. The optimization model is solved using Genetic Algorithms. A reduction factor is used in the penalty parameter approach so that the obtained optimal infiltration parameters are not destroyed during subsequent generation of genetic algorithms, required for searching optimal unit hydrograph ordinates. The performance of the proposed methodology is evaluated by using two example problems. The evaluation shows that the model is superior, simple in concept and also has the potential for field application.

Analysis of genetically modified organisms by pyrosequencing on a portable photodiode-based bioluminescence sequencer.

PubMed

Song, Qinxin; Wei, Guijiang; Zhou, Guohua

2014-07-01

A portable bioluminescence analyser for detecting the DNA sequence of genetically modified organisms (GMOs) was developed by using a photodiode (PD) array. Pyrosequencing on eight genes (zSSIIb, Bt11 and Bt176 gene of genetically modified maize; Lectin, 35S-CTP4, CP4EPSPS, CaMV35S promoter and NOS terminator of the genetically modified Roundup ready soya) was successfully detected with this instrument. The corresponding limit of detection (LOD) was 0.01% with 35 PCR cycles. The maize and soya available from three different provenances in China were detected. The results indicate that pyrosequencing using the small size of the detector is a simple, inexpensive, and reliable way in a farm/field test of GMO analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

A review of standardized metabolic phenotyping of animal models.

PubMed

Rozman, Jan; Klingenspor, Martin; Hrabě de Angelis, Martin

2014-10-01

Metabolic phenotyping of genetically modified animals aims to detect new candidate genes and related metabolic pathways that result in dysfunctional energy balance regulation and predispose for diseases such as obesity or type 2 diabetes mellitus. In this review, we provide a comprehensive overview on the technologies available to monitor energy flux (food uptake, bomb calorimetry of feces and food, and indirect calorimetry) and body composition (qNMR, DXA, and MRI) in animal models for human diseases with a special focus on phenotyping methods established in genetically engineered mice. We use an energy flux model to illustrate the principles of energy allocation, describe methodological aspects how to monitor energy balance, and introduce strategies for data analysis and presentation.

Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases.

PubMed

Haney, Matthew J; Zhao, Yuling; Harrison, Emily B; Mahajan, Vivek; Ahmed, Shaheen; He, Zhijian; Suresh, Poornima; Hingtgen, Shawn D; Klyachko, Natalia L; Mosley, R Lee; Gendelman, Howard E; Kabanov, Alexander V; Batrakova, Elena V

2013-01-01

The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA) encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD). This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders.

Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases

PubMed Central

Haney, Matthew J.; Zhao, Yuling; Harrison, Emily B.; Mahajan, Vivek; Ahmed, Shaheen; He, Zhijian; Suresh, Poornima; Hingtgen, Shawn D.; Klyachko, Natalia L.; Mosley, R. Lee; Gendelman, Howard E.; Kabanov, Alexander V.; Batrakova, Elena V.

2013-01-01

The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA) encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD). This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders. PMID:23620794

Safety assessment, detection and traceability, and societal aspects of genetically modified foods. European Network on Safety Assessment of Genetically Modified Food Crops (ENTRANSFOOD). Concluding remarks.

PubMed

Kuiper, H A; König, A; Kleter, G A; Hammes, W P; Knudsen, I

2004-07-01

The most important results from the EU-sponsored ENTRANSFOOD Thematic Network project are reviewed, including the design of a detailed step-wise procedure for the risk assessment of foods derived from genetically modified crops based on the latest scientific developments, evaluation of topical risk assessment issues, and the formulation of proposals for improved risk management and public involvement in the risk analysis process. Copyright 2004 Elsevier Ltd.

Identification of Transgenic Organisms Based on Terahertz Spectroscopy and Hyper Sausage Neuron

NASA Astrophysics Data System (ADS)

Liu, J.; Li, Zh.; Hu, F.; Chen, T.; Du, Y.; Xin, H.

2015-03-01

This paper presents a novel approach for identifi cation of terahertz (THz) spectra of genetically modifi ed organisms (GMOs) based on hyper sausage neuron (HSN), and THz transmittance spectra of some typical transgenic sugarbeet samples are investigated to demonstrate its feasibility. Principal component analysis (PCA) is applied to extract features of the spectrum data, and instead of the original spectrum data, the feature signals are fed into the HSN pattern recognition, a new multiple weights neural network (MWNN). The experimental result shows that the HSN model not only can correctly classify different types of transgenic sugar-beets, but also can reject nonsimilar samples of the same type. The proposed approach provides a new effective method for detection and identification of genetically modified organisms by using THz spectroscopy.

Resistance Management Research Status-May 2008

EPA Science Inventory

Long-term sustainability of genetically modified corn expressing Bt relies on the validity of assumptions underlying IRM models used by the EPA and the ability of EPA to monitor, detect and react to insect resistance when it develops. The EPA is developing a multi-tiered approac...

Autism-related neuroligin-3 mutation alters social behavior and spatial learning.

PubMed

Jaramillo, Thomas C; Liu, Shunan; Pettersen, Ami; Birnbaum, Shari G; Powell, Craig M

2014-04-01

Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Südhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Südhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore, we sought to replicate our findings in the neuroligin-3 R451C point mutant knock-in mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social deficits, enhanced spatial learning, and increased locomotor activity. These data extend our previous findings that NL3R451C mice exhibit autism-relevant behavioral abnormalities and further suggest that different genetic backgrounds can modify this behavioral phenotype through epistatic genetic interactions. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Clinical potential and challenges of using genetically modified cells for articular cartilage repair.

PubMed

Madry, Henning; Cucchiarini, Magali

2011-06-01

Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration.

Genetic Modifiers of Sickle Cell Disease

PubMed Central

Steinberg, Martin H.; Sebastiani, Paola

2015-01-01

Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident ∝ thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new “druggable” pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease. PMID:22641398

Modifying Knowledge, Emotions, and Attitudes Regarding Genetically Modified Foods

ERIC Educational Resources Information Center

Heddy, Benjamin C.; Danielson, Robert W.; Sinatra, Gale M.; Graham, Jesse

2017-01-01

The purpose of this study was to explore whether conceptual change predicted emotional and attitudinal change while learning about genetically modified foods (GMFs). Participants were 322 college students; half read a refutation text designed to shift conceptual knowledge, emotions, and attitudes, while the other half served as a control group.…

Modifier genes in Mendelian disorders: the example of cystic fibrosis

PubMed Central

Cutting, Garry R.

2011-01-01

In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention. PMID:21175684

ASSESSING POSSIBLE ECOLOGICAL RISKS OF GENETICALLY MODIFIED CROPS: GENE EXPRESSION ASSAYS AND GENETIC MONITORING OF NON-TARGET ORGANISMS

EPA Science Inventory

Widespread planting of genetically modified crops with the Bt transgene pesticide has led to concern over non-target effects of Bt compounds in agroecosystems. While some research suggests that non-target organisms exposed to Bt toxin exhibit reduced fecundity and increased morta...

Genetically modified yeast species, and fermentation processes using genetically modified yeast

DOEpatents

Rajgarhia, Vineet [Kingsport, TN; Koivuranta, Kari [Helsinki, FI; Penttila, Merja [Helsinki, FI; Ilmen, Marja [Helsinki, FI; Suominen, Pirkko [Maple Grove, MN; Aristidou, Aristos [Maple Grove, MN; Miller, Christopher Kenneth [Cottage Grove, MN; Olson, Stacey [St. Bonifacius, MN; Ruohonen, Laura [Helsinki, FI

2014-01-07

Yeast cells are transformed with an exogenous xylose isomerase gene. Additional genetic modifications enhance the ability of the transformed cells to ferment xylose to ethanol or other desired fermentation products. Those modifications include deletion of non-specific aldose reductase gene(s), deletion of xylitol dehydrogenase gene(s) and/or overexpression of xylulokinase.

40 CFR 158.2100 - Microbial pesticides definition and applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to which the organism has been genetically modified. (4) Pest control organisms such as insect... and supported by data required in this subpart. (3) Genetically modified microbial pesticides may be...

Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington’s Disease Knock-In Mice

PubMed Central

Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R.; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C.; Pinto, Ricardo Mouro

2017-01-01

Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. PMID:27913616

Workshop overview: approaches to the assessment of the allergenic potential of food from genetically modified crops.

PubMed

Ladics, Gregory S; Holsapple, Michael P; Astwood, James D; Kimber, Ian; Knippels, Leon M J; Helm, Ricki M; Dong, Wumin

2003-05-01

There is a need to assess the safety of foods deriving from genetically modified (GM) crops, including the allergenic potential of novel gene products. Presently, there is no single in vitro or in vivo model that has been validated for the identification or characterization of potential food allergens. Instead, the evaluation focuses on risk factors such as source of the gene (i.e., allergenic vs. nonallergenic sources), physicochemical and genetic comparisons to known allergens, and exposure assessments. The purpose of this workshop was to gather together researchers working on various strategies for assessing protein allergenicity: (1) to describe the current state of knowledge and progress that has been made in the development and evaluation of appropriate testing strategies and (2) to identify critical issues that must now be addressed. This overview begins with a consideration of the current issues involved in assessing the allergenicity of GM foods. The second section presents information on in vitro models of digestibility, bioinformatics, and risk assessment in the context of clinical prevention and management of food allergy. Data on rodent models are presented in the next two sections. Finally, nonrodent models for assessing protein allergenicity are discussed. Collectively, these studies indicate that significant progress has been made in developing testing strategies. However, further efforts are needed to evaluate and validate the sensitivity, specificity, and reproducibility of many of these assays for determining the allergenicity potential of GM foods.

Quantifying introgression risk with realistic population genetics.

PubMed

Ghosh, Atiyo; Meirmans, Patrick G; Haccou, Patsy

2012-12-07

Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified crop regulation. Most theoretical introgression studies aimed at such quantification disregard one or more of the most important factors concerning introgression: realistic genetical mechanisms, repeated invasions and stochasticity. In addition, the use of linkage as a risk mitigation strategy has not been studied properly yet with genetic introgression models. Current genetic introgression studies fail to take repeated invasions and demographic stochasticity into account properly, and use incorrect measures of introgression risk that can be manipulated by arbitrary choices. In this study, we present proper methods for risk quantification that overcome these difficulties. We generalize a probabilistic risk measure, the so-called hazard rate of introgression, for application to introgression models with complex genetics and small natural population sizes. We illustrate the method by studying the effects of linkage and recombination on transgene introgression risk at different population sizes.

Quantifying introgression risk with realistic population genetics

PubMed Central

Ghosh, Atiyo; Meirmans, Patrick G.; Haccou, Patsy

2012-01-01

Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified crop regulation. Most theoretical introgression studies aimed at such quantification disregard one or more of the most important factors concerning introgression: realistic genetical mechanisms, repeated invasions and stochasticity. In addition, the use of linkage as a risk mitigation strategy has not been studied properly yet with genetic introgression models. Current genetic introgression studies fail to take repeated invasions and demographic stochasticity into account properly, and use incorrect measures of introgression risk that can be manipulated by arbitrary choices. In this study, we present proper methods for risk quantification that overcome these difficulties. We generalize a probabilistic risk measure, the so-called hazard rate of introgression, for application to introgression models with complex genetics and small natural population sizes. We illustrate the method by studying the effects of linkage and recombination on transgene introgression risk at different population sizes. PMID:23055068

Enhancing Antitumor Efficacy of Chimeric Antigen Receptor T Cells Through Constitutive CD40L Expression

PubMed Central

Curran, Kevin J; Seinstra, Beatrijs A; Nikhamin, Yan; Yeh, Raymond; Usachenko, Yelena; van Leeuwen, Dayenne G; Purdon, Terence; Pegram, Hollie J; Brentjens, Renier J

2015-01-01

Adoptive cell therapy with genetically modified T cells expressing a chimeric antigen receptor (CAR) is a promising therapy for patients with B-cell acute lymphoblastic leukemia. However, CAR-modified T cells (CAR T cells) have mostly failed in patients with solid tumors or low-grade B-cell malignancies including chronic lymphocytic leukemia with bulky lymph node involvement. Herein, we enhance the antitumor efficacy of CAR T cells through the constitutive expression of CD40 ligand (CD40L, CD154). T cells genetically modified to constitutively express CD40L (CD40L-modified T cells) demonstrated increased proliferation and secretion of proinflammatory TH1 cytokines. Further, CD40L-modified T cells augmented the immunogenicity of CD40+ tumor cells by the upregulated surface expression of costimulatory molecules (CD80 and CD86), adhesion molecules (CD54, CD58, and CD70), human leukocyte antigen (HLA) molecules (Class I and HLA-DR), and the Fas-death receptor (CD95). Additionally, CD40L-modified T cells induced maturation and secretion of the proinflammatory cytokine interleukin-12 by monocyte-derived dendritic cells. Finally, tumor-targeted CD19-specific CAR/CD40L T cells exhibited increased cytotoxicity against CD40+ tumors and extended the survival of tumor-bearing mice in a xenotransplant model of CD19+ systemic lymphoma. This preclinical data supports the clinical application of CAR T cells additionally modified to constitutively express CD40L with anticipated enhanced antitumor efficacy. PMID:25582824

Experience with environmental issues in GM crop production and the likely future scenarios.

PubMed

Gaugitsch, Helmut

2002-02-28

In the Cartagena Protocol on Biosafety, standards for risk assessment of genetically modified organisms (GMOs) have been set. The criteria and information basis for the risk assessment of GMOs have been modified by the EU Directive 2001/18/EC. Various approaches to further improve the criteria for environmental risk assessment of GMOs are described in this study. Reports on the ecological impacts of the cultivation of certain non-transgenic crop plants with novel or improved traits as analogy models to transgenic plants showed that the effects of agricultural practice can be at least equally important as the effects of gene transfer and invasiveness, although the latter currently play a major role in risk assessment of transgenic crops. Based on these results the applicability of the methodology of 'Life Cycle Analysis (LCA)' for genetically modified plants in comparison with conventionally bred and organically grown crop plants was evaluated. The methodology was regarded as applicable with some necessary future improvements. In current projects, the assessment of toxicology and allergenicity of GM crops are analysed, and suggestions for standardization are developed. Based on results and recommendations from these efforts there are still the challenges of how to operationalize the precautionary principle and how to take into account ecologically sensitive ecosystems, including centres of origin and centres of genetic diversity.

Tyrosinase is the modifier of retinoschisis in mice.

PubMed

Johnson, Britt A; Cole, Brian S; Geisert, Eldon E; Ikeda, Sakae; Ikeda, Akihiro

2010-12-01

X-linked retinoschisis (XLRS) is a form of macular degeneration with a juvenile onset. This disease is caused by mutations in the retinoschisin (RS1) gene. The major clinical pathologies of this disease include splitting of the retina (schisis) and a loss in synaptic transmission. Human XLRS patients display a broad range in phenotypic severity, even among family members with the same mutation. This variation suggests the existence of genetic modifiers that may contribute to disease severity. Previously, we reported the identification of a modifier locus, named Mor1, which affects severity of schisis in a mouse model of XLRS (the Rs1tmgc1 mouse). Homozygosity for the protective AKR allele of Mor1 restores cell adhesion in Rs1tmgc1 mice. Here, we report our study to identify the Mor1 gene. Through collecting recombinant mice followed by progeny testing, we have localized Mor1 to a 4.4-Mb region on chromosome 7. In this genetic region, the AKR strain is known to carry a mutation in the tyrosinase (Tyr) gene. We observed that the schisis phenotype caused by the Rs1 mutation is rescued by a Tyr mutation in the C57BL/6J genetic background, strongly suggesting that Tyr is the Mor1 gene.

Genetically Modified Plants: Public and Scientific Perceptions

PubMed Central

2013-01-01

The potential of genetically modified plants to meet the requirements of growing population is not being recognized at present. This is a consequence of concerns raised by the public and the critics about their applications and release into the environment. These include effect on human health and environment, biosafety, world trade monopolies, trustworthiness of public institutions, integrity of regulatory agencies, loss of individual choice, and ethics as well as skepticism about the real potential of the genetically modified plants, and so on. Such concerns are enormous and prevalent even today. However, it should be acknowledged that most of them are not specific for genetically modified plants, and the public should not forget that the conventionally bred plants consumed by them are also associated with similar risks where no information about the gene(s) transfer is available. Moreover, most of the concerns are hypothetical and lack scientific background. Though a few concerns are still to be disproved, it is viewed that, with proper management, these genetically modified plants have immense potential for the betterment of mankind. In the present paper, an overview of the raised concerns and wherever possible reasons assigned to explain their intensity or unsuitability are reviewed. PMID:25937981

Evaluation of genetically-improved (glandless) and genetically-modified low-gossypol cottonseed meal as alternative protein sources in the diet of juvenile southern flounder Paralichthys lethostigma reared in a recirculating

USDA-ARS?s Scientific Manuscript database

Cottonseed meal (CSM) proteins from genetically-improved (glandless) seed (GI-CSM, 52.1% crude protein, CP), genetically-modified low-gossypol seed (GMO-CSM, 56.0% CP) and from an untreated regular (glanded) seed (R-CSM 49.9% CP) were evaluated to replace fish meal (FM) protein (59.5% CP) in juvenil...

Testing for Genetically Modified Foods Using PCR

ERIC Educational Resources Information Center

Taylor, Ann; Sajan, Samin

2005-01-01

The polymerase chain reaction (PCR) is a Nobel Prize-winning technique that amplifies a specific segment of DNA and is commonly used to test for the presence of genetic modifications. Students use PCR to test corn meal and corn-muffin mixes for the presence of a promoter commonly used in genetically modified foods, the cauliflower mosaic virus 35S…

Genetically Modified Crops and Nuisance: Exploring the Role of Precaution in Private Law

ERIC Educational Resources Information Center

Craik, Neil; Culver, Keith; Siebrasse, Norman

2007-01-01

This article critically considers calls for the precautionary principle to inform judicial decision making in a private law context in light of the Hoffman litigation, where it is alleged that the potential for genetic contamination from genetically modified (GM) crops causes an unreasonable interference with the rights of organic farmers to use…

Variables Affecting Secondary School Students' Willingness to Eat Genetically Modified Food Crops

ERIC Educational Resources Information Center

Maes, Jasmien; Bourgonjon, Jeroen; Gheysen, Godelieve; Valcke, Martin

2018-01-01

A large-scale cross-sectional study (N = 4002) was set up to determine Flemish secondary school students' willingness to eat genetically modified food (WTE) and to link students' WTE to previously identified key variables from research on the acceptance of genetic modification (GM). These variables include subjective and objective knowledge about…

Genetically modified yeast species, and fermentation processes using genetically modified yeast

DOEpatents

Rajgarhia, Vineet; Koivuranta, Kari; Penttila, Merja; Ilmen, Marja; Suominen, Pirkko; Aristidou, Aristos; Miller, Christopher Kenneth; Olson, Stacey; Ruohonen, Laura

2013-05-14

Yeast cells are transformed with an exogenous xylose isomerase gene. Additional genetic modifications enhance the ability of the transformed cells to ferment xylose to ethanol or other desired fermentation products. Those modifications include deletion of non-specific or specific aldose reductase gene(s), deletion of xylitol dehydrogenase gene(s) and/or overexpression of xylulokinase.

Genetically modified yeast species, and fermentation processes using genetically modified yeast

DOEpatents

Rajgarhia, Vineet; Koivuranta, Kari; Penttila, Merja; Ilmen, Marja; Suominen, Pirkko; Aristidou, Aristos; Miller, Christopher Kenneth; Olson, Stacey; Ruohonen, Laura

2017-09-12

Yeast cells are transformed with an exogenous xylose isomerase gene. Additional genetic modifications enhance the ability of the transformed cells to ferment xylose to ethanol or other desired fermentation products. Those modifications include deletion of non-specific or specific aldose reductase gene(s), deletion of xylitol dehydrogenase gene(s) and/or overexpression of xylulokinase.

Genetically modified yeast species and fermentation processes using genetically modified yeast

DOEpatents

Rajgarhia, Vineet [Kingsport, TN; Koivuranta, Kari [Helsinki, FI; Penttila, Merja [Helsinki, FI; Ilmen, Marja [Helsinki, FI; Suominen, Pirkko [Maple Grove, MN; Aristidou, Aristos [Maple Grove, MN; Miller, Christopher Kenneth [Cottage Grove, MN; Olson, Stacey [St. Bonifacius, MN; Ruohonen, Laura [Helsinki, FI

2011-05-17

Yeast cells are transformed with an exogenous xylose isomerase gene. Additional genetic modifications enhance the ability of the transformed cells to ferment xylose to ethanol or other desired fermentation products. Those modifications', include deletion of non-specific or specific aldose reductase gene(s), deletion of xylitol dehydrogenase gene(s) and/or overexpression of xylulokinase.

Genetically modified yeast species, and fermentation processes using genetically modified yeast

DOEpatents

Rajgarhia, Vineet; Koivuranta, Kari; Penttila, Merja; Ilmen, Marja; Suominen, Pirkko; Aristidou, Aristos; Miller, Christopher Kenneth; Olson, Stacey; Ruohonen, Laura

2016-08-09

Yeast cells are transformed with an exogenous xylose isomerase gene. Additional genetic modifications enhance the ability of the transformed cells to ferment xylose to ethanol or other desired fermentation products. Those modifications include deletion of non-specific or specific aldose reductase gene(s), deletion of xylitol dehydrogenase gene(s) and/or overexpression of xylulokinase.

Genetic Influence on the Expression of Hand Preferences in Chimpanzees (Pan Troglodytes): Evidence in Support of the Right-Shift Theory and Developmental Instability

PubMed Central

Hopkins, William D.; Dahl, Jeremy F.; Pilcher, Dawn

2007-01-01

Genetic mechanisms have been proposed to explain the pervasive representation of right-handedness in humans, whereas random, nongenetic factors have been posited to explain the lack of population-level right-handedness in nonhuman primates. We report evidence that hand preferences in chimpanzees are heritable, even among related individuals raised in different environments. Furthermore, we report that the degree of heritability is modified by factors associated with developmental instability, notably, offspring parity. The data are interpreted to reconcile both genetic models for handedness and hypotheses suggesting that developmental instability influences variation in handedness. PMID:11476096

Mixtures of genetically modified wheat lines outperform monocultures.

PubMed

Zeller, Simon L; Kalinina, Olena; Flynn, Dan F B; Schmid, Bernhard

2012-09-01

Biodiversity research shows that diverse plant communities are more stable and productive than monocultures. Similarly, populations in which genotypes with different pathogen resistance are mixed may have lower pathogen levels and thus higher productivity than genetically uniform populations. We used genetically modified (GM) wheat as a model system to test this prediction, because it allowed us to use genotypes that differed only in the trait pathogen resistance but were otherwise identical. We grew three such genotypes or lines in monocultures or two-line mixtures. Phenotypic measurements were taken at the level of individual plants and of entire plots (population level). We found that resistance to mildew increased with both GM richness (0, 1, or 2 Pm3 transgenes with different resistance specificities per plot) and GM concentration (0%, 50%, or 100% of all plants in a plot with a Pm3 transgene). Plots with two transgenes had 34.6% less mildew infection and as a consequence 7.3% higher seed yield than plots with one transgene. We conclude that combining genetic modification with mixed cropping techniques could be a promising approach to increase sustainability and productivity in agricultural systems, as the fitness cost of stacking transgenes within individuals may thus be avoided.

Regulated Apoptosis of Genetically-Modified Hematopoietic Stem and Progenitor Cells via an Inducible Caspase-9 Suicide Gene in Rhesus Macaques

PubMed Central

Barese, Cecilia N.; Felizardo, Tania C.; Sellers, Stephanie E.; Keyvanfar, Keyvan; Di Stasi, Antonio; Metzger, Mark E.; Krouse, Allen E.; Donahue, Robert E.; Spencer, David M.; Dunbar, Cynthia E.

2014-01-01

The high risk of insertional oncogenesis reported in clinical trials utilizing integrating retroviral vectors to genetically-modify hematopoietic stem and progenitor cells (HSPC) requires the development of safety strategies to minimize risks associated with novel cell and gene therapies. The ability to ablate genetically modified cells in vivo is desirable, should an abnormal clone emerge. Inclusion of “suicide genes” in vectors to facilitate targeted ablation of vector-containing abnormal clones in vivo is one potential safety approach. We tested whether the inclusion of the “inducible Caspase-9” (iCasp9) suicide gene in a gamma-retroviral vector facilitated efficient elimination of vector-containing HSPCs and their hematopoietic progeny in vivo long-term, in an autologous non-human primate transplantation model. Following stable engraftment of iCasp9 expressing hematopoietic cells in rhesus macaques, administration of AP1903, a chemical inducer of dimerization able to activate iCasp9, specifically eliminated vector-containing cells in all hematopoietic lineages long-term, suggesting activity at the HSPC level. Between 75–94% of vector-containing cells were eliminated by well-tolerated AP1903 dosing, but lack of complete ablation was linked to lower iCasp9 expression in residual cells. Further investigation of resistance mechanisms demonstrated upregulation of Bcl-2 in hematopoietic cell lines transduced with the vector and resistant to AP1903 ablation. These results demonstrate both the potential and the limitations of safety approaches utilizing iCasp9 to HSPC-targeted gene therapy settings, in a model with great relevance to clinical development. PMID:25330775

Genetic diversity and genetic structure of an endemic Mexican Dusky Rattlesnake (Crotalus triseriatus) in a highly modified agricultural landscape: implications for conservation.

PubMed

Sunny, Armando; Monroy-Vilchis, Octavio; Zarco-González, Martha M; Mendoza-Martínez, Germán David; Martínez-Gómez, Daniel

2015-12-01

It is necessary to determine genetic diversity of fragmented populations in highly modified landscapes to understand how populations respond to land-use change. This information will help guide future conservation and management strategies. We conducted a population genetic study on an endemic Mexican Dusky Rattlesnake (Crotalus triseriatus) in a highly modified landscape near the Toluca metropolitan area, in order to provide crucial information for the conservation of this species. There was medium levels of genetic diversity, with a few alleles and genotypes. We identified three genetically differentiated clusters, likely as a result of different habitat cover type. We also found evidence of an ancestral genetic bottleneck and medium values of effective population size. Inbreeding coefficients were low and there was a moderate gene flow. Our results can be used as a basis for future research and C. triseriatus conservation efforts, particularly considering that the Trans-Mexican Volcanic Belt is heavily impacted by destructive land-use practices.

The Evolution of Sex-Specific Dominance in Response to Sexually Antagonistic Selection.

PubMed

Spencer, Hamish G; Priest, Nicholas K

2016-05-01

Arguments about the evolutionary modification of genetic dominance have a long history in genetics, dating back more than 100 years. Mathematical investigations have shown that modifiers of the level of dominance at the locus of interest can spread at a reasonable rate only if heterozygotes at that locus are common. One hitherto neglected scenario is that of sexually antagonistic selection, which not only is ubiquitous in sexual species but also can generate stable high frequencies of heterozygotes that would appear to facilitate the spread of such modifiers. Here we present a mathematical model that shows that sexually specific dominance modification is a potential outcome of sexually antagonistic selection. Our model predicts that loci with higher levels of sexual conflict should exhibit greater differentiation between males and females in levels of dominance and that the strength of antagonistic selection experienced by one sex should be proportional to the level of dominance modification. We show that evidence from the literature is consistent with these predictions but suggest that empiricists should be alert to the possibility of there being numerous cases of sex-specific dominance. Further, in order to determine the significance of sexual conflict in the evolution of dominance, we need improved measures of sexual conflict and better characterization of loci that modify dominance of genes with sexually antagonistic fitness effects.

USEPA Resistance Management Research

EPA Science Inventory

A significant increase in genetically modified corn planting driven by biofuel demand is expected for future planted acreages approaching 80% of total corn plantings in 2009. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is...

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

Ruegg, Thomas Lawrence; Thelen, Michael P.

The present invention provides for a method of genetically modifying microorganisms to enhance resistance to ionic liquids, host cells genetically modified in accordance with the methods, and methods of using the host cells in a reaction comprising biomass that has been pretreated with ionic liquids.

Application of whole genome shotgun sequencing for detection and characterization of genetically modified organisms and derived products.

PubMed

Holst-Jensen, Arne; Spilsberg, Bjørn; Arulandhu, Alfred J; Kok, Esther; Shi, Jianxin; Zel, Jana

2016-07-01

The emergence of high-throughput, massive or next-generation sequencing technologies has created a completely new foundation for molecular analyses. Various selective enrichment processes are commonly applied to facilitate detection of predefined (known) targets. Such approaches, however, inevitably introduce a bias and are prone to miss unknown targets. Here we review the application of high-throughput sequencing technologies and the preparation of fit-for-purpose whole genome shotgun sequencing libraries for the detection and characterization of genetically modified and derived products. The potential impact of these new sequencing technologies for the characterization, breeding selection, risk assessment, and traceability of genetically modified organisms and genetically modified products is yet to be fully acknowledged. The published literature is reviewed, and the prospects for future developments and use of the new sequencing technologies for these purposes are discussed.

Development of a qualitative real-time PCR method to detect 19 targets for identification of genetically modified organisms.

PubMed

Peng, Cheng; Wang, Pengfei; Xu, Xiaoli; Wang, Xiaofu; Wei, Wei; Chen, Xiaoyun; Xu, Junfeng

2016-01-01

As the amount of commercially available genetically modified organisms (GMOs) grows recent years, the diversity of target sequences for molecular detection techniques are eagerly needed. Considered as the gold standard for GMO analysis, the real-time PCR technology was optimized to produce a high-throughput GMO screening method. With this method we can detect 19 transgenic targets. The specificity of the assays was demonstrated to be 100 % by the specific amplification of DNA derived from reference material from 20 genetically modified crops and 4 non modified crops. Furthermore, most assays showed a very sensitive detection, reaching the limit of ten copies. The 19 assays are the most frequently used genetic elements present in GM crops and theoretically enable the screening of the known GMO described in Chinese markets. Easy to use, fast and cost efficient, this method approach fits the purpose of GMO testing laboratories.

Between Development and Environment: Uncertainties of Agrofuels

ERIC Educational Resources Information Center

Leon Sicard, Tomas Enrique

2009-01-01

This article examines the dominant agricultural model in Colombia of which the emergence of biofuels is an inevitable and major consequence. Some uncertainties and complexities of the introduction of biofuels and the use of genetically modified crops are analyzed, including a general reflection on the possibilities of producing biofuels on the…

EVALUATING THE ROLE OF HABITAT QUALITY ON ESTABLISHMENT OF GM AGROSTIS STOLONIFERA PLANTS IN NON-AGRONOMIC SETTINGS

EPA Science Inventory

We compared soil chemistry and plant community data at non-agronomic mesic locations that either did or did not contain genetically modified (GM) Agrostis stolonifera. The best two-variable logistic regression model included soil Mn content and A. stolonifera cover and explained...

Glyphosate drift promotes changes in fitness and transgene flow in canola (Brassica napus) and hybrids

EPA Science Inventory

1. With the advent of transgenic crops, genetically modified, herbicide resistant B. napus has become a model system for examining the risks of escape of transgenes from cultivation and for evaluating potential ecological consequences of novel genes in wild species. 2. We exam...

MS-based analytical methodologies to characterize genetically modified crops.

PubMed

García-Cañas, Virginia; Simó, Carolina; León, Carlos; Ibáñez, Elena; Cifuentes, Alejandro

2011-01-01

The development of genetically modified crops has had a great impact on the agriculture and food industries. However, the development of any genetically modified organism (GMO) requires the application of analytical procedures to confirm the equivalence of the GMO compared to its isogenic non-transgenic counterpart. Moreover, the use of GMOs in foods and agriculture faces numerous criticisms from consumers and ecological organizations that have led some countries to regulate their production, growth, and commercialization. These regulations have brought about the need of new and more powerful analytical methods to face the complexity of this topic. In this regard, MS-based technologies are increasingly used for GMOs analysis to provide very useful information on GMO composition (e.g., metabolites, proteins). This review focuses on the MS-based analytical methodologies used to characterize genetically modified crops (also called transgenic crops). First, an overview on genetically modified crops development is provided, together with the main difficulties of their analysis. Next, the different MS-based analytical approaches applied to characterize GM crops are critically discussed, and include "-omics" approaches and target-based approaches. These methodologies allow the study of intended and unintended effects that result from the genetic transformation. This information is considered to be essential to corroborate (or not) the equivalence of the GM crop with its isogenic non-transgenic counterpart. Copyright © 2010 Wiley Periodicals, Inc.

Thorough Investigation of a Canine Autoinflammatory Disease (AID) Confirms One Main Risk Locus and Suggests a Modifier Locus for Amyloidosis

PubMed Central

Olsson, Mia; Tintle, Linda; Kierczak, Marcin; Perloski, Michele; Tonomura, Noriko; Lundquist, Andrew; Murén, Eva; Fels, Max; Tengvall, Katarina; Pielberg, Gerli; Dufaure de Citres, Caroline; Dorso, Laetitia; Abadie, Jérôme; Hanson, Jeanette; Thomas, Anne; Leegwater, Peter; Hedhammar, Åke; Lindblad-Toh, Kerstin; Meadows, Jennifer R. S.

2013-01-01

Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6×10−8) from each analysis showed that one haplotypic pair (H13-11) was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F ST) distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05) renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts. PMID:24130694

Advanced technologies for genetically manipulating the silkworm Bombyx mori, a model Lepidopteran insect

PubMed Central

Xu, Hanfu; O'Brochta, David A.

2015-01-01

Genetic technologies based on transposon-mediated transgenesis along with several recently developed genome-editing technologies have become the preferred methods of choice for genetically manipulating many organisms. The silkworm, Bombyx mori, is a Lepidopteran insect of great economic importance because of its use in silk production and because it is a valuable model insect that has greatly enhanced our understanding of the biology of insects, including many agricultural pests. In the past 10 years, great advances have been achieved in the development of genetic technologies in B. mori, including transposon-based technologies that rely on piggyBac-mediated transgenesis and genome-editing technologies that rely on protein- or RNA-guided modification of chromosomes. The successful development and application of these technologies has not only facilitated a better understanding of B. mori and its use as a silk production system, but also provided valuable experiences that have contributed to the development of similar technologies in non-model insects. This review summarizes the technologies currently available for use in B. mori, their application to the study of gene function and their use in genetically modifying B. mori for biotechnology applications. The challenges, solutions and future prospects associated with the development and application of genetic technologies in B. mori are also discussed. PMID:26108630

[Plant genetic engineering in Monsanto company: from the first laboratory experiments to worldwide practical use].

PubMed

Konov, A L; Velchev, M; Parcel, D

2005-01-01

The history of modern biotechnology of agricultural plants is briefly considered in the article. Methods of genetic transformation and regeneration of transgenic plants as well as the mechanisms of resistance of genetically modified plants to herbicides and pests are discussed. By the example of genetically modified varieties and hybrids there are shown the ways of solving the problem of weeds and pests. The questions of biosafety legislation in different countries are considered.

Bouc-Wen hysteresis model identification using Modified Firefly Algorithm

NASA Astrophysics Data System (ADS)

Zaman, Mohammad Asif; Sikder, Urmita

2015-12-01

The parameters of Bouc-Wen hysteresis model are identified using a Modified Firefly Algorithm. The proposed algorithm uses dynamic process control parameters to improve its performance. The algorithm is used to find the model parameter values that results in the least amount of error between a set of given data points and points obtained from the Bouc-Wen model. The performance of the algorithm is compared with the performance of conventional Firefly Algorithm, Genetic Algorithm and Differential Evolution algorithm in terms of convergence rate and accuracy. Compared to the other three optimization algorithms, the proposed algorithm is found to have good convergence rate with high degree of accuracy in identifying Bouc-Wen model parameters. Finally, the proposed method is used to find the Bouc-Wen model parameters from experimental data. The obtained model is found to be in good agreement with measured data.

Chemical characteristics and volatile profile of genetically modified peanut cultivars.

PubMed

Ng, Ee Chin; Dunford, Nurhan T; Chenault, Kelly

2008-10-01

Genetic engineering has been used to modify peanut cultivars for improving agronomic performance and pest resistance. Food products developed through genetic engineering have to be assessed for their safety before approval for human consumption. Preservation of desirable chemical, flavor and aroma attributes of the peanut cultivars during the genetic modifications is critical for acceptance of genetically modified peanuts (GMP) by the food industry. Hence, the main objective of this study is to examine chemical characteristics and volatile profile of GMP. The genetically modified peanut cultivars, 188, 540 and 654 were obtained from the USDA-ARS in Stillwater, Oklahoma. The peanut variety Okrun was examined as a control. The volatile analysis was performed using a gas chromatograph/mass spectrometer (GC/MS) equipped with an olfactory detector. The peanut samples were also analyzed for their moisture, ash, protein, sugar and oil compositions. Experimental results showed that the variations in nutritional composition of peanut lines examined in this study were within the values reported for existing cultivars. There were minor differences in volatile profile among the samples. The implication of this study is significant, since it shows that peanut cultivars with greater pest and fungal resistance were successfully developed without major changes in their chemical characteristics.

Wild worm embryogenesis harbors ubiquitous polygenic modifier variation.

PubMed

Paaby, Annalise B; White, Amelia G; Riccardi, David D; Gunsalus, Kristin C; Piano, Fabio; Rockman, Matthew V

2015-08-22

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture.

Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD).

PubMed

Lattante, Serena; Ciura, Sorana; Rouleau, Guy A; Kabashi, Edor

2015-05-01

Several genetic causes have been recently described for neurological diseases, increasing our knowledge of the common pathological mechanisms involved in these disorders. Mutation analysis has shown common causative factors for two major neurodegenerative disorders, ALS and FTD. Shared pathological and genetic markers as well as common neurological signs between these diseases have given rise to the notion of an ALS/FTD spectrum. This overlap among genetic factors causing ALS/FTD and the coincidence of mutated alleles (including causative, risk and modifier variants) have given rise to the notion of an oligogenic model of disease. In this review we summarize major advances in the elucidation of novel genetic factors in these diseases which have led to a better understanding of the common pathogenic factors leading to neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Open-Source Auto-Calibration Routine Supporting the Stormwater Management Model

NASA Astrophysics Data System (ADS)

Tiernan, E. D.; Hodges, B. R.

2017-12-01

The stormwater management model (SWMM) is a clustered model that relies on subcatchment-averaged parameter assignments to correctly capture catchment stormwater runoff behavior. Model calibration is considered a critical step for SWMM performance, an arduous task that most stormwater management designers undertake manually. This research presents an open-source, automated calibration routine that increases the efficiency and accuracy of the model calibration process. The routine makes use of a preliminary sensitivity analysis to reduce the dimensions of the parameter space, at which point a multi-objective function, genetic algorithm (modified Non-dominated Sorting Genetic Algorithm II) determines the Pareto front for the objective functions within the parameter space. The solutions on this Pareto front represent the optimized parameter value sets for the catchment behavior that could not have been reasonably obtained through manual calibration.

Autism spectrum disorder: neuropathology and animal models.

PubMed

Varghese, Merina; Keshav, Neha; Jacot-Descombes, Sarah; Warda, Tahia; Wicinski, Bridget; Dickstein, Dara L; Harony-Nicolas, Hala; De Rubeis, Silvia; Drapeau, Elodie; Buxbaum, Joseph D; Hof, Patrick R

2017-10-01

Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each. Postmortem examination of ASD brains has revealed global changes including disorganized gray and white matter, increased number of neurons, decreased volume of neuronal soma, and increased neuropil, the last reflecting changes in densities of dendritic spines, cerebral vasculature and glia. Both cortical and non-cortical areas show region-specific abnormalities in neuronal morphology and cytoarchitectural organization, with consistent findings reported from the prefrontal cortex, fusiform gyrus, frontoinsular cortex, cingulate cortex, hippocampus, amygdala, cerebellum and brainstem. The paucity of postmortem human studies linking neuropathology to the underlying etiology has been partly addressed using animal models to explore the impact of genetic and non-genetic factors clinically relevant for the ASD phenotype. Genetically modified models include those based on well-studied monogenic ASD genes (NLGN3, NLGN4, NRXN1, CNTNAP2, SHANK3, MECP2, FMR1, TSC1/2), emerging risk genes (CHD8, SCN2A, SYNGAP1, ARID1B, GRIN2B, DSCAM, TBR1), and copy number variants (15q11-q13 deletion, 15q13.3 microdeletion, 15q11-13 duplication, 16p11.2 deletion and duplication, 22q11.2 deletion). Models of idiopathic ASD include inbred rodent strains that mimic ASD behaviors as well as models developed by environmental interventions such as prenatal exposure to sodium valproate, maternal autoantibodies, and maternal immune activation. In addition to replicating some of the neuropathologic features seen in postmortem studies, a common finding in several animal models of ASD is altered density of dendritic spines, with the direction of the change depending on the specific genetic modification, age and brain region. Overall, postmortem neuropathologic studies with larger sample sizes representative of the various ASD risk genes and diverse clinical phenotypes are warranted to clarify putative etiopathogenic pathways further and to promote the emergence of clinically relevant diagnostic and therapeutic tools. In addition, as genetic alterations may render certain individuals more vulnerable to developing the pathological changes at the synapse underlying the behavioral manifestations of ASD, neuropathologic investigation using genetically modified animal models will help to improve our understanding of the disease mechanisms and enhance the development of targeted treatments.

Resistance Management Research for PIP Crops

EPA Science Inventory

A significant increase in genetically modified corn planting driven by biofuel demand is expected for future planted acreages approaching 80% of total corn plantings in 2009. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is...

Engineer Novel Anticancer Bioagents

DTIC Science & Technology

2010-10-01

selection (hence to create marker-free genetically modified organism – GMO as required by FDA regulations) have failed. The overall transformation...free genetically modified organism – GMO , as required by FDA regulations). Key Research Status 1. Reconstitution of a complete FK228 biosynthetic

Reparametrization-based estimation of genetic parameters in multi-trait animal model using Integrated Nested Laplace Approximation.

PubMed

Mathew, Boby; Holand, Anna Marie; Koistinen, Petri; Léon, Jens; Sillanpää, Mikko J

2016-02-01

A novel reparametrization-based INLA approach as a fast alternative to MCMC for the Bayesian estimation of genetic parameters in multivariate animal model is presented. Multi-trait genetic parameter estimation is a relevant topic in animal and plant breeding programs because multi-trait analysis can take into account the genetic correlation between different traits and that significantly improves the accuracy of the genetic parameter estimates. Generally, multi-trait analysis is computationally demanding and requires initial estimates of genetic and residual correlations among the traits, while those are difficult to obtain. In this study, we illustrate how to reparametrize covariance matrices of a multivariate animal model/animal models using modified Cholesky decompositions. This reparametrization-based approach is used in the Integrated Nested Laplace Approximation (INLA) methodology to estimate genetic parameters of multivariate animal model. Immediate benefits are: (1) to avoid difficulties of finding good starting values for analysis which can be a problem, for example in Restricted Maximum Likelihood (REML); (2) Bayesian estimation of (co)variance components using INLA is faster to execute than using Markov Chain Monte Carlo (MCMC) especially when realized relationship matrices are dense. The slight drawback is that priors for covariance matrices are assigned for elements of the Cholesky factor but not directly to the covariance matrix elements as in MCMC. Additionally, we illustrate the concordance of the INLA results with the traditional methods like MCMC and REML approaches. We also present results obtained from simulated data sets with replicates and field data in rice.

Genetic vulnerability to diabetes and obesity: does education offset the risk?

PubMed

Liu, S Y; Walter, S; Marden, J; Rehkopf, D H; Kubzansky, L D; Nguyen, T; Glymour, M M

2015-02-01

The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D. Copyright © 2014. Published by Elsevier Ltd.

Genetic engineering applied to agriculture has a long row to hoe.

PubMed

Miller, Henry I

2018-01-02

In spite of the lack of scientific justification for skepticism about crops modified with molecular techniques of genetic engineering, they have been the most scrutinized agricultural products in human history. The assumption that "genetically engineered" or "genetically modified" is a meaningful - and dangerous - classification has led to excessive and dilatory regulation. The modern molecular techniques are an extension, or refinement, of older, less precise, less predictable methods of genetic modification, but as long as today's activists and regulators remain convinced that so called "GMOs" represent a distinct and dangerous category of research and products, genetic engineering will fall short of its potential.

Genetically Modified Food: Knowledge and Attitude of Teachers and Students

NASA Astrophysics Data System (ADS)

Mohapatra, Animesh K.; Priyadarshini, Deepika; Biswas, Antara

2010-10-01

The concepts behind the technology of genetic modification of organisms and its applications are complex. A diverse range of opinions, public concern and considerable media interest accompanies the subject. This study explores the knowledge and attitudes of science teachers and senior secondary biology students about the application of a rapidly expanding technology, genetic engineering, to food production. The results indicated significant difference in understanding of concepts related with genetically engineered food stuffs between teachers and students. The most common ideas about genetically modified food were that cross bred plants and genetically modified plants are not same, GM organisms are produced by inserting a foreign gene into a plant or animal and are high yielding. More teachers thought that genetically engineered food stuffs were unsafe for the environment. Both teachers and students showed number of misconceptions, for example, the pesticidal proteins produced by GM organisms have indirect effects through bioaccumulation, induces production of allergic proteins, genetic engineering is production of new genes, GM plants are leaky sieves and that transgenes are more likely to introgress into wild species than mutated species. In general, more students saw benefits while teachers were cautious about the advantages of genetically engineered food stuffs.

Detection of Genetically Modified Maize in Processed Foods Sold Commercially in Iran by Qualitative PCR

PubMed Central

Rabiei, Maryam; Mehdizadeh, Mehrangiz; Rastegar, Hossein; Vahidi, Hossein; Alebouyeh, Mahmoud

2013-01-01

Detection of genetically modified organisms (GMOs) in food is an important issue for all the subjects involved in food control and customer’s right. Due to the increasing number of GMOs imported to Iran during the past few years, it has become necessary to screen the products in order to determine the identity of the consumed daily foodstuffs. In this study, following the extraction of genomic DNA from processed foods sold commercially in Iran, qualitative PCR was performed to detect genetically modified maize. The recombinant DNA target sequences were detected with primers highly specific for each investigated transgene such as CaMV35s gene, Bt-11, MON810 and Bt-176 separately. Based on the gel electrophoresis results, Bt- 11 and MON810 events were detected in some maize samples, while, in none of them Bt- 176 modified gene was detected. For the first time, the results demonstrate the presence of genetically modified maize in Iranian food products, reinforcing the need for the development of labeling system and valid quantitative methods in routine analyses. PMID:24250568

Detection of genetically modified maize in processed foods sold commercially in iran by qualitative PCR.

PubMed

Rabiei, Maryam; Mehdizadeh, Mehrangiz; Rastegar, Hossein; Vahidi, Hossein; Alebouyeh, Mahmoud

2013-01-01

Detection of genetically modified organisms (GMOs) in food is an important issue for all the subjects involved in food control and customer's right. Due to the increasing number of GMOs imported to Iran during the past few years, it has become necessary to screen the products in order to determine the identity of the consumed daily foodstuffs. In this study, following the extraction of genomic DNA from processed foods sold commercially in Iran, qualitative PCR was performed to detect genetically modified maize. The recombinant DNA target sequences were detected with primers highly specific for each investigated transgene such as CaMV35s gene, Bt-11, MON810 and Bt-176 separately. Based on the gel electrophoresis results, Bt- 11 and MON810 events were detected in some maize samples, while, in none of them Bt- 176 modified gene was detected. For the first time, the results demonstrate the presence of genetically modified maize in Iranian food products, reinforcing the need for the development of labeling system and valid quantitative methods in routine analyses.

Aquaculture: Incorporating risk assessment and risk management into public policies on genetically modified finfish and shellfish

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

Hallerman, E.M.; Kapuscinski, A.R.

Genetically modified finfish and shellfish pose economic benefits to aquaculture, but also pose ecological and genetic risks to ecosystems receiving such organisms. Realization of benefits with minimization of risks posed by a new technology can be addressed through the processes of risk assessment and risk management. Public policies adopted by individual countries will reflect differences in the outocme of risk assessment and risk management processes resulting from differences among the receiving ecosystems and sets of human values at issue. A number of countries and international institutions have begun development of policies for oversight of genetically modified aquatic organisms. In themore » United States, a working group commissioned by the U.S. Department of Agriculture incorporated risk assessment and risk management principles into draft performance standards for safely conducting research with genetically modified finfish and shellfish. The performance standards address research with a broad range of aquatic GMO`s and compliance is intended to be voluntary. In contrast, the Canadian policy mandates adherence to specified guidelines for experiments with transgenic aquatic organisms; establishment as national policy is expended soon.« less

'Inconstant males' and the maintenance of labile sex expression in subdioecious plants.

PubMed

Ehlers, Bodil K; Bataillon, Thomas

2007-01-01

* Here, we evaluate the role of pollen limitation and selfing in the maintenance of labile sex expression in subdioecious plant species. * We used a literature survey to explore which factors correlated with a significant occurrence of hermaphrodites in dioecious species. We developed models to explore the selective maintenance of labile sex expression. The models had similar ecological assumptions but differed in the genetic basis of sex lability. * We found that a significant frequency of hermaphrodites was associated with animal pollination, and that hermaphrodites were 'inconstant' males with perfect flowers, suggesting evolution through the gynodioecious pathway. Models showed that a modifier converting pure males into inconstant males could be maintained under a wide range of reduction in both male and female fitness. Pollen limitation and self-fertilization facilitated invasion of the modifier. Depending on the genetics of sex determination, we found pure dioecy, stable subdioecy (trioecy), and situations where inconstant males coexisted with either pure females or pure males. Under selfing and pollen limitation, certain conditions selected for inconstant males which will drive populations to extinction. * We discuss our results in relation to the evolution towards, and the breakdown of, dioecy, and the ecological and evolutionary implications of labile sex expression.

Resistance Management Monitoring For the US Corn Crop

EPA Science Inventory

Significant increases in genetically modified corn planting are expected for future planted acreages approaching 80% of total corn plantings anticipated by 2009. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is likely to in...

Implantation of Vascular Grafts Lined with Genetically Modified Endothelial Cells

NASA Astrophysics Data System (ADS)

Wilson, James M.; Birinyi, Louis K.; Salomon, Robert N.; Libby, Peter; Callow, Allan D.; Mulligan, Richard C.

1989-06-01

The possibility of using the vascular endothelial cell as a target for gene replacement therapy was explored. Recombinant retroviruses were used to transduce the lacZ gene into endothelial cells harvested from mongrel dogs. Prosthetic vascular grafts seeded with the genetically modified cells were implanted as carotid interposition grafts into the dogs from which the original cells were harvested. Analysis of the graft 5 weeks after implantation revealed genetically modified endothelial cells lining the luminal surface of the graft. This technology could be used in the treatment of atherosclerosis disease and the design of new drug delivery systems.

Application of a soft computing technique in predicting the percentage of shear force carried by walls in a rectangular channel with non-homogeneous roughness.

PubMed

Khozani, Zohreh Sheikh; Bonakdari, Hossein; Zaji, Amir Hossein

2016-01-01

Two new soft computing models, namely genetic programming (GP) and genetic artificial algorithm (GAA) neural network (a combination of modified genetic algorithm and artificial neural network methods) were developed in order to predict the percentage of shear force in a rectangular channel with non-homogeneous roughness. The ability of these methods to estimate the percentage of shear force was investigated. Moreover, the independent parameters' effectiveness in predicting the percentage of shear force was determined using sensitivity analysis. According to the results, the GP model demonstrated superior performance to the GAA model. A comparison was also made between the GP program determined as the best model and five equations obtained in prior research. The GP model with the lowest error values (root mean square error ((RMSE) of 0.0515) had the best function compared with the other equations presented for rough and smooth channels as well as smooth ducts. The equation proposed for rectangular channels with rough boundaries (RMSE of 0.0642) outperformed the prior equations for smooth boundaries.

Hdac6 Knock-Out Increases Tubulin Acetylation but Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease

PubMed Central

Bobrowska, Anna; Paganetti, Paolo; Matthias, Patrick; Bates, Gillian P.

2011-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC) inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6) in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF) from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD. PMID:21677773

Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models

PubMed Central

Hwang, In Young; Koh, Elvin; Wong, Adison; March, John C.; Bentley, William E.; Lee, Yung Seng; Chang, Matthew Wook

2017-01-01

Bacteria can be genetically engineered to kill specific pathogens or inhibit their virulence. We previously developed a synthetic genetic system that allows a laboratory strain of Escherichia coli to sense and kill Pseudomonas aeruginosa in vitro. Here, we generate a modified version of the system, including a gene encoding an anti-biofilm enzyme, and use the probiotic strain Escherichia coli Nissle 1917 as host. The engineered probiotic shows in vivo prophylactic and therapeutic activity against P. aeruginosa during gut infection in two animal models (Caenorhabditis elegans and mice). These findings support the further development of engineered microorganisms with potential prophylactic and therapeutic activities against gut infections. PMID:28398304

Wild worm embryogenesis harbors ubiquitous polygenic modifier variation

PubMed Central

Paaby, Annalise B; White, Amelia G; Riccardi, David D; Gunsalus, Kristin C; Piano, Fabio; Rockman, Matthew V

2015-01-01

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture. DOI: http://dx.doi.org/10.7554/eLife.09178.001 PMID:26297805

Differentiation of mixed biological traces in sexual assaults using DNA fragment analysis

PubMed Central

Apostolov, Аleksandar

2014-01-01

During the investigation of sexual abuse, it is not rare that mixed genetic material from two or more persons is detected. In such cases, successful profiling can be achieved using DNA fragment analysis, resulting in individual genetic profiles of offenders and their victims. This has led to an increase in the percentage of identified perpetrators of sexual offenses. The classic and modified genetic models used, allowed us to refine and implement appropriate extraction, polymerase chain reaction and electrophoretic procedures with individual assessment and approach to conducting research. Testing mixed biological traces using DNA fragment analysis appears to be the only opportunity for identifying perpetrators in gang rapes. PMID:26019514

Genetic polymorphisms in nitric oxide synthase genes modify the relationship between vegetable and fruit intake and risk of non-Hodgkin lymphoma

PubMed Central

Han, Xuesong; Zheng, Tongzhang; Lan, Qing; Zhang, Yaqun; Kilfoy, Briseis A.; Qin, Qin; Rothman, Nathaniel; Zahm, Shelia H.; Holford, Theodore R.; Leaderer, Brian; Zhang, Yawei

2010-01-01

Oxidative damage caused by reactive oxygen species (ROS) and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histological subtype in Connecticut women including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma (DLBCL) and Follicular lymphoma (FL). Two single nucleotide polymorphisms (SNPs) in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma (FL). When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruit were examined separately, strong interaction effects were narrowed to vegetable intake among DLBCL patients. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the nitric oxide synthase genes, modify the association between vegetable and fruit intake and risk of NHL. PMID:19423521

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

PubMed

Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

Use of murine models to detect the allergenicity of genetically modified Lactococcus lactis NZ9000/pNZPNK.

PubMed

Chiang, Shen-Shih; Liu, Chin-Feng; Ku, Ting-Wei; Mau, Jeng-Leun; Lin, Hsin-Tang; Pan, Tzu-Ming

2011-04-27

By introducing aprN into Lactococcus lactis NZ9000, the genetically modified L. lactis NZ9000/pNZPNK successfully expressed the nattokinase. The safety assessment of this novel strain was based on allergenicity of pepsin digestion stability and murine model serologic identity. Subjecting to the GM strain and host to pepsin digestion, the soluble fractions and cell debris were fast degraded completely. Feeding with ovalbumin resulted in significantly higher production of IgG1 and IgE as compared to that of L. lactis NZ9000/pNZPNK or L. lactis NZ9000. Further, the serum IgG2a level increased dose-dependently at week 2 and induced immune reaction toward Th1 pathway. Secretion of cytokines IL-4 and IL-10 fed with lactococci was significantly lower than that of the OVA group. L. lactis NZ9000/pNZPNK did not increase the proliferation of type 2 helper T cells in spleen or induce allergenicity in BALB/c mice. On the basis of the results, the new GM lactic acid bacterium is regarded as safe to use.

Relative Contribution of Genetic and Non-genetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

PubMed Central

Blackman, Scott M.; Deering-Brose, Rebecca; McWilliams, Rita; Naughton, Kathleen; Coleman, Barbara; Lai, Teresa; Algire, Marilyn; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Fallin, M. Daniele; West, Kristen; Arking, Dan E.; Chakravarti, Aravinda; Cutler, David J.; Cutting, Garry R

2006-01-01

Background & Aims Neonatal intestinal obstruction (meconium ileus or MI) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and non-genetic modifiers to the development of this major complication of CF. Methods Using clinical data and DNA collected by the CF Twin and Sibling Study, 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage. Results Specific mutations in CFTR, the gene responsible for CF, correlated with MI indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (p=1×10−5) demonstrating that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (DIOS; p=8×10−4). Unlike MI, concordance analysis indicated that the risk for development of DIOS in CF patients is primarily due to non-genetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene within the CFM1 region on chromosome 19 that had previously been linked to MI. Conclusions The CFTR gene along with two or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, while intestinal obstruction in older CF patients is primarily due to non-genetic factors. PMID:17030173

Adaptation of SUBSTOR for controlled-environment potato production with elevated carbon dioxide

NASA Technical Reports Server (NTRS)

Fleisher, D. H.; Cavazzoni, J.; Giacomelli, G. A.; Ting, K. C.; Janes, H. W. (Principal Investigator)

2003-01-01

The SUBSTOR crop growth model was adapted for controlled-environment hydroponic production of potato (Solanum tuberosum L. cv. Norland) under elevated atmospheric carbon dioxide concentration. Adaptations included adjustment of input files to account for cultural differences between the field and controlled environments, calibration of genetic coefficients, and adjustment of crop parameters including radiation use efficiency. Source code modifications were also performed to account for the absorption of light reflected from the surface below the crop canopy, an increased leaf senescence rate, a carbon (mass) balance to the model, and to modify the response of crop growth rate to elevated atmospheric carbon dioxide concentration. Adaptations were primarily based on growth and phenological data obtained from growth chamber experiments at Rutgers University (New Brunswick, N.J.) and from the modeling literature. Modified-SUBSTOR predictions were compared with data from Kennedy Space Center's Biomass Production Chamber for verification. Results show that, with further development, modified-SUBSTOR will be a useful tool for analysis and optimization of potato growth in controlled environments.

Landscape genetics as a tool for conservation planning: predicting the effects of landscape change on gene flow.

PubMed

van Strien, Maarten J; Keller, Daniela; Holderegger, Rolf; Ghazoul, Jaboury; Kienast, Felix; Bolliger, Janine

2014-03-01

For conservation managers, it is important to know whether landscape changes lead to increasing or decreasing gene flow. Although the discipline of landscape genetics assesses the influence of landscape elements on gene flow, no studies have yet used landscape-genetic models to predict gene flow resulting from landscape change. A species that has already been severely affected by landscape change is the large marsh grasshopper (Stethophyma grossum), which inhabits moist areas in fragmented agricultural landscapes in Switzerland. From transects drawn between all population pairs within maximum dispersal distance (< 3 km), we calculated several measures of landscape composition as well as some measures of habitat configuration. Additionally, a complete sampling of all populations in our study area allowed incorporating measures of population topology. These measures together with the landscape metrics formed the predictor variables in linear models with gene flow as response variable (F(ST) and mean pairwise assignment probability). With a modified leave-one-out cross-validation approach, we selected the model with the highest predictive accuracy. With this model, we predicted gene flow under several landscape-change scenarios, which simulated construction, rezoning or restoration projects, and the establishment of a new population. For some landscape-change scenarios, significant increase or decrease in gene flow was predicted, while for others little change was forecast. Furthermore, we found that the measures of population topology strongly increase model fit in landscape genetic analysis. This study demonstrates the use of predictive landscape-genetic models in conservation and landscape planning.

Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

PubMed

Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2015-02-01

The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of nonauthorized genetically modified organisms using differential quantitative polymerase chain reaction: application to 35S in maize.

PubMed

Cankar, Katarina; Chauvensy-Ancel, Valérie; Fortabat, Marie-Noelle; Gruden, Kristina; Kobilinsky, André; Zel, Jana; Bertheau, Yves

2008-05-15

Detection of nonauthorized genetically modified organisms (GMOs) has always presented an analytical challenge because the complete sequence data needed to detect them are generally unavailable although sequence similarity to known GMOs can be expected. A new approach, differential quantitative polymerase chain reaction (PCR), for detection of nonauthorized GMOs is presented here. This method is based on the presence of several common elements (e.g., promoter, genes of interest) in different GMOs. A statistical model was developed to study the difference between the number of molecules of such a common sequence and the number of molecules identifying the approved GMO (as determined by border-fragment-based PCR) and the donor organism of the common sequence. When this difference differs statistically from zero, the presence of a nonauthorized GMO can be inferred. The interest and scope of such an approach were tested on a case study of different proportions of genetically modified maize events, with the P35S promoter as the Cauliflower Mosaic Virus common sequence. The presence of a nonauthorized GMO was successfully detected in the mixtures analyzed and in the presence of (donor organism of P35S promoter). This method could be easily transposed to other common GMO sequences and other species and is applicable to other detection areas such as microbiology.

Finding the joker among the maize endogenous reference genes for genetically modified organism (GMO) detection.

PubMed

Paternò, Annalisa; Marchesi, Ugo; Gatto, Francesco; Verginelli, Daniela; Quarchioni, Cinzia; Fusco, Cristiana; Zepparoni, Alessia; Amaddeo, Demetrio; Ciabatti, Ilaria

2009-12-09

The comparison of five real-time polymerase chain reaction (PCR) methods targeted at maize ( Zea mays ) endogenous sequences is reported. PCR targets were the alcohol dehydrogenase (adh) gene for three methods and high-mobility group (hmg) gene for the other two. The five real-time PCR methods have been checked under repeatability conditions at several dilution levels on both pooled DNA template from several genetically modified (GM) maize certified reference materials (CRMs) and single CRM DNA extracts. Slopes and R(2) coefficients of all of the curves obtained from the adopted regression model were compared within the same method and among all of the five methods, and the limit of detection and limit of quantitation were analyzed for each PCR system. Furthermore, method equivalency was evaluated on the basis of the ability to estimate the target haploid genome copy number at each concentration level. Results indicated that, among the five methods tested, one of the hmg-targeted PCR systems can be considered equivalent to the others but shows the best regression parameters and a higher repeteability along the dilution range. Thereby, it is proposed as a valid module to be coupled to different event-specific real-time PCR for maize genetically modified organism (GMO) quantitation. The resulting practicability improvement on the analytical control of GMOs is discussed.

Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers.

PubMed

Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

2015-01-01

Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects.

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

Thein, S.L.; Weatherall, D.J.; Sampietro, M.

[open quotes]Heterocellular hereditary persistence of fetal hemoglobin[close quotes] (HPFH) is the term used to describe the genetically determined persistence of fetal hemoglobin (Hb F) production into adult life, in the absence of any related hematological disorder. Whereas some forms are caused by mutations in the [beta]-globin gene cluster on chromosome 11, others segregate independently. While the latter are of particular interest with respect to the regulation of globin gene switching, it has not been possible to determine their chromosomal location, mainly because their mode of inheritance is not clear, but also because several other factors are known to modify Hbmore » F production. The authors have examined a large Asian Indian pedigree which includes individuals with heterocellular HPFH associated with [beta]-thalassemia and/or [alpha]-thalassemia. Segregation analysis was conducted on the HPFH trait FC, defined to be the percentage of Hb F-containing cells (F-cells), using the class D regressive model. The results provide evidence for the presence of a major gene, dominant or codominant, which controls the FC values with residual familial correlations. The major gene was detected when the effects of genetic modifiers, notably [beta]-thalassemia and the XmnI-[sup G][gamma] polymorphism, are accounted for in this analysis. Linkage with the [beta]-globin gene cluster is excluded. The transmission of the FC values in this pedigree is informative enough to allow detection of linkage with an appropriate marker(s). The analytical approach outlined in this study, using simple regression to allow for genetic modifiers and thus allowing the mode of inheritance of a trait to be dissected out, may be useful as a model for segregation and linkage analyses of other complex phenotypes. 39 refs., 4 figs., 6 tabs.« less

The evolution of modern agriculture and its future with biotechnology.

PubMed

Harlander, Susan K

2002-06-01

Since the dawn of agriculture, humans have been manipulating crops to enhance their quality and yield. Via conventional breeding, seed producers have developed the modern corn hybrids and wheat commonly grown today. Newer techniques, such as radiation breeding, enhanced the seed producers' ability to develop new traits in crops. Then in the 1980's-1990's, scientists began applying genetic engineering techniques to improve crop quality and yield. In contrast to earlier breeding methods, these techniques raised questions about their safety to consumers and the environment. This paper provides an overview of the kinds of genetically modified crops developed and marketed to date and the value they provide farmers and consumers. The safety assessment process required for these crops is contrasted with the lack of a formal process required for traditionally bred crops. While European consumers have expressed concern about foods and animal feeds containing ingredients from genetically modified crops, Americans have largely been unconcerned or unaware of the presence of genetically modified foods on the market. This difference in attitude is reflected in Europe's decision to label foods containing genetically modified ingredients while no such labeling is required in the U.S. In the future, genetic modification will produce a variety of new products with enhanced nutritional or quality attributes.

Equality of Shapley value and fair proportion index in phylogenetic trees.

PubMed

Fuchs, Michael; Jin, Emma Yu

2015-11-01

The Shapley value and the fair proportion index of phylogenetic trees have been introduced recently for the purpose of making conservation decisions in genetics. Moreover, also very recently, Hartmann (J Math Biol 67:1163-1170, 2013) has presented data which shows that there is a strong correlation between a slightly modified version of the Shapley value (which we call the modified Shapley value) and the fair proportion index. He gave an explanation of this correlation by showing that the contribution of both indices to an edge of the tree becomes identical as the number of taxa tends to infinity. In this note, we show that the Shapley value and the fair proportion index are in fact the same. Moreover, we also consider the modified Shapley value and show that its covariance with the fair proportion index in random phylogenetic trees under the Yule-Harding model and uniform model is indeed close to one.

Generation of an immortalized mouse embryonic palatal mesenchyme cell line

PubMed Central

Soriano, Philippe

2017-01-01

Palatogenesis is a complex morphogenetic process, disruptions in which result in highly prevalent birth defects in humans. In recent decades, the use of model systems such as genetically-modified mice, mouse palatal organ cultures and primary mouse embryonic palatal mesenchyme (MEPM) cultures has provided significant insight into the molecular and cellular defects underlying cleft palate. However, drawbacks in each of these systems have prevented high-throughput, large-scale studies of palatogenesis in vitro. Here, we report the generation of an immortalized MEPM cell line that maintains the morphology, migration ability, transcript expression and responsiveness to exogenous growth factors of primary MEPM cells, with increased proliferative potential over primary cultures. The immortalization method described in this study will facilitate the generation of palatal mesenchyme cells with an unlimited capacity for expansion from a single genetically-modified mouse embryo and enable mechanistic studies of palatogenesis that have not been possible using primary culture. PMID:28582446

Detection of HbsAg and hATIII genetically modified goats (Caprahircus) by loop-mediated isothermal amplification.

PubMed

Tao, Chenyu; Zhang, Qingde; Zhai, Shanli; Liu, Bang

2013-11-01

In this study, sensitive and rapid detection systems were designed using a loop-mediated isothermal amplification (LAMP) method to detect the genetically modified goats. A set of 4 primers were designed for each exogenous nucleic acids HBsAg and hATIII. The DNA samples were first amplified with the outer and inner primers and released a single-stranded DNA,of which both ends were stem-loop structure. Then one inner primer hybridized with the loop, and initiated displacement synthesis in less than 1 h. The result could be visualized by both agarose gel electrophoresis and unaided eyes directly after adding SYBR GREEN 1. The detection limit of LAMP was ten copies of target molecules, indicating that LAMP was tenfold more sensitive than the classical PCR. Furthermore, all the samples of genetically modified goats were tested positively by LAMP, and the results demonstrated that the LAMP was a rapid and sensitive method for detecting the genetically modified organism.

Spatiotemporal patterns of non-genetically modified crops in the era of expansion of genetically modified food

PubMed Central

Sun, Jing; Wu, Wenbin; Tang, Huajun; Liu, Jianguo

2015-01-01

Despite heated debates over the safety of genetically modified (GM) food, GM crops have been expanding rapidly. Much research has focused on the expansion of GM crops. However, the spatiotemporal dynamics of non-genetically modified (non-GM) crops are not clear, although they may have significant environmental and agronomic impacts and important policy implications. To understand the dynamics of non-GM crops and to inform the debates among relevant stakeholders, we conducted spatiotemporal analyses of China’s major non-GM soybean production region, the Heilongjiang Province. Even though the total soybean planting area decreased from 2005 to 2010, surprisingly, there were hotspots of increase. The results also showed hotspots of loss as well as a large decline in the number and continuity of soybean plots. Since China is the largest non-GM soybean producer in the world, the decline of its major production region may signal the continual decline of global non-GM soybeans. PMID:26380899

Dual-reporter surrogate systems for efficient enrichment of genetically modified cells.

PubMed

Ren, Chonghua; Xu, Kun; Liu, Zhongtian; Shen, Juncen; Han, Furong; Chen, Zhilong; Zhang, Zhiying

2015-07-01

Isolation of genetically modified cells generated by designed nucleases are challenging, since they are often phenotypically indistinguishable from their parental cells. To efficiently enrich genetically modified cells, we developed two dual-reporter surrogate systems, namely NHEJ-RPG and SSA-RPG based on NHEJ and SSA repair mechanisms, respectively. Repair and enrichment efficiencies of these two systems were compared using different nucleases. In both CRISPR-Cas9- and ZFNs-induced DSB repair studies, we found that the efficiency and sensitivity of the SSA-RPG reporter with direct repeat length more than 200 bp were much higher than the NHEJ-RPG reporter. By utilizing the SSA-RPG reporter, we achieved the enrichment for indels in several endogenous loci with 6.3- to 34.8-fold of non-selected cells. Thus, the highly sensitive SSA-RPG reporter can be used for activity validation of designed nucleases and efficient enrichment of genetically modified cells. Besides, our systems offer alternative enrichment choices either by puromycin selection or FACS.

Spatiotemporal patterns of non-genetically modified crops in the era of expansion of genetically modified food.

PubMed

Sun, Jing; Wu, Wenbin; Tang, Huajun; Liu, Jianguo

2015-09-18

Despite heated debates over the safety of genetically modified (GM) food, GM crops have been expanding rapidly. Much research has focused on the expansion of GM crops. However, the spatiotemporal dynamics of non-genetically modified (non-GM) crops are not clear, although they may have significant environmental and agronomic impacts and important policy implications. To understand the dynamics of non-GM crops and to inform the debates among relevant stakeholders, we conducted spatiotemporal analyses of China's major non-GM soybean production region, the Heilongjiang Province. Even though the total soybean planting area decreased from 2005 to 2010, surprisingly, there were hotspots of increase. The results also showed hotspots of loss as well as a large decline in the number and continuity of soybean plots. Since China is the largest non-GM soybean producer in the world, the decline of its major production region may signal the continual decline of global non-GM soybeans.

Legal protection of public health through control over genetically modified food.

PubMed

Gutorova, Nataliya; Batyhina, Olena; Trotska, Maryna

2018-01-01

Introduction: Science is constantly being developed which leads to both positive and negative changes in public health and the environment. One of the results of scientific progress is introduction of food based on genetically modified organisms whose effects on human health, to date, remain scantily studied and are ambiguous. The aim: to determine how human health can be influenced by food production based on genetically modified organisms. Materials and methods: international acts, data of international organizations and conclusions of scientists have been examined and used in the study. The article also summarizes information from scientific journals and monographs from a medical and legal point of view with scientific methods. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. Conclusions: Genetically modified organisms are specific human-made organisms being a result of using modern biotechnology techniques. They have both positive and negative effects on human health and the environment. The main disadvantage is not sufficient study of them in various spheres of public life.

Of mice and men: molecular genetics of congenital heart disease.

PubMed

Andersen, Troels Askhøj; Troelsen, Karin de Linde Lind; Larsen, Lars Allan

2014-04-01

Congenital heart disease (CHD) affects nearly 1 % of the population. It is a complex disease, which may be caused by multiple genetic and environmental factors. Studies in human genetics have led to the identification of more than 50 human genes, involved in isolated CHD or genetic syndromes, where CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. The picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of cellular signaling components, from ligands and receptors, across down-stream effector molecules to transcription factors and co-factors, including chromatin modifiers.

Random regression models on Legendre polynomials to estimate genetic parameters for weights from birth to adult age in Canchim cattle.

PubMed

Baldi, F; Albuquerque, L G; Alencar, M M

2010-08-01

The objective of this work was to estimate covariance functions for direct and maternal genetic effects, animal and maternal permanent environmental effects, and subsequently, to derive relevant genetic parameters for growth traits in Canchim cattle. Data comprised 49,011 weight records on 2435 females from birth to adult age. The model of analysis included fixed effects of contemporary groups (year and month of birth and at weighing) and age of dam as quadratic covariable. Mean trends were taken into account by a cubic regression on orthogonal polynomials of animal age. Residual variances were allowed to vary and were modelled by a step function with 1, 4 or 11 classes based on animal's age. The model fitting four classes of residual variances was the best. A total of 12 random regression models from second to seventh order were used to model direct and maternal genetic effects, animal and maternal permanent environmental effects. The model with direct and maternal genetic effects, animal and maternal permanent environmental effects fitted by quadric, cubic, quintic and linear Legendre polynomials, respectively, was the most adequate to describe the covariance structure of the data. Estimates of direct and maternal heritability obtained by multi-trait (seven traits) and random regression models were very similar. Selection for higher weight at any age, especially after weaning, will produce an increase in mature cow weight. The possibility to modify the growth curve in Canchim cattle to obtain animals with rapid growth at early ages and moderate to low mature cow weight is limited.

The gravity of pollination: integrating at-site features into spatial analysis of contemporary pollen movement.

PubMed

DiLeo, Michelle F; Siu, Jenna C; Rhodes, Matthew K; López-Villalobos, Adriana; Redwine, Angela; Ksiazek, Kelly; Dyer, Rodney J

2014-08-01

Pollen-mediated gene flow is a major driver of spatial genetic structure in plant populations. Both individual plant characteristics and site-specific features of the landscape can modify the perceived attractiveness of plants to their pollinators and thus play an important role in shaping spatial genetic variation. Most studies of landscape-level genetic connectivity in plants have focused on the effects of interindividual distance using spatial and increasingly ecological separation, yet have not incorporated individual plant characteristics or other at-site ecological variables. Using spatially explicit simulations, we first tested the extent to which the inclusion of at-site variables influencing local pollination success improved the statistical characterization of genetic connectivity based upon examination of pollen pool genetic structure. The addition of at-site characteristics provided better models than those that only considered interindividual spatial distance (e.g. IBD). Models parameterized using conditional genetic covariance (e.g. population graphs) also outperformed those assuming panmixia. In a natural population of Cornus florida L. (Cornaceae), we showed that the addition of at-site characteristics (clumping of primary canopy opening above each maternal tree and maternal tree floral output) provided significantly better models describing gene flow than models including only between-site spatial (IBD) and ecological (isolation by resistance) variables. Overall, our results show that including interindividual and local ecological variation greatly aids in characterizing landscape-level measures of contemporary gene flow. © 2014 John Wiley & Sons Ltd.

Resistance Management Monitoring for the US Corn Crop to the Illinois Corn Growers Association

EPA Science Inventory

Significant increases in genetically modified corn planting are expected for future planted acreages approaching 80% of total corn plantings anticipated by 2009. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is likely to in...

TRACKING GENE FLOW FROM A GENETICALLY MODIFIED CREEPING BENTGRASS -- METHODS, MEASURES AND LESSONS LEARNED

EPA Science Inventory

Creeping bentgrass (CBG) expressing an engineered gene for resistance to glyphosate herbicide is one of the first genetically modified (GM) perennial crops to undergo regulatory review for commercial release by the US Department of Agriculture Animal Plant Health and Inspection S...

40 CFR 172.48 - Data requirements for a notification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS EXPERIMENTAL USE PERMITS Notification for Certain Genetically Modified Microbial Pesticides § 172... methods used to genetically modify the microbial pesticide. (h) The identity and location of the gene... organisms. (d) Information on survival and the ability of the microbial pesticide to increase in numbers...

Development of Cell Models as a Basis for Bioreactor Design for Genetically Modified Bacteria

DTIC Science & Technology

1986-10-30

of future behavior based on specifying the current state vector . Generally a total population greater than 10,000 is sufficient to allow treatment of...specifying the current state vector (essentially values for all variables in the model). Deterministic models become increasingly valid as the number of...host I A) and therein PARASItIS converts the host’s biomaterial or activities into its own + A and B are in physical contact. SYMBIOSIS (or perhaps Oi

The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

PubMed

Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

2007-01-01

The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

Electrotransformation and clonal isolation of Rickettsia species

PubMed Central

Riley, Sean P; Macaluso, Kevin R; Martinez, Juan J

2015-01-01

Genetic manipulation of obligate intracellular bacteria of the genus Rickettsia is currently undergoing a rapid period of change. The development of viable genetic tools, including replicative plasmids, transposons, homologous recombination, fluorescent protein-encoding genes, and antibiotic selectable markers has provided the impetus for future research development. This unit is designed to coalesce the basic methods pertaining to creation of genetically modified Rickettsia. The unit describes a series of methods, from inserting exogenous DNA into Rickettsia to the final isolation of genetically modified bacterial clones. Researchers working towards genetic manipulation of Rickettsia or similar obligate intracellular bacteria will find these protocols to be a valuable reference. PMID:26528784

Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-α-glucosidase

PubMed Central

Amalfitano, A.; McVie-Wylie, A. J.; Hu, H.; Dawson, T. L.; Raben, N.; Plotz, P.; Chen, Y. T.

1999-01-01

This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals. We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid α-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies. PMID:10430861

Gone with the Wind: Conceiving of Moral Responsibility in the Case of GMO Contamination.

PubMed

Robaey, Zoë

2016-06-01

Genetically modified organisms are a technology now used with increasing frequency in agriculture. Genetically modified seeds have the special characteristic of being living artefacts that can reproduce and spread; thus it is difficult to control where they end up. In addition, genetically modified seeds may also bring about uncertainties for environmental and human health. Where they will go and what effect they will have is therefore very hard to predict: this creates a puzzle for regulators. In this paper, I use the problem of contamination to complicate my ascription of forward-looking moral responsibility to owners of genetically modified organisms. Indeed, how can owners act responsibly if they cannot know that contamination has occurred? Also, because contamination creates new and unintended ownership, it challenges the ascription of forward-looking moral responsibility based on ownership. From a broader perspective, the question this paper aims to answer is as follows: how can we ascribe forward-looking moral responsibility when the effects of the technologies in question are difficult to know or unknown? To solve this problem, I look at the epistemic conditions for moral responsibility and connect them to the normative notion of the social experiment. Indeed, examining conditions for morally responsible experimentation helps to define a range of actions and to establish the related epistemic virtues that owners should develop in order to act responsibly where genetically modified organisms are concerned.

Environmental biosafety and transgenic potato in a centre of diversity for this crop.

PubMed

Celis, Carolina; Scurrah, Maria; Cowgill, Sue; Chumbiauca, Susana; Green, Jayne; Franco, Javier; Main, Gladys; Kiezebrink, Daan; Visser, Richard G F; Atkinson, Howard J

2004-11-11

The Nuffield Council on Bioethics suggests that introgression of genetic material into related species in centres of crop biodiversity is an insufficient justification to bar the use of genetically modified crops in the developing world. They consider that a precautionary approach to forgo the possible benefits invokes the fallacy of thinking that doing nothing is itself without risk to the poor. Here we report findings relevant to this and other aspects of environmental biosafety for genetically modified potato in its main centre of biodiversity, the central Andes. We studied genetically modified potato clones that provide resistance to nematodes, principal pests of Andean potato crops. We show that there is no harm to many non-target organisms, but gene flow occurs to wild relatives growing near potato crops. If stable introgression were to result, the fitness of these wild species could be altered. We therefore transformed the male sterile cultivar Revolucion to provide a genetically modified nematode-resistant potato to evaluate the benefits that this provides until the possibility of stable introgression to wild relatives is determined. Thus, scientific progress is possible without compromise to the precautionary principle.

Boosting for detection of gene-environment interactions.

PubMed

Pashova, H; LeBlanc, M; Kooperberg, C

2013-01-30

In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene-environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts with the genetic factors. In this paper, we develop a variant of L(2) boosting that is specifically designed to identify combinations of environmental variables that jointly modify the effect of a gene on a phenotype. Because the effect modifiers might have a small signal compared with the main effects, working in a space that is orthogonal to the main predictors allows us to focus on the interaction space. In a simulation study that investigates some plausible underlying model assumptions, our method outperforms the least absolute shrinkage and selection and Akaike Information Criterion and Bayesian Information Criterion model selection procedures as having the lowest test error. In an example for the Women's Health Initiative-Population Architecture using Genomics and Epidemiology study, the dedicated boosting method was able to pick out two single-nucleotide polymorphisms for which effect modification appears present. The performance was evaluated on an independent test set, and the results are promising. Copyright © 2012 John Wiley & Sons, Ltd.

Climate change and forest trees in the Pacific Northwest: guide to vulnerability assessment methodology

Treesearch

W. Devine; C. Aubry; J. Miller; K. Potter; A. Bower

2012-01-01

This guide provides a step-by-step description of the methodology used to apply the Forest Tree Genetic Risk Assessment System (ForGRAS; Potter and Crane 2010) to the tree species of the Pacific Northwest in a recent climate change vulnerability assessment (Devine et al. 2012). We describe our modified version of the ForGRAS model, and we review the model’s basic...

Creation of a Mouse with Stress-Induced Dystonia: Control of an ATPase Chaperone

DTIC Science & Technology

2013-04-01

was successful, and a mouse with the desired dystonic symptoms was obtained. It has two mutations , one a dominantly inherited gene with 100...the hallmark of dystonia. 15. SUBJECT TERMS Dystonia, genetically modified mice, stress, gene mutations , animal model of disease. 16...there are a variety of hypotheses that should be testable if there were a realistic animal model. Mice with mutations in genes known to cause dystonia

IL-9-Producing Mast Cell Precursors and Food Allergy

DTIC Science & Technology

2017-10-01

established genetically modified murine strains, a new reconstitution model of experimental food allergy, and the system to acquire duodenal biopsy...development in vivo using murine model of food allergy. Other Subtasks which are designed to study the molecular mechanisms underlying the FcεR signaling...for effective MMC9 expansion using FcεR deficient mice (Fig. 6). The cellular and molecular mechanisms underlining the FcεR signaling pathway will

ASSESSMENT OF ALLERGENIC POTENTIAL OF GENETICALLY MODIFIED FOODS: AN AGENDA FOR FUTURE RESEARCH

EPA Science Inventory

Abstract
Speakers and participants in the Workshop Assessment of the Allergenic Potential of Genetically Modified Foods met in breakout groups to discuss a number of issues including needs for future research. There was agreement that research should move forward quickly in t...

78 FR 25297 - Programmatic Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... environmental assessment (PEA) to evaluate the effects of the cultivation and use of genetically modified crops... genetically modified crops (GMCs) on our Refuge System lands. Our PEA will concentrate on the refuges in our... lands are those that have been evaluated and deregulated by the Animal and Plant Health Inspection...

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

EPA Science Inventory

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been ...

Evidence for the establishment and persistence of genetically modified canola populations in the U.S.

EPA Science Inventory

Background/Questions/Methods Concerns surrounding the commercial release of genetically modified crops include the risks of escape from cultivation, naturalization, and the transfer of beneficial traits to native and weedy species. Among the crops commonly grown in the U.S., a l...

Use of spectral imaging for insect resistance monitoring: EPA research on stewardship of Bt crops

EPA Science Inventory

A significant increase in genetically modified corn planting driven by biofuel demand is expected for future growing seasons. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is likely to increase. As part of the FIFRA regist...

Engineering species-like barriers to sexual reproduction.

PubMed

Maselko, Maciej; Heinsch, Stephen C; Chacón, Jeremy M; Harcombe, William R; Smanski, Michael J

2017-10-12

Controlling the exchange of genetic information between sexually reproducing populations has applications in agriculture, eradication of disease vectors, control of invasive species, and the safe study of emerging biotechnology applications. Here we introduce an approach to engineer a genetic barrier to sexual reproduction between otherwise compatible populations. Programmable transcription factors drive lethal gene expression in hybrid offspring following undesired mating events. As a proof of concept, we target the ACT1 promoter of the model organism Saccharomyces cerevisiae using a dCas9-based transcriptional activator. Lethal overexpression of actin results from mating this engineered strain with a strain containing the wild-type ACT1 promoter.Genetic isolation of a genetically modified organism represents a useful strategy for biocontainment. Here the authors use dCas9-VP64-driven gene expression to construct a 'species-like' barrier to reproduction between two otherwise compatible populations.

Chemical and Biological Tools for the Preparation of Modified Histone Proteins

PubMed Central

Howard, Cecil J.; Yu, Ruixuan R.; Gardner, Miranda L.; Shimko, John C.; Ottesen, Jennifer J.

2016-01-01

Eukaryotic chromatin is a complex and dynamic system in which the DNA double helix is organized and protected by interactions with histone proteins. This system is regulated through, a large network of dynamic post-translational modifications (PTMs) exists to ensure proper gene transcription, DNA repair, and other processes involving DNA. Homogenous protein samples with precisely characterized modification sites are necessary to better understand the functions of modified histone proteins. Here, we discuss sets of chemical and biological tools that have been developed for the preparation of modified histones, with a focus on the appropriate choice of tool for a given target. We start with genetic approaches for the creation of modified histones, including the incorporation of genetic mimics of histone modifications, chemical installation of modification analogs, and the use of the expanded genetic code to incorporate modified amino acids. Additionally, we will cover the chemical ligation techniques that have been invaluable in the generation of complex modified histones that are indistinguishable from the natural counterparts. Finally, we will end with a prospectus on future directions of synthetic chromatin in living systems. PMID:25863817

Evidence for Absolute Moral Opposition to Genetically Modified Food in the United States.

PubMed

Scott, Sydney E; Inbar, Yoel; Rozin, Paul

2016-05-01

Public opposition to genetic modification (GM) technology in the food domain is widespread (Frewer et al., 2013). In a survey of U.S. residents representative of the population on gender, age, and income, 64% opposed GM, and 71% of GM opponents (45% of the entire sample) were "absolutely" opposed-that is, they agreed that GM should be prohibited no matter the risks and benefits. "Absolutist" opponents were more disgust sensitive in general and more disgusted by the consumption of genetically modified food than were non-absolutist opponents or supporters. Furthermore, disgust predicted support for legal restrictions on genetically modified foods, even after controlling for explicit risk-benefit assessments. This research suggests that many opponents are evidence insensitive and will not be influenced by arguments about risks and benefits. © The Author(s) 2016.

Genetic modifiers of Velo- cardio- facial syndrome/DiGeorge syndrome

PubMed Central

Aggarwal, Vimla S.; Morrow, Bernice E.

2009-01-01

Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that Tbx1, a T- box containing transcription factor present on the deleted region, is likely responsible for the etiology of the syndrome. Furthermore, mutations in TBX1 have been found in rare non-deleted patients. Despite having the same sized deletion, most VCFS/DGS patients exhibit significant clinical variability. Stochastic, environmental and genetic factors likely modify the phenotype of patients with the disorder. Here, we review mouse genetics studies which may help identify genetic modifiers for VCFS/DGS. PMID:18636633

Review: Genetically modified plants for the promotion of human health.

PubMed

Yonekura-Sakakibara, Keiko; Saito, Kazuki

2006-12-01

Plants are attractive biological resources because of their ability to produce a huge variety of chemical compounds, and the familiarity of production in even the most rural settings. Genetic engineering gives plants additional characteristics and value for cultivation and post-harvest. Genetically modified (GM) plants of the "first generation" were conferred with traits beneficial to producers, whereas GM plants in subsequent "generations" are intended to provide beneficial traits for consumers. Golden Rice is a promising example of a GM plant in the second generation, and has overcome a number of obstacles for practical use. Furthermore, consumer-acceptable plants with health-promoting properties that are genetically modified using native genes are being developed. The emerging technology of metabolomics will also support the commercial realization of GM plants by providing comprehensive analyzes of plant biochemical components.

Comparison of tissue concentrations in male and female C57BL/6 mice

USDA-ARS?s Scientific Manuscript database

The tissue-specific response to dietary vitamin K (VK) manipulation has not been well studied in mice. This limits the use of genetically modified mouse models in VK studies. The objective of this study was to determine the sex-specific effects of dietary VK manipulation on serum, liver and extra-he...

Generation of germline ablated male pigs by CRISPR/Cas9 editing of the NANOS2 gene

USDA-ARS?s Scientific Manuscript database

Genome editing tools have revolutionized the generation of genetically modified animals including livestock. In particular, the domestic pig is a proven model of human physiology and an agriculturally important species. In this study, we utilized the CRISPR/Cas9 system to edit the NANOS2 gene in p...

A Murine Hypertrophic Cardiomyopathy Model: The DBA/2J Strain.

PubMed

Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Zhao, Fengbo; Gu, Qingqing; Williams, Robert W; Bhattacharya, Syamal K; Lu, Lu; Sun, Yao

2015-01-01

Familial hypertrophic cardiomyopathy (HCM) is attributed to mutations in genes that encode for the sarcomere proteins, especially Mybpc3 and Myh7. Genotype-phenotype correlation studies show significant variability in HCM phenotypes among affected individuals with identical causal mutations. Morphological changes and clinical expression of HCM are the result of interactions with modifier genes. With the exceptions of angiotensin converting enzyme, these modifiers have not been identified. Although mouse models have been used to investigate the genetics of many complex diseases, natural murine models for HCM are still lacking. In this study we show that the DBA/2J (D2) strain of mouse has sequence variants in Mybpc3 and Myh7, relative to widely used C57BL/6J (B6) reference strain and the key features of human HCM. Four-month-old of male D2 mice exhibit hallmarks of HCM including increased heart weight and cardiomyocyte size relative to B6 mice, as well as elevated markers for cardiac hypertrophy including β-myosin heavy chain (MHC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and skeletal muscle alpha actin (α1-actin). Furthermore, cardiac interstitial fibrosis, another feature of HCM, is also evident in the D2 strain, and is accompanied by up-regulation of type I collagen and α-smooth muscle actin (SMA)-markers of fibrosis. Of great interest, blood pressure and cardiac function are within the normal range in the D2 strain, demonstrating that cardiac hypertrophy and fibrosis are not secondary to hypertension, myocardial infarction, or heart failure. Because D2 and B6 strains have been used to generate a large family of recombinant inbred strains, the BXD cohort, the D2 model can be effectively exploited for in-depth genetic analysis of HCM susceptibility and modifier screens.

Ridge, Lasso and Bayesian additive-dominance genomic models.

PubMed

Azevedo, Camila Ferreira; de Resende, Marcos Deon Vilela; E Silva, Fabyano Fonseca; Viana, José Marcelo Soriano; Valente, Magno Sávio Ferreira; Resende, Márcio Fernando Ribeiro; Muñoz, Patricio

2015-08-25

A complete approach for genome-wide selection (GWS) involves reliable statistical genetics models and methods. Reports on this topic are common for additive genetic models but not for additive-dominance models. The objective of this paper was (i) to compare the performance of 10 additive-dominance predictive models (including current models and proposed modifications), fitted using Bayesian, Lasso and Ridge regression approaches; and (ii) to decompose genomic heritability and accuracy in terms of three quantitative genetic information sources, namely, linkage disequilibrium (LD), co-segregation (CS) and pedigree relationships or family structure (PR). The simulation study considered two broad sense heritability levels (0.30 and 0.50, associated with narrow sense heritabilities of 0.20 and 0.35, respectively) and two genetic architectures for traits (the first consisting of small gene effects and the second consisting of a mixed inheritance model with five major genes). G-REML/G-BLUP and a modified Bayesian/Lasso (called BayesA*B* or t-BLASSO) method performed best in the prediction of genomic breeding as well as the total genotypic values of individuals in all four scenarios (two heritabilities x two genetic architectures). The BayesA*B*-type method showed a better ability to recover the dominance variance/additive variance ratio. Decomposition of genomic heritability and accuracy revealed the following descending importance order of information: LD, CS and PR not captured by markers, the last two being very close. Amongst the 10 models/methods evaluated, the G-BLUP, BAYESA*B* (-2,8) and BAYESA*B* (4,6) methods presented the best results and were found to be adequate for accurately predicting genomic breeding and total genotypic values as well as for estimating additive and dominance in additive-dominance genomic models.

A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes

PubMed Central

Forget, Marie-Andrée; Tavera, René J.; Haymaker, Cara; Ramachandran, Renjith; Malu, Shuti; Zhang, Minying; Wardell, Seth; Fulbright, Orenthial J.; Toth, Chistopher Leroy; Gonzalez, Audrey M.; Thorsen, Shawne T.; Flores, Esteban; Wahl, Arely; Peng, Weiyi; Amaria, Rodabe N.; Hwu, Patrick; Bernatchez, Chantale

2017-01-01

Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center. PMID:28824634

The Spring of Systems Biology-Driven Breeding.

PubMed

Lavarenne, Jérémy; Guyomarc'h, Soazig; Sallaud, Christophe; Gantet, Pascal; Lucas, Mikaël

2018-05-12

Genetics and molecular biology have contributed to the development of rationalized plant breeding programs. Recent developments in both high-throughput experimental analyses of biological systems and in silico data processing offer the possibility to address the whole gene regulatory network (GRN) controlling a given trait. GRN models can be applied to identify topological features helping to shortlist potential candidate genes for breeding purposes. Time-series data sets can be used to support dynamic modelling of the network. This will enable a deeper comprehension of network behaviour and the identification of the few elements to be genetically rewired to push the system towards a modified phenotype of interest. This paves the way to design more efficient, systems biology-based breeding strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Compositions and methods for increased ethanol titer from biomass

DOEpatents

Jessen, Holly J.; Yi, Jian

2016-11-15

The present application discloses the identification of novel I. orientalis ADH1, ADHa, and ADHb genes, and the production and characterization of genetically modified yeast cells in which these genes were altered. Provided herein are isolated I. orientalis ADH1, ADHa, and ADHb polynucleotides and polypeptides, genetically modified yeast cells that overexpress I. orientalis ADH1 and/or contain deletions or disruptions of ADHa and/or ADHb, and methods of using culturing these modified cells to produce ethanol.

Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction.

PubMed

Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Bråthen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

2009-10-08

When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.

Horizontal gene transfer between bacteria.

PubMed

Heuer, Holger; Smalla, Kornelia

2007-01-01

Horizontal gene transfer (HGT) refers to the acquisition of foreign genes by organisms. The occurrence of HGT among bacteria in the environment is assumed to have implications in the risk assessment of genetically modified bacteria which are released into the environment. First, introduced genetic sequences from a genetically modified bacterium could be transferred to indigenous micro-organisms and alter their genome and subsequently their ecological niche. Second, the genetically modified bacterium released into the environment might capture mobile genetic elements (MGE) from indigenous micro-organisms which could extend its ecological potential. Thus, for a risk assessment it is important to understand the extent of HGT and genome plasticity of bacteria in the environment. This review summarizes the present state of knowledge on HGT between bacteria as a crucial mechanism contributing to bacterial adaptability and diversity. In view of the use of GM crops and microbes in agricultural settings, in this mini-review we focus particularly on the presence and role of MGE in soil and plant-associated bacteria and the factors affecting gene transfer.

Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction

PubMed Central

Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Bråthen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

2009-01-01

Background When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. Results We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). Conclusion We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs. PMID:19814792

Risk assessment model for development of advanced age-related macular degeneration.

PubMed

Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

2011-12-01

To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

CRISPR/Cas9 for Human Genome Engineering and Disease Research.

PubMed

Xiong, Xin; Chen, Meng; Lim, Wendell A; Zhao, Dehua; Qi, Lei S

2016-08-31

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, a versatile RNA-guided DNA targeting platform, has been revolutionizing our ability to modify, manipulate, and visualize the human genome, which greatly advances both biological research and therapeutics development. Here, we review the current development of CRISPR/Cas9 technologies for gene editing, transcription regulation, genome imaging, and epigenetic modification. We discuss the broad application of this system to the study of functional genomics, especially genome-wide genetic screening, and to therapeutics development, including establishing disease models, correcting defective genetic mutations, and treating diseases.

Gaps, inexperience, inconsistencies, and overlaps: crisis in the regulation of genetically modified plants and animals.

PubMed

Mandal, Gregory N

2004-04-01

The regulation of genetically modified products pursuant to statutes enacted decades prior to the advent of biotechnology has created a regulatory system that is passive rather than proactive about risks, has difficulty adapting to biotechnology advances, and is highly fractured and inefficient--transgenic plants and animals are governed by at least twelve different statutes and five different agencies or services. The deficiencies resulting from this piecemeal approach to regulation unnecessarily expose society and the environment to adverse risks of biotechnology and introduce numerous inefficiencies into the regulatory system. These risks and inefficiencies include gaps in regulation, duplicative and inconsistent regulation, unnecessary increases in the cost of and delay in the development and commercialization of new biotechnology products. These deficiencies also increase the risk of further unnecessary biotechnology scares, which may cause public overreaction against biotechnology products, preventing the maximization of social welfare. With science and society poised to soar from first-generation biotechnology (focused on crops modified for agricultural benefit), to next-generation developments (including transgenic fish, insects, and livestock, and pharmaceutical-producing and industrial compound-producing plants and animals), it is necessary to establish a comprehensive, efficient, and scientifically rigorous regulatory system. This Article details how to achieve such a result through fixing the deficiencies in, and risks created by, the current regulatory structure. Ignoring many details, the solutions can be summarized in two categories. First, statutory and regulatory gaps that are identified must be closed with new legislation and regulation. Second, regulation of genetically modified products must be shifted from a haphazard model based on statutes not intended to cover biotechnology to a system based upon agency expertise in handling particular types of risks.

DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

PubMed Central

Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

2016-01-01

Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

Synapse alterations in autism: Review of animal model findings.

PubMed

Zatkova, Martina; Bakos, Jan; Hodosy, Julius; Ostatnikova, Daniela

2016-06-01

Recent research has produced an explosion of experimental data on the complex neurobiological mechanisms of developmental disorders including autism. Animal models are one approach to studying the phenotypic features and molecular basis of autism. In this review, we describe progress in understanding synaptogenesis and alterations to this process with special emphasis on the cell adhesion molecules and scaffolding proteins implicated in autism. Genetic mouse model experiments are discussed in relation to alterations to selected synaptic proteins and consequent behavioral deficits measured in animal experiments. Pubmed databases were used to search for original and review articles on animal and human clinical studies on autism. The cell adhesion molecules, neurexin, neurolignin and the Shank family of proteins are important molecular targets associated with autism. The heterogeneity of the autism spectrum of disorders limits interpretation of information acquired from any single animal model or animal test. We showed synapse-specific/ model-specific defects associated with a given genotype in these models. Characterization of mouse models with genetic variations may help study the mechanisms of autism in humans. However, it will be necessary to apply new analytic paradigms in using genetically modified mice for understanding autism etiology in humans. Further studies are needed to create animal models with mutations that match the molecular and neural bases of autism.

Genetic consultation embedded in a gynecologic oncology clinic improves compliance with guideline-based care.

PubMed

Senter, Leigha; O'Malley, David M; Backes, Floor J; Copeland, Larry J; Fowler, Jeffery M; Salani, Ritu; Cohn, David E

2017-10-01

Analyze the impact of embedding genetic counseling services in gynecologic oncology on clinician referral and patient uptake of cancer genetics services. Data were reviewed for a total of 737 newly diagnosed epithelial ovarian cancer patients seen in gynecologic oncology at a large academic medical center including 401 from 11/2011-7/2014 (a time when cancer genetics services were provided as an off-site consultation). These data were compared to data from 8/2014-9/2016 (n=336), when the model changed to the genetics embedded model (GEM), incorporating a cancer genetic counselor on-site in the gynecologic oncology clinic. A statistically significant difference in proportion of patients referred pre- and post-GEM was observed (21% vs. 44%, p<0.0001). Pre-GEM, only 38% of referred patients were actually scheduled for genetics consultation and post-GEM 82% were scheduled (p<0.00001). The difference in the time from referral to scheduling in genetics was also statistically significant (3.92months pre-GEM vs. 0.79months post-GEM, p<0.00001) as was the time from referral to completion of genetics consultation (2.52months pre-GEM vs. 1.67months post-GEM, p<0.01). Twenty-five percent of patients referred post GEM were seen by the genetic counselor on the same day as the referral. Providing cancer genetics services on-site in gynecologic oncology and modifying the process by which patients are referred and scheduled significantly increases referral to cancer genetics and timely completion of genetics consultation, improving compliance with guideline-based care. Practice changes are critical given the impact of genetic test results on treatment and familial cancer risks. Copyright © 2017 Elsevier Inc. All rights reserved.

Integer programming model for optimizing bus timetable using genetic algorithm

NASA Astrophysics Data System (ADS)

Wihartiko, F. D.; Buono, A.; Silalahi, B. P.

2017-01-01

Bus timetable gave an information for passengers to ensure the availability of bus services. Timetable optimal condition happened when bus trips frequency could adapt and suit with passenger demand. In the peak time, the number of bus trips would be larger than the off-peak time. If the number of bus trips were more frequent than the optimal condition, it would make a high operating cost for bus operator. Conversely, if the number of trip was less than optimal condition, it would make a bad quality service for passengers. In this paper, the bus timetabling problem would be solved by integer programming model with modified genetic algorithm. Modification was placed in the chromosomes design, initial population recovery technique, chromosomes reconstruction and chromosomes extermination on specific generation. The result of this model gave the optimal solution with accuracy 99.1%.

DEVELOPMENT OF A MULTI-TIERED INSECT RESISTANCE MANAGEMENT PROGRAM FOR GENETICALLY MODIFIED CORN HYBRIDS EXPRESSING THE PLANT INCORPORATED PROTECTANT, BACILLUS THURINGIENSIS

EPA Science Inventory

A significant increase in genetically modified corn planting driven by biofuel demand is expected for the 2007 growing season with future planted acreages approaching 80% of total corn plantings anticipated by 2009. As demand increases, incidence of farmer non-compliance with ma...

L-malate production by metabolically engineered escherichia coli

DOEpatents

Zhang, Xueli; Wang, Xuan; Shanmugam, Keelnatham T.; Ingram, Lonnie O'Neal

2015-11-17

A process for the production of malic acid in commercially significant quantities from the carbon compounds by genetically modified bacterial strains (GMBS; also referred to as biocatalysts or genetically modified microorganisms) is disclosed. Microorganisms suitable for the production of malic acid can be cultured in one or two-step processes as disclosed herein.

Pulmonary arterial hypertension associated to systemic erythematous lupus: molecular characterization of 3 cases.

PubMed

Pousada, Guillermo; Lago-Docampo, Mauro; Baloira, Adolfo; Valverde, Diana

2018-03-08

Pulmonary arterial hypertension associated with systemic lupus erythematosus (PAH-SLE) is a rare disease with a low incidence rate. In this study, PAH related genes and genetic modifiers were characterised molecularly in patients with PAH-SLE. Three patients diagnosed with PAH-SLE and 100 control individuals were analysed after signing an informed consent. Two out of the three analysed patients with PAH-SLE were carriers of pathogenic mutations in the genes BMPR2 and ENG. After an in silico analysis, pathogenic mutations were searched for in control individuals and different databases, with negative results, and they were thus functionally analysed. The third patients only showed polymorphisms in the genes BMPR2, ACVRL1 and ENG. Several genetic variants and genetic modifiers were identified in the three analysed patients. These modifiers, along with the pathogenic mutations, could lead to a more severe clinical course in patients with PAH. We present, for the first time, patients with PAH-SLE carrying pathogenic mutations in the main genes related to PAH and alterations in the genetic modifiers. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Knowlege of, attitudes toward, and acceptance of genetically modified organisms among prospective teachers of biology, home economics, and grade school in Slovenia.

PubMed

Sorgo, Andrej; Ambrožič-Dolinšek, Jana

2010-05-01

The objective of this study was to investigate knowledge, opinions, and attitudes toward, as well as readiness to accept genetically modified organisms (GMOs) among prospective primary and secondary Slovene teachers. Our findings are that prospective teachers want to take an active role in rejecting or supporting individual GMOs and are aware of the importance of education about genetically modified organism (GMO) items and their potential significance for society. Through cluster analysis, we recognized four clusters of GMOs, separated by degree of genetically modified acceptability. GM plants and microorganisms which are recognized as useful are accepted. They are undecided about organisms used in research or medicine and reject organisms used for food consumption and for fun. There are only weak correlations between knowledge and attitudes and knowledge and acceptance of GMOs, and a strong correlation between attitudes and acceptance. The appropriate strategies and actions for improving university courses in biotechnology are discussed. Copyright © 2010 International Union of Biochemistry and Molecular Biology, Inc.

DNA degradation in genetically modified rice with Cry1Ab by food processing methods: implications for the quantification of genetically modified organisms.

PubMed

Xing, Fuguo; Zhang, Wei; Selvaraj, Jonathan Nimal; Liu, Yang

2015-05-01

Food processing methods contribute to DNA degradation, thereby affecting genetically modified organism detection and quantification. This study evaluated the effect of food processing methods on the relative transgenic content of genetically modified rice with Cry1Ab. In steamed rice and rice noodles, the levels of Cry1Ab were ⩾ 100% and <83%, respectively. Frying and baking in rice crackers contributed to a reduction in Pubi and Cry1Ab, while microwaving caused a decrease in Pubi and an increase in Cry1Ab. The processing methods of sweet rice wine had the most severe degradation effects on Pubi and Cry1Ab. In steamed rice and rice noodles, Cry1Ab was the most stable, followed by SPS and Pubi. However, in rice crackers and sweet rice wine, SPS was the most stable, followed by Cry1Ab and Pubi. Therefore, Cry1Ab is a better representative of transgenic components than is Pubi because the levels of Cry1Ab were less affected compared to Pubi. Copyright © 2014 Elsevier Ltd. All rights reserved.

A modified Wright-Fisher model that incorporates Ne: A variant of the standard model with increased biological realism and reduced computational complexity.

PubMed

Zhao, Lei; Gossmann, Toni I; Waxman, David

2016-03-21

The Wright-Fisher model is an important model in evolutionary biology and population genetics. It has been applied in numerous analyses of finite populations with discrete generations. It is recognised that real populations can behave, in some key aspects, as though their size that is not the census size, N, but rather a smaller size, namely the effective population size, Ne. However, in the Wright-Fisher model, there is no distinction between the effective and census population sizes. Equivalently, we can say that in this model, Ne coincides with N. The Wright-Fisher model therefore lacks an important aspect of biological realism. Here, we present a method that allows Ne to be directly incorporated into the Wright-Fisher model. The modified model involves matrices whose size is determined by Ne. Thus apart from increased biological realism, the modified model also has reduced computational complexity, particularly so when Ne⪡N. For complex problems, it may be hard or impossible to numerically analyse the most commonly-used approximation of the Wright-Fisher model that incorporates Ne, namely the diffusion approximation. An alternative approach is simulation. However, the simulations need to be sufficiently detailed that they yield an effective size that is different to the census size. Simulations may also be time consuming and have attendant statistical errors. The method presented in this work may then be the only alternative to simulations, when Ne differs from N. We illustrate the straightforward application of the method to some problems involving allele fixation and the determination of the equilibrium site frequency spectrum. We then apply the method to the problem of fixation when three alleles are segregating in a population. This latter problem is significantly more complex than a two allele problem and since the diffusion equation cannot be numerically solved, the only other way Ne can be incorporated into the analysis is by simulation. We have achieved good accuracy in all cases considered. In summary, the present work extends the realism and tractability of an important model of evolutionary biology and population genetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of enamel development using murine model systems: approaches and limitations

PubMed Central

Pugach, Megan K.; Gibson, Carolyn W.

2014-01-01

A primary goal of enamel research is to understand and potentially treat or prevent enamel defects related to amelogenesis imperfecta (AI). Rodents are ideal models to assist our understanding of how enamel is formed because they are easily genetically modified, and their continuously erupting incisors display all stages of enamel development and mineralization. While numerous methods have been developed to generate and analyze genetically modified rodent enamel, it is crucial to understand the limitations and challenges associated with these methods in order to draw appropriate conclusions that can be applied translationally, to AI patient care. We have highlighted methods involved in generating and analyzing rodent enamel and potential approaches to overcoming limitations of these methods: (1) generating transgenic, knockout, and knockin mouse models, and (2) analyzing rodent enamel mineral density and functional properties (structure and mechanics) of mature enamel. There is a need for a standardized workflow to analyze enamel phenotypes in rodent models so that investigators can compare data from different studies. These methods include analyses of gene and protein expression, developing enamel histology, enamel pigment, degree of mineralization, enamel structure, and mechanical properties. Standardization of these methods with regard to stage of enamel development and sample preparation is crucial, and ideally investigators can use correlative and complementary techniques with the understanding that developing mouse enamel is dynamic and complex. PMID:25278900

A genetic modifier suggests that endurance exercise exacerbates Huntington's disease

PubMed Central

Corrochano, Silvia; Blanco, Gonzalo; Williams, Debbie; Wettstein, Jessica; Simon, Michelle; Kumar, Saumya; Moir, Lee; Agnew, Thomas; Stewart, Michelle; Landman, Allison; Kotiadis, Vassilios N; Duchen, Michael R; Wackerhage, Henning; Rubinsztein, David C; Brown, Steve D M

2018-01-01

Abstract Polyglutamine expansions in the huntingtin gene cause Huntington’s disease (HD). Huntingtin is ubiquitously expressed, leading to pathological alterations also in peripheral organs. Variations in the length of the polyglutamine tract explain up to 70% of the age-at-onset variance, with the rest of the variance attributed to genetic and environmental modifiers. To identify novel disease modifiers, we performed an unbiased mutagenesis screen on an HD mouse model, identifying a mutation in the skeletal muscle voltage-gated sodium channel (Scn4a, termed ‘draggen’ mutation) as a novel disease enhancer. Double mutant mice (HD; Scn4aDgn/+) had decreased survival, weight loss and muscle atrophy. Expression patterns show that the main tissue affected is skeletal muscle. Intriguingly, muscles from HD; Scn4aDgn/+ mice showed adaptive changes similar to those found in endurance exercise, including AMPK activation, fibre type switching and upregulation of mitochondrial biogenesis. Therefore, we evaluated the effects of endurance training on HD mice. Crucially, this training regime also led to detrimental effects on HD mice. Overall, these results reveal a novel role for skeletal muscle in modulating systemic HD pathogenesis, suggesting that some forms of physical exercise could be deleterious in neurodegeneration. PMID:29509900

Mechanisms and Modifiers of Methylmercury-Induced Neurotoxicity

PubMed Central

Fretham, Stephanie JB; Caito, Samuel; Martinez-Finley, Ebany J; Aschner, Michael

2016-01-01

The neurotoxic consequences of methylmercury (MeHg) exposure have long been known, however a complete understanding of the mechanisms underlying this toxicity is elusive. Recent epidemiological and experimental studies have provided many mechanistic insights, particularly into the contribution of genetic and environmental factors that interact with MeHg to modify toxicity. This review will outline cellular processes directly and indirectly affected by MeHg, including oxidative stress, cellular signaling and gene expression, and discuss genetic, environmental and nutritional factors capable of modifying MeHg toxicity. PMID:27795823

Rapid construction of capsid-modified adenoviral vectors through bacteriophage lambda Red recombination.

PubMed

Campos, Samuel K; Barry, Michael A

2004-11-01

There are extensive efforts to develop cell-targeting adenoviral vectors for gene therapy wherein endogenous cell-binding ligands are ablated and exogenous ligands are introduced by genetic means. Although current approaches can genetically manipulate the capsid genes of adenoviral vectors, these approaches can be time-consuming and require multiple steps to produce a modified viral genome. We present here the use of the bacteriophage lambda Red recombination system as a valuable tool for the easy and rapid construction of capsid-modified adenoviral genomes.

Genetic Modification of Human Pancreatic Progenitor Cells Through Modified mRNA.

PubMed

Lu, Song; Chow, Christie C; Zhou, Junwei; Leung, Po Sing; Tsui, Stephen K; Lui, Kathy O

2016-01-01

In this chapter, we describe a highly efficient genetic modification strategy for human pancreatic progenitor cells using modified mRNA-encoding GFP and Neurogenin-3. The properties of modified mRNA offer an invaluable platform to drive protein expression, which has broad applicability in pathway regulation, directed differentiation, and lineage specification. This approach can also be used to regulate expression of other pivotal transcription factors during pancreas development and might have potential therapeutic values in regenerative medicine.

Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect.

PubMed

Wegmann, Udo; Carvalho, Ana Lucia; Stocks, Martin; Carding, Simon R

2017-05-23

The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the potential for the spread of transgenes in vivo in the mammalian gastrointestinal tract. We demonstrate the ability of GM-strains of Bacteroides to survive thymine starvation and overcome it through the exchange of genetic material. We also provide evidence for horizontal gene transfer in the mammalian gastrointestinal tract resulting in transgene-carrying wild type bacteria. These findings sound a strong note of caution on the employment of live genetically modified bacteria for the delivery of biologics.

[Genetically modified organisms in food--production, detection and risks].

PubMed

Zeljezić, Davor

2004-11-01

The first genetically modified plant (GMP) was a tobacco resistant to antibiotics in 1983. In 1996, the first genetically altered crop, a delayed-ripening tomato was commercially released. In the year 2003, the estimated global area of GM crops for was 67.7 million hectares. To produce such a plant a gene of interest has to be isolated from the donor. Together with a promoter, terminator sequence and marker gene it has to be introduced into the plant cell which is then stimulated to generate a whole GMP expressing new characteristics (herbicide/insect resistance, delayed ripening). The last few months have seen a strong public debate over genetically modified organisms which has raised scientific, economic, political, and ethical issues. Some questions concerning the safety of GMPs are still to be answered, and decisions about their future should be based on scientifically validated information.

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

PubMed Central

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A.; Schmidt, Marjanka K; van der Baan, Frederieke H.; Spurdle, Amanda B.; Walker, Logan C.; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B.; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E.; Blazer, Kathleen R.; Weitzel, Jeffrey N.; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E.; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A.M.; Meijers-Heijboer, Hanne E.J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P.G.; Hoogerbrugge, Nicoline; Ausems, Margreet G.E.M.; van Doorn, Helena C.; Collée, J. Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Szabo, Csilla I.; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E.; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L.; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan

2014-01-01

Background BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. PMID:25336561

A statistical assessment of differences and equivalences between genetically modified and reference plant varieties

PubMed Central

2011-01-01

Background Safety assessment of genetically modified organisms is currently often performed by comparative evaluation. However, natural variation of plant characteristics between commercial varieties is usually not considered explicitly in the statistical computations underlying the assessment. Results Statistical methods are described for the assessment of the difference between a genetically modified (GM) plant variety and a conventional non-GM counterpart, and for the assessment of the equivalence between the GM variety and a group of reference plant varieties which have a history of safe use. It is proposed to present the results of both difference and equivalence testing for all relevant plant characteristics simultaneously in one or a few graphs, as an aid for further interpretation in safety assessment. A procedure is suggested to derive equivalence limits from the observed results for the reference plant varieties using a specific implementation of the linear mixed model. Three different equivalence tests are defined to classify any result in one of four equivalence classes. The performance of the proposed methods is investigated by a simulation study, and the methods are illustrated on compositional data from a field study on maize grain. Conclusions A clear distinction of practical relevance is shown between difference and equivalence testing. The proposed tests are shown to have appropriate performance characteristics by simulation, and the proposed simultaneous graphical representation of results was found to be helpful for the interpretation of results from a practical field trial data set. PMID:21324199

WONOEP appraisal: new genetic approaches to study epilepsy

PubMed Central

Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

2014-01-01

Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non-coding RNAs involved in modifying gene expression following seizures. In addition, genetically-based bioluminescent reporters are providing new opportunities to assess neuronal activity and neurotransmitter levels both in vitro and in vivo in the context of epilepsy. Finally, genetically rederived neurons generated from patient iPS cells and genetically-modified zebrafish have become high-throughput means to investigate disease mechanisms and potential new therapies. Significance Genetics has considerably changed the field of epilepsy research and is paving the way for better diagnosis and therapies for patients with epilepsy. PMID:24965021

Development of a targeted transgenesis strategy in highly differentiated cells: a powerful tool for functional genomic analysis.

PubMed

Puttini, Stefania; Ouvrard-Pascaud, Antoine; Palais, Gael; Beggah, Ahmed T; Gascard, Philippe; Cohen-Tannoudji, Michel; Babinet, Charles; Blot-Chabaud, Marcel; Jaisser, Frederic

2005-03-16

Functional genomic analysis is a challenging step in the so-called post-genomic field. Identification of potential targets using large-scale gene expression analysis requires functional validation to identify those that are physiologically relevant. Genetically modified cell models are often used for this purpose allowing up- or down-expression of selected targets in a well-defined and if possible highly differentiated cell type. However, the generation of such models remains time-consuming and expensive. In order to alleviate this step, we developed a strategy aimed at the rapid and efficient generation of genetically modified cell lines with conditional, inducible expression of various target genes. Efficient knock-in of various constructs, called targeted transgenesis, in a locus selected for its permissibility to the tet inducible system, was obtained through the stimulation of site-specific homologous recombination by the meganuclease I-SceI. Our results demonstrate that targeted transgenesis in a reference inducible locus greatly facilitated the functional analysis of the selected recombinant cells. The efficient screening strategy we have designed makes possible automation of the transfection and selection steps. Furthermore, this strategy could be applied to a variety of highly differentiated cells.

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity

PubMed Central

Julik, Emily; Reyes-del Valle, Jorge

2017-01-01

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine. PMID:28934110

Intelligent Modeling Combining Adaptive Neuro Fuzzy Inference System and Genetic Algorithm for Optimizing Welding Process Parameters

NASA Astrophysics Data System (ADS)

Gowtham, K. N.; Vasudevan, M.; Maduraimuthu, V.; Jayakumar, T.

2011-04-01

Modified 9Cr-1Mo ferritic steel is used as a structural material for steam generator components of power plants. Generally, tungsten inert gas (TIG) welding is preferred for welding of these steels in which the depth of penetration achievable during autogenous welding is limited. Therefore, activated flux TIG (A-TIG) welding, a novel welding technique, has been developed in-house to increase the depth of penetration. In modified 9Cr-1Mo steel joints produced by the A-TIG welding process, weld bead width, depth of penetration, and heat-affected zone (HAZ) width play an important role in determining the mechanical properties as well as the performance of the weld joints during service. To obtain the desired weld bead geometry and HAZ width, it becomes important to set the welding process parameters. In this work, adaptative neuro fuzzy inference system is used to develop independent models correlating the welding process parameters like current, voltage, and torch speed with weld bead shape parameters like depth of penetration, bead width, and HAZ width. Then a genetic algorithm is employed to determine the optimum A-TIG welding process parameters to obtain the desired weld bead shape parameters and HAZ width.

Nature and nurture: environmental influences on a genetic rat model of depression.

PubMed

Mehta-Raghavan, N S; Wert, S L; Morley, C; Graf, E N; Redei, E E

2016-03-29

In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or 'nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, 'trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms.

Methods for genetic modification of megakaryocytes and platelets.

PubMed

Pendaries, Caroline; Watson, Stephen P; Spalton, Jennifer C

2007-09-01

During recent decades there have been major advances in the fields of thrombosis and haemostasis, in part through development of powerful molecular and genetic technologies. Nevertheless, genetic modification of megakaryocytes and generation of mutant platelets in vitro remains a highly specialized area of research. Developments are hampered by the low frequency of megakaryocytes and their progenitors, a poor efficiency of transfection and a lack of understanding with regard to the mechanism by which megakaryocytes release platelets. Current methods used in the generation of genetically modified megakaryocytes and platelets include mutant mouse models, cell line studies and use of viruses to transform primary megakaryocytes or haematopoietic precursor cells. This review summarizes the advantages, limitations and technical challenges of such methods, with a particular focus on recent successes and advances in this rapidly progressing field including the potential for use in gene therapy for treatment of patients with platelet disorders.

Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP).

PubMed

Mishra, Vikas; Karumuri, Bharat K; Gautier, Nicole M; Liu, Rui; Hutson, Timothy N; Vanhoof-Villalba, Stephanie L; Vlachos, Ioannis; Iasemidis, Leonidas; Glasscock, Edward

2017-06-01

People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings. The human epilepsy gene Kcna1 encodes voltage-gated Kv1.1 potassium channels that act to dampen neuronal excitability whereas Scn2a encodes voltage-gated Nav1.2 sodium channels important for action potential initiation and conduction. SUDEP-prone Kcna1-/- mice with partial genetic ablation of Nav1.2 channels (i.e. Scn2a+/-; Kcna1-/-) exhibited a two-fold increase in survival. Classical analysis of EEG and ECG recordings separately showed significantly decreased seizure durations in Scn2a+/-; Kcna1-/- mice compared with Kcna1-/- mice, without substantial modification of cardiac abnormalities. Novel analysis of the EEG and ECG together revealed a significant reduction in EEG-ECG association in Kcna1-/- mice compared with wild types, which was partially restored in Scn2a+/-; Kcna1-/- mice. The degree of EEG-ECG association was also proportional to the survival rate of mice across genotypes. These results show that Scn2a gene deletion acts as protective genetic modifier of SUDEP and suggest measures of brain-heart association as potential indices of SUDEP susceptibility. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Importance of Source: A Mixed Methods Analysis of Undergraduate Students' Attitudes toward Genetically Modified Food

ERIC Educational Resources Information Center

Ruth, Taylor K.; Rumble, Joy N.; Gay, Keegan D.; Rodriguez, Mary T.

2016-01-01

Even though science says genetically modified (GM) foods are safe, many consumers remain skeptical of the technology. Additionally, the scientific community has trouble communicating to the public, causing consumers to make uninformed decisions. The Millennial Generation will have more buying power than any other generation before them, and more…

METHODS FOR DETERMINING EXPOSURE TO AND POTENTIAL ECOLOGICAL EFFECTS OF GENE FLOW FROM GENETICALLY MODIFIED CROPS TO COMPATIBLE RELATIVES

EPA Science Inventory

SCIENCE QUESTIONS:

-Does gene flow occur from genetically modified (GM) crop plants to compatible plants?

-How can it be measured?

-Are there ecological consequences of GM crop gene flow to plant communities?



RESEARCH:

The objectives ...

Assessing Website Quality in Context: Retrieving Information about Genetically Modified Food on the Web

ERIC Educational Resources Information Center

McInerney, Claire R.; Bird, Nora J.

2005-01-01

Introduction: Knowing the credibility of information about genetically modified food on the Internet is critical to the everyday life information seeking of consumers as they form opinions about this nascent agricultural technology. The Website Quality Evaluation Tool (WQET) is a valuable instrument that can be used to determine the credibility of…

Geobacteraceae strains and methods

DOEpatents

Lovley, Derek R.; Nevin, Kelly P.; Yi, Hana

2015-07-07

Embodiments of the present invention provide a method of producing genetically modified strains of electricigenic microbes that are specifically adapted for the production of electrical current in microbial fuel cells, as well as strains produced by such methods and fuel cells using such strains. In preferred embodiments, the present invention provides genetically modified strains of Geobacter sulfurreducens and methods of using such strains.

News Media Use, Informed Issue Evaluation, and South Koreans' Support for Genetically Modified Foods

ERIC Educational Resources Information Center

Kim, Sei-Hill; Kim, Jeong-Nam; Choi, Doo-Hun; Jun, Sangil

2015-01-01

Analyzing survey data on the issue of genetically modified foods in South Korea, this study explores the role of news media in facilitating informed issue evaluation. Respondents who read a newspaper more often were more knowledgeable about the issue. Also, heavy newspaper readers were more able than light readers to hold "consistent"…

Opinion Building on a Socio-Scientific Issue: The Case of Genetically Modified Plants

ERIC Educational Resources Information Center

Ekborg, Margareta

2008-01-01

This paper presents results from a study with the following research questions: (a) are pupils' opinions on genetically modified organisms (GMOs) influenced by biology teaching; and (b) what is important for the opinion pupils hold and how does knowledge work together with other parameters such as values? 64 pupils in an upper secondary school…

Class Teacher Candidates' Opinions on Genetically Modified Organisms (GMO)

ERIC Educational Resources Information Center

Ural Keles, Pinar; Aydin, Suleyman

2017-01-01

This study was conducted to determine the Class teacher candidates' opinions on Genetically Modified Organisms. The study was carried out with 101 teacher candidates who were studying in the 3rd grade of Agri Ibrahim Çeçen University Classroom Teacher Department in 2016-2017 academic year. Of the students who participated in the survey, 56 were…

Learning to Argue as a Biotechnologist: Disprivileging Opposition to Genetically Modified Food

ERIC Educational Resources Information Center

Solli, Anne; Bach, Frank; Åkerman, Björn

2014-01-01

In the public discussion of genetically modified (GM) food the representations of science as a social good, conducted in the public interest to solve major problems are being subjected to intense scrutiny and questioning. Scientists working in these areas have been seen to struggle for the position of science in society. However few in situ…

Minimizing use of fish meal in sunshine bass diets using standard and new varieties of non-genetically modified soybeans

USDA-ARS?s Scientific Manuscript database

Improved plant ingredients are needed to support sustainable culture of carnivorous fish, such as hybrid striped bass (HSB). We are evaluating meals made from new strains of non-genetically-modified soybeans (non-GMO) with high protein and reduced anti-nutritional factors (ANFs) on HSB nutrient dige...

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. ...

[Genetically modified food--great unknown].

PubMed

Cichosz, G; Wiackowski, S K

2012-08-01

Genetically modified food (GMF) creates evident threat to consumers' health. In spite of assurances of biotechnologists, DNA of transgenic plants is instable, so, synthesis of foreign, allergenic proteins is possible. Due to high trypsin inhibitor content the GMF is digested much more slowly what, alike Bt toxin presence, increases probability of alimentary canal diseases. Next threats are bound to the presence of fitoestrogens and residues of Roundup pesticide, that can diminish reproductiveness; and even lead to cancerogenic transformation through disturbance of human hormonal metabolism. In spite of food producers and distributors assurances that food made of GMF raw materials is marked, de facto consumers have no choice. Moreover, along the food law products containing less than 0.9% of GMF protein are not included into genetically modified food.

Identification of prostate cancer modifier pathways using parental strain expression mapping

PubMed Central

Xu, Qing; Majumder, Pradip K.; Ross, Kenneth; Shim, Yeonju; Golub, Todd R.; Loda, Massimo; Sellers, William R.

2007-01-01

Inherited genetic risk factors play an important role in cancer. However, other than the Mendelian fashion cancer susceptibility genes found in familial cancer syndromes, little is known about risk modifiers that control individual susceptibility. Here we developed a strategy, parental strain expression mapping, that utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses to directly identify candidate germ-line modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and, specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with the findings in the murine models, in multiple human prostate expression data set, we found that enrichment of glycolysis pathways in normal tissues was associated with decreased rates of cancer recurrence after prostatectomy. Together, these data suggest that parental strain expression mapping can directly identify germ-line modifier pathways of relevance to human disease. PMID:17978178

Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

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

Li Huiwu; Health and Science Center, SIBS CAS and SSMU, 225 South Chongqing Road, Shanghai 200025; Dai Kerong

2007-05-18

In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a {beta}-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified bymore » BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals.« less

Automated DNA extraction from genetically modified maize using aminosilane-modified bacterial magnetic particles.

PubMed

Ota, Hiroyuki; Lim, Tae-Kyu; Tanaka, Tsuyoshi; Yoshino, Tomoko; Harada, Manabu; Matsunaga, Tadashi

2006-09-18

A novel, automated system, PNE-1080, equipped with eight automated pestle units and a spectrophotometer was developed for genomic DNA extraction from maize using aminosilane-modified bacterial magnetic particles (BMPs). The use of aminosilane-modified BMPs allowed highly accurate DNA recovery. The (A(260)-A(320)):(A(280)-A(320)) ratio of the extracted DNA was 1.9+/-0.1. The DNA quality was sufficiently pure for PCR analysis. The PNE-1080 offered rapid assay completion (30 min) with high accuracy. Furthermore, the results of real-time PCR confirmed that our proposed method permitted the accurate determination of genetically modified DNA composition and correlated well with results obtained by conventional cetyltrimethylammonium bromide (CTAB)-based methods.

Gene and environment interaction: is the differential susceptibility hypothesis relevant for obesity?

PubMed Central

Dalle Molle, Roberta; Fatemi, Hajar; Dagher, Alain; Levitan, Robert D.; Silveira, Patricia P.; Dubé, Laurette

2017-01-01

The differential susceptibility model states that a given genetic variant is associated with an increased risk of pathology in negative environments but greater than average resilience in enriched ones. While this theory was first implemented in psychiatric-genetic research, it may also help us to unravel the complex ways that genes and environments interact to influence feeding behavior and obesity. We reviewed evidence on gene vs. environment interactions that influence obesity development, aiming to support the applicability of the differential susceptibility model for this condition, and propose that various environmental “layers” relevant for human development should be considered when bearing the differential susceptibility model in mind. Mother-child relationship, socioeconomic status and individual's response are important modifiers of BMI and food intake when interacting with gene variants, “for better and for worse”. While only a few studies to date have investigated obesity outcomes using this approach, we propose that the differential susceptibility hypothesis is in fact highly applicable to the study of genetic and environmental influences on feeding behavior and obesity risk. PMID:28024828

CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients.

PubMed

Pelucchi, Sara; Mariani, Raffaella; Calza, Stefano; Fracanzani, Anna Ludovica; Modignani, Giulia Litta; Bertola, Francesca; Busti, Fabiana; Trombini, Paola; Fraquelli, Mirella; Forni, Gian Luca; Girelli, Domenico; Fargion, Silvia; Specchia, Claudia; Piperno, Alberto

2012-12-01

Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of the phenotype of hereditary hemochromatosis.

CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients

PubMed Central

Pelucchi, Sara; Mariani, Raffaella; Calza, Stefano; Fracanzani, Anna Ludovica; Modignani, Giulia Litta; Bertola, Francesca; Busti, Fabiana; Trombini, Paola; Fraquelli, Mirella; Forni, Gian Luca; Girelli, Domenico; Fargion, Silvia; Specchia, Claudia; Piperno, Alberto

2012-01-01

Background Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. Design and Methods: In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. Results We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. Conclusions While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of the phenotype of hereditary hemochromatosis. PMID:22773607

[Detection of genetically modified soy (Roundup-Ready) in processed food products].

PubMed

Hagen, M; Beneke, B

2000-01-01

In this study, the application of a qualitative and a quantitative method of analysis to detect genetically modified RR-Soy (Roundup-Ready Soy) in processed foods is described. A total of 179 various products containing soy such as baby food and diet products, soy drinks and desserts, tofu and tofu products, soy based meat substitutes, soy protein, breads, flour, granules, cereals, noodles, soy bean sprouts, fats and oils as well as condiments were investigated following the pattern of the section 35 LMBG-method L 23.01.22-1. The DNA was extracted from the samples and analysed using a soybean specific lectin gene PCR as well as a PCR, specific for the genetic modification. Additional, by means of PCR in combination with fluorescence-detection (TaqMan 5'-Nuclease Assay), suspicious samples were subjected to a real-time quantification of the percentage of genetically modified RR-Soy. The methods of analysis proved to be extremely sensitive and specific in regard to the food groups checked. The fats and oils, as well as the condiments were the exceptions in which amplifiable soy DNA could not be detected. The genetic modification of RR-Soy was detected in 34 samples. Eight of these samples contained more than 1% of RR-Soy. It is necessary to determine the percentage of transgenic soy in order to assess whether genetically modified ingredients were deliberately added, or whether they were caused by technically unavoidable contamination (for example during transportation and processing).

Unified framework to evaluate panmixia and migration direction among multiple sampling locations.

PubMed

Beerli, Peter; Palczewski, Michal

2010-05-01

For many biological investigations, groups of individuals are genetically sampled from several geographic locations. These sampling locations often do not reflect the genetic population structure. We describe a framework using marginal likelihoods to compare and order structured population models, such as testing whether the sampling locations belong to the same randomly mating population or comparing unidirectional and multidirectional gene flow models. In the context of inferences employing Markov chain Monte Carlo methods, the accuracy of the marginal likelihoods depends heavily on the approximation method used to calculate the marginal likelihood. Two methods, modified thermodynamic integration and a stabilized harmonic mean estimator, are compared. With finite Markov chain Monte Carlo run lengths, the harmonic mean estimator may not be consistent. Thermodynamic integration, in contrast, delivers considerably better estimates of the marginal likelihood. The choice of prior distributions does not influence the order and choice of the better models when the marginal likelihood is estimated using thermodynamic integration, whereas with the harmonic mean estimator the influence of the prior is pronounced and the order of the models changes. The approximation of marginal likelihood using thermodynamic integration in MIGRATE allows the evaluation of complex population genetic models, not only of whether sampling locations belong to a single panmictic population, but also of competing complex structured population models.

Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research.

PubMed

Siciliano, Giulia; Alano, Pietro

2015-01-01

The unicellular protozoan parasites of the genus Plasmodium impose on human health worldwide the enormous burden of malaria. The possibility to genetically modify several species of malaria parasites represented a major advance in the possibility to elucidate their biology and is now turning laboratory lines of transgenic Plasmodium into precious weapons to fight malaria. Amongst the various genetically modified plasmodia, transgenic parasite lines expressing bioluminescent reporters have been essential to unveil mechanisms of parasite gene expression and to develop in vivo imaging approaches in mouse malaria models. Mainly the human malaria parasite Plasmodium falciparum and the rodent parasite P. berghei have been engineered to express bioluminescent reporters in almost all the developmental stages of the parasite along its complex life cycle between the insect and the vertebrate hosts. Plasmodium lines expressing conventional and improved luciferase reporters are now gaining a central role to develop cell based assays in the much needed search of new antimalarial drugs and to open innovative approaches for both fundamental and applied research in malaria.

Branch-pipe-routing approach for ships using improved genetic algorithm

NASA Astrophysics Data System (ADS)

Sui, Haiteng; Niu, Wentie

2016-09-01

Branch-pipe routing plays fundamental and critical roles in ship-pipe design. The branch-pipe-routing problem is a complex combinatorial optimization problem and is thus difficult to solve when depending only on human experts. A modified genetic-algorithm-based approach is proposed in this paper to solve this problem. The simplified layout space is first divided into threedimensional (3D) grids to build its mathematical model. Branch pipes in layout space are regarded as a combination of several two-point pipes, and the pipe route between two connection points is generated using an improved maze algorithm. The coding of branch pipes is then defined, and the genetic operators are devised, especially the complete crossover strategy that greatly accelerates the convergence speed. Finally, simulation tests demonstrate the performance of proposed method.

A minimally sufficient model for rib proximal-distal patterning based on genetic analysis and agent-based simulations

PubMed Central

Mah, In Kyoung

2017-01-01

For decades, the mechanism of skeletal patterning along a proximal-distal axis has been an area of intense inquiry. Here, we examine the development of the ribs, simple structures that in most terrestrial vertebrates consist of two skeletal elements—a proximal bone and a distal cartilage portion. While the ribs have been shown to arise from the somites, little is known about how the two segments are specified. During our examination of genetically modified mice, we discovered a series of progressively worsening phenotypes that could not be easily explained. Here, we combine genetic analysis of rib development with agent-based simulations to conclude that proximal-distal patterning and outgrowth could occur based on simple rules. In our model, specification occurs during somite stages due to varying Hedgehog protein levels, while later expansion refines the pattern. This framework is broadly applicable for understanding the mechanisms of skeletal patterning along a proximal-distal axis. PMID:29068314

Brain-derived neurotrophic factor as a model system for examining gene by environment interactions across development.

PubMed

Casey, B J; Glatt, C E; Tottenham, N; Soliman, F; Bath, K; Amso, D; Altemus, M; Pattwell, S; Jones, R; Levita, L; McEwen, B; Magariños, A M; Gunnar, M; Thomas, K M; Mezey, J; Clark, A G; Hempstead, B L; Lee, F S

2009-11-24

There has been a dramatic rise in gene x environment studies of human behavior over the past decade that have moved the field beyond simple nature versus nurture debates. These studies offer promise in accounting for more variability in behavioral and biological phenotypes than studies that focus on genetic or experiential factors alone. They also provide clues into mechanisms of modifying genetic risk or resilience in neurodevelopmental disorders. Yet, it is rare that these studies consider how these interactions change over the course of development. In this paper, we describe research that focuses on the impact of a polymorphism in a brain-derived neurotrophic factor (BDNF) gene, known to be involved in learning and development. Specifically we present findings that assess the effects of genotypic and environmental loadings on neuroanatomic and behavioral phenotypes across development. The findings illustrate the use of a genetic mouse model that mimics the human polymorphism, to constrain the interpretation of gene-environment interactions across development in humans.

Identification of five novel modifier loci of ApcMin harbored in the BXH14 recombinant inbred strain

PubMed Central

Siracusa, Linda D.

2012-01-01

Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc Min mouse model carries a point mutation in the Apc gene and develops polyps along the intestinal tract. Inbred strain background influences polyp phenotypes in Apc Min mice. Several Modifier of Min (Mom) loci that alter tumor phenotypes associated with the Apc Min mutation have been identified to date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females with C57BL/6J (B6) Apc Min males and quantitating tumor phenotypes in backcross progeny. We found that the BXH14 RI strain harbors five modifier loci that decrease polyp multiplicity. Furthermore, we show that resistance is determined by varying combinations of these modifier loci. Gene interaction network analysis shows that there are multiple networks with proven gene–gene interactions, which contain genes from all five modifier loci. We discuss the implications of this result for studies that define susceptibility loci, namely that multiple networks may be acting concurrently to alter tumor phenotypes. Thus, the significance of this work resides not only with the modifier loci we identified but also with the combinations of loci needed to get maximal protection against polyposis and the impact of this finding on human disease studies. Abbreviations:APCadenomatous polyposis coliGWASgenome-wide association studiesQTLquantitative trait lociSNPsingle-nucleotide polymorphism. PMID:22637734

Genetically engineered mouse models and human osteosarcoma

PubMed Central

2012-01-01

Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics. PMID:23036272

Gene knockdown by morpholino-modified oligonucleotides in the zebrafish (Danio rerio) model: applications for developmental toxicology.

PubMed

Timme-Laragy, Alicia R; Karchner, Sibel I; Hahn, Mark E

2012-01-01

The zebrafish (Danio rerio) has long been used as a model for developmental biology, making it an excellent model to use also in developmental toxicology. The many advantages of zebrafish include their small size, prolific spawning, rapid development, and transparent embryos. They can be easily manipulated genetically through the use of transgenic technology and gene knockdown via morpholino-modified antisense oligonucleotides (MOs). Knocking down specific genes to assess their role in the response to toxicant exposure provides a way to further our knowledge of how developmental toxicants work on a molecular and mechanistic level while establishing a relationship between these molecular events and morphological, behavioral, and/or physiological effects (i.e., phenotypic anchoring). In this chapter, we address important considerations for using MOs to study developmental toxicology in zebrafish embryos and provide a protocol for their use.

Gene knockdown by morpholino-modified oligonucleotides in the zebrafish model: applications for developmental toxicology

PubMed Central

Timme-Laragy, Alicia R.; Karchner, Sibel I.; Hahn, Mark E.

2014-01-01

Summary The zebrafish (Danio rerio) has long been used as a model for developmental biology, making it an excellent model to use also in developmental toxicology. The many advantages of zebrafish include their small size, prolific spawning, rapid development, and transparent embryos. They can be easily manipulated genetically through the use of transgenic technology and gene knock-down via morpholino-modified antisense oligonucleotides (MOs). Knocking down specific genes to assess their role in the response to toxicant exposure provides a way to further our knowledge of how developmental toxicants work on a molecular and mechanistic level, while establishing a relationship between these molecular events and morphological, behavioral, and/or physiological effects (i.e. phenotypic anchoring). In this chapter we address important considerations for using MOs to study developmental toxicology in zebrafish embryos and provide a protocol for their use. PMID:22669659

Evidence for transgenerational metabolic programming in Drosophila

PubMed Central

Buescher, Jessica L.; Musselman, Laura P.; Wilson, Christina A.; Lang, Tieming; Keleher, Madeline; Baranski, Thomas J.; Duncan, Jennifer G.

2013-01-01

SUMMARY Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie) feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon. PMID:23649823

Decade Review (1999-2009): Artificial Intelligence Techniques in Student Modeling

NASA Astrophysics Data System (ADS)

Drigas, Athanasios S.; Argyri, Katerina; Vrettaros, John

Artificial Intelligence applications in educational field are getting more and more popular during the last decade (1999-2009) and that is why much relevant research has been conducted. In this paper, we present the most interesting attempts to apply artificial intelligence methods such as fuzzy logic, neural networks, genetic programming and hybrid approaches such as neuro - fuzzy systems and genetic programming neural networks (GPNN) in student modeling. This latest research trend is a part of every Intelligent Tutoring System and aims at generating and updating a student model in order to modify learning content to fit individual needs or to provide reliable assessment and feedback to student's answers. In this paper, we make a brief presentation of methods used to point out their qualities and then we attempt a navigation to the most representative studies sought in the decade of our interest after classifying them according to the principal aim they attempted to serve.

Transgenic and gene knockout mice in gastric cancer research

PubMed Central

Jiang, Yannan; Yu, Yingyan

2017-01-01

Mouse models are useful tool for carcinogenic study. They will greatly enrich the understanding of pathogenesis and molecular mechanisms for gastric cancer. However, only few of mice could develop gastric cancer spontaneously. With the development and improvement of gene transfer technology, investigators created a variety of transgenic and knockout/knockin mouse models of gastric cancer, such as INS-GAS mice and gastrin knockout mice. Combined with helicobacter infection and carcinogens treatment, these transgenic/knockout/knockin mice developed precancerous or cancerous lesions, which are proper for gene function study or experimental therapy. Here we review the progression of genetically engineered mouse models on gastric cancer research, and emphasize the effects of chemical carcinogens or infectious factors on carcinogenesis of genetically modified mouse. We also emphasize the histological examination on mouse stomach. We expect to provide researchers with some inspirations on this field. PMID:27713138

Genetically Modified Food in Perspective: An Inquiry-Based Curriculum to Help Middle School Students Make Sense of Tradeoffs. Research Report

ERIC Educational Resources Information Center

Seethaler, Sherry; Linn, Marcia

2004-01-01

To understand how students learn about science controversy, this study examines students' reasoning about tradeoffs in the context of a technology-enhanced curriculum about genetically modified food. The curriculum was designed and refined based on the Scaffolded Knowledge Integration Framework to help students sort and integrate their initial…

Awareness and support of release of genetically modified "sterile" mosquitoes, Key West, Florida, USA.

PubMed

Ernst, Kacey C; Haenchen, Steven; Dickinson, Katherine; Doyle, Michael S; Walker, Kathleen; Monaghan, Andrew J; Hayden, Mary H

2015-02-01

After a dengue outbreak in Key West, Florida, during 2009-2010, authorities, considered conducting the first US release of male Aedes aegypti mosquitoes genetically modified to prevent reproduction. Despite outreach and media attention, only half of the community was aware of the proposal; half of those were supportive. Novel public health strategies require community engagement.

Efficacy of genetically modified Bt toxins alone and in combinations against pink bollworm resistant to Cry1Ac and Cry2Ab

USDA-ARS?s Scientific Manuscript database

Evolution of resistance in pests threatens the long-term success of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Previous work showed that genetically modified Bt toxins Cry1AbMod and Cry1AcMod effectively countered resistance to native Bt toxins Cry1Ab and ...

The Development and Validation of the GMOAS, an Instrument Measuring Secondary School Students' Attitudes towards Genetically Modified Organisms

ERIC Educational Resources Information Center

Herodotou, Christothea; Kyza, Eleni A.; Nicolaidou, Iolie; Hadjichambis, Andreas; Kafouris, Dimitris; Terzian, Freda

2012-01-01

Genetically modified organisms (GMOs) is a rapidly evolving area of scientific innovation and an issue receiving global attention. Attempts to devise usable instruments that assess people's attitudes towards this innovation have been rare and non-systematic. The aim of this paper is to present the development and validation of the genetically…

Three-generation reproduction toxicity study of genetically modified rice with insect resistant genes.

PubMed

Hu, Yichun; Zhuo, Qin; Gong, Zhaolong; Piao, Jianhua; Yang, Xiaoguang

2017-01-01

In the present work, we evaluated the three generation reproductive toxicity of the genetically modified rice with insectresistant cry1Ac and sck genes. 120 Sprague-Dawley (SD) rats were divided into three groups which were fed with genetically modified rice diet (GM group), parental control rice diet (PR group) and AIN-93 control diet (both used as negative control) respectively. Bodyweight, food consumption, reproductive data, hematological parameters, serum chemistry, relative organ weights and histopathology for each generation were examined respectively. All the hematology and serum chemistry parameters, organ/body weight indicators were within the normal range or no change to the adverse direction was observed, although several differences in hematology and serum chemistry parameters (WBC, BUN, LDH of male rat, PLT, PCT, MPV of female rats), reproductive data (rate of morphologically abnormal sperm) were observed between GM rice group and two control groups. No macroscopic or histological adverse effects were found or considered as treatment-related, either. Overall, the three generation study of genetically modified rice with cry1Ac and sck genes at a high level showed no unintended adverse effects on rats's reproductive system. Copyright © 2016. Published by Elsevier Ltd.

Preliminary assessment of framework conditions for release of genetically modified mosquitoes in Burkina Faso.

PubMed

De Freece, Chenoa; Paré Toé, Léa; Esposito, Fulvio; Diabaté, Abdoulaye; Favia, Guido

2014-09-01

Genetically modified mosquitoes (GMMs) are emerging as a measure to control mosquito-borne diseases, but before any genetically modified organisms (GMOs) are released into the environment, it is imperative to establish regulatory standards incorporating public engagement. A previous project in Burkina Faso introduced a type of genetically modified cotton [Bacillus thuringiensis (Bt)] cotton) that produces insecticide, and incorporated policies on public engagement. We explored the perspectives of Burkinabè (citizens of Burkina Faso) on bio-agricultural exposure to GMOs and their receptiveness to the use of GMOs. Interviews were conducted in a village (Bondoukuy) and with representatives from stakeholder organizations. The population may be very receptive to the use of GMMs against malaria, but may voice unfounded concerns that GMMs can transmit other diseases. It is important to constantly supply the population with correct and factual information. Investigating the application of Burkina Faso's biotechnology policies with regard to Bt cotton has shown that it may be conceivable in the future to have open discussions about the merits of GMM release. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

PubMed

Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

2013-12-15

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

Low genetic diversity and strong population structure shaped by anthropogenic habitat fragmentation in a critically endangered primate, Trachypithecus leucocephalus.

PubMed

Wang, W; Qiao, Y; Li, S; Pan, W; Yao, M

2017-06-01

Habitat fragmentation may strongly impact population genetic structure and reduce the genetic diversity and viability of small and isolated populations. The white-headed langur (Trachypithecus leucocephalus) is a critically endangered primate species living in a highly fragmented and human-modified habitat in southern China. We examined the population genetic structure and genetic diversity of the species and investigated the environmental and anthropogenic factors that may have shaped its population structure. We used 214 unique multi-locus genotypes from 41 social groups across the main distribution area of T. leucocephalus, and found strong genetic structure and significant genetic differentiation among local populations. Our landscape genetic analyses using a causal modelling framework suggest that a large habitat gap and geographical distance represent the primary landscape elements shaping genetic structure, yet high levels of genetic differentiation also exist between patches separated by a small habitat gap or road. This is the first comprehensive study that has evaluated the population genetic structure and diversity of T. leucocephalus using nuclear markers. Our results indicate strong negative impacts of anthropogenic land modifications and habitat fragmentation on primate genetic connectivity between forest patches. Our analyses suggest that two management units of the species could be defined, and indicate that habitat continuity should be enforced and restored to reduce genetic isolation and enhance population viability.

Metabolomics of Genetically Modified Crops

PubMed Central

Simó, Carolina; Ibáñez, Clara; Valdés, Alberto; Cifuentes, Alejandro; García-Cañas, Virginia

2014-01-01

Metabolomic-based approaches are increasingly applied to analyse genetically modified organisms (GMOs) making it possible to obtain broader and deeper information on the composition of GMOs compared to that obtained from traditional analytical approaches. The combination in metabolomics of advanced analytical methods and bioinformatics tools provides wide chemical compositional data that contributes to corroborate (or not) the substantial equivalence and occurrence of unintended changes resulting from genetic transformation. This review provides insight into recent progress in metabolomics studies on transgenic crops focusing mainly in papers published in the last decade. PMID:25334064

Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models

PubMed Central

Fujihara, Yoshitaka; Miyata, Haruhiko; Ikawa, Masahito

2018-01-01

Mammalian fertilization is comprised of many steps including sperm survival in the uterus, sperm migration in the female reproductive tract, physiological and morphological changes to the spermatozoa, and sperm-egg interaction in the oviduct. In vitro studies have revealed essential factors for these fertilization steps for over half a century. However, the molecular mechanism of fertilization has recently been revised by the emergence of genetically modified animals. Here, we focus on essential factors for sperm fertilizing ability and describe recent advances in our knowledge of the mechanisms of mammalian fertilization, especially of sperm migration from the uterus into the oviduct. PMID:29353867

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders.

PubMed

Matrov, Denis; Kaart, Tanel; Lanfumey, Laurence; Maldonado, Rafael; Sharp, Trevor; Tordera, Rosa M; Kelly, Paul A; Deakin, Bill; Harro, Jaanus

2018-06-07

The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT 1 -/+ ), full knockout of the cannabinoid 1 receptor (CB1 -/- ), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of inter-regional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetically modified plants and food hypersensitivity diseases: usage and implications of experimental models for risk assessment.

PubMed

Prescott, Vanessa E; Hogan, Simon P

2006-08-01

The recent advances in biotechnology in the plant industry have led to increasing crop production and yield that in turn has increased the usage of genetically modified (GM) food in the human food chain. The usage of GM foods for human consumption has raised a number of fundamental questions including the ability of GM foods to elicit potentially harmful immunological responses, including allergic hypersensitivity. To assess the safety of foods derived from GM plants including allergenic potential, the US FDA, Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO), and the EU have developed approaches for evaluation assessment. One assessment approach that has been a very active area of research and debate is the development and usage of animal models to assess the potential allergenicity of GM foods. A number of specific animal models employing rodents, pigs, and dogs have been developed for allergenicity assessment. However, validation of these models is needed and consideration of the criteria for an appropriate animal model for the assessment of allergenicity in GM plants is required. We have recently employed a BALB/c mouse model to assess the potential allergenicity of GM plants. We have been able to demonstrate that this model is able to detect differences in antigenicity and identify aspects of protein post-translational modifications that can alter antigenicity. Furthermore, this model has also enabled us to examine the usage of GM plants as a therapeutic approach for the treatment of allergic diseases. This review discusses the current approaches to assess the allergenic potential of GM food and particularly focusing on the usage of animal models to determine the potential allergenicity of GM foods and gives an overview of our recent findings and implications of these studies.

Genetically modified soybeans and food allergies.

PubMed

Herman, Eliot M

2003-05-01

Allergenic reactions to proteins expressed in GM crops has been one of the prominent concerns among biotechnology critics and a concern of regulatory agencies. Soybeans like many plants have intrinsic allergens that present problems for sensitive people. Current GM crops, including soybean, have not been shown to add any additional allergenic risk beyond the intrinsic risks already present. Biotechnology can be used to characterize and eliminate allergens naturally present in crops. Biotechnology has been used to remove a major allergen in soybean demonstrating that genetic modification can be used to reduce allergenicity of food and feed. This provides a model for further use of GM approaches to eliminate allergens.

BIOTECHNOLOGY/ECORISK

EPA Science Inventory

This research effort is designed to provide the risk assessment community with modern genetic tools for evaluating long-term risks of genetically modified (GM) crops. Molecular population genetic data can potentially reveal information about long-term trends in both pest populat...

From Novice to Seasoned Practitioner: a Qualitative Investigation of Genetic Counselor Professional Development.

PubMed

Zahm, Kimberly Wehner; Veach, Patricia McCarthy; Martyr, Meredith A; LeRoy, Bonnie S

2016-08-01

Research on genetic counselor professional development would characterize typical developmental processes, inform training and supervision, and promote life-long development opportunities. To date, however no studies have comprehensively examined this phenomenon. The aims of this study were to investigate the nature of professional development for genetic counselors (processes, influences, and outcomes) and whether professional development varies across experience levels. Thirty-four genetic counselors participated in semi-structured telephone interviews exploring their perspectives on their professional development. Participants were sampled from three levels of post-degree genetic counseling experience: novice (0-5 years), experienced (6-14 years), and seasoned (>15 years). Using modified Consensual Qualitative Research and grounded theory methods, themes, domains, and categories were extracted from the data. The themes reflect genetic counselors' evolving perceptions of their professional development and its relationship to: (a) being a clinician, (b) their professional identity, and (c) the field itself. Across experience levels, prevalent influences on professional development were interpersonal (e.g., experiences with patients, genetic counseling colleagues) and involved professional and personal life events. Common developmental experiences included greater confidence and less anxiety over time, being less information-driven and more emotion-focused with patients, delivering "bad news" to patients remains challenging, and individuals' professional development experiences parallel genetic counseling's development as a field. With a few noteworthy exceptions, professional development was similar across experience levels. A preliminary model of genetic counselor professional development is proposed suggesting development occurs in a non-linear fashion throughout the professional lifespan. Each component of the model mutually influences the others, and there are positive and negative avenues of development.

Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

PubMed Central

Aviran, Sharon; Shah, Priya S.; Schaffer, David V.; Arkin, Adam P.

2010-01-01

Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents. PMID:20711350

Analytical criteria for performance characteristics of IgE binding methods for evaluating safety of biotech food products.

PubMed

Holzhauser, Thomas; Ree, Ronald van; Poulsen, Lars K; Bannon, Gary A

2008-10-01

There is detailed guidance on how to perform bioinformatic analyses and enzymatic degradation studies for genetically modified crops under consideration for approval by regulatory agencies; however, there is no consensus in the scientific community on the details of how to perform IgE serum studies. IgE serum studies are an important safety component to acceptance of genetically modified crops when the introduced protein is novel, the introduced protein is similar to known allergens, or the crop is allergenic. In this manuscript, we describe the characteristics of the reagents, validation of assay performance, and data analysis necessary to optimize the information obtained from serum testing of novel proteins and genetically modified (GM) crops and to make results more accurate and comparable between different investigations.

Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust.

PubMed

Bamford, K B; Wood, S; Shaw, R J

2005-02-01

Conducting gene therapy clinical trials with genetically modified organisms as the vectors presents unique safety and infection control issues. The area is governed by a range of legislation and guidelines, some unique to this field, as well as those pertinent to any area of clinical work. The relevant regulations covering gene therapy using genetically modified vectors are reviewed and illustrated with the approach taken by a large teaching hospital NHS Trust. Key elements were Trust-wide communication and involvement of staff in a pro-active approach to risk management, with specific emphasis on staff training and engagement, waste management, audit and record keeping. This process has led to the development of proposed standards for clinical trials involving genetically modified micro-organisms.

Use of Traditional and Genetically Modified Probiotics in Human Health: What Does the Future Hold?

PubMed

Bermúdez-Humarán, Luis G; Langella, Philippe

2017-09-01

Probiotics are live, nonpathogenic microorganisms that confer benefits to human health when administered in adequate amounts. Among the frequent proposed health benefits attributed to probiotics, their ability to interact with the host immune system is now well demonstrated. Although history has revealed that probiotics were part of fermented foods in the past, clinicians have started to use them therapeutically in regular diets. Moreover, the use of genetically modified probiotics to deliver molecules of therapeutic interest is gaining importance as an extension of the probiotic concept. This chapter summarizes some of the recent findings and perspectives on the use of both traditional and genetically modified probiotics to treat human diseases as well as what the future may hold concerning the use of these probiotics in humans.

[Labeling of food containing genetically modified organisms: international policies and Brazilian legislation].

PubMed

Costa, Thadeu Estevam Moreira Maramaldo; Marin, Victor Augustus

2011-08-01

The increase in surface area planted with genetically modified crops, with the subsequent transfer of such crops into the general environment for commercial trade, has raised questions about the safety of these products. The introduction of the Cartagena Protocol on Biosafety has led to the need to produce information and ensure training in this area for the implementation of policies on biosafety and for decision-making on the part of governments at the national, regional and international level. This article presents two main standpoints regarding the labeling of GM products (one adopted by the United States and the other by the European Union), as well as the position adopted by Brazil and its current legislation on labeling and commercial release of genetically modified (GM) products.

Environmental enrichment imparts disease-modifying and transgenerational effects on genetically-determined epilepsy and anxiety.

PubMed

Dezsi, Gabi; Ozturk, Ezgi; Salzberg, Michael R; Morris, Margaret; O'Brien, Terence J; Jones, Nigel C

2016-09-01

The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Environmental enrichment produces disease-modifying effects on genetically determined absence epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for genetically determined epilepsy which may benefit subsequent generations. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic Modifiers of Ovarian Cancer

DTIC Science & Technology

2014-08-01

samples from many countries. To account for population stratification, the genotyping data in combination with HapMap data (CEU, Yoruban, Han Chinese...Cambridge, we evaluated associations with both breast and ovarian cancer using a retrospective likelihood model. This accounts for the age extremes of...carriers we used a competing risk analysis that accounted for the effects on breast and ovarian cancer in parallel. In this competing risk analysis

Generation of gene-targeted mice using embryonic stem cells derived from a transgenic mouse model of Alzheimer's disease.

PubMed

Yamamoto, Satoshi; Ooshima, Yuki; Nakata, Mitsugu; Yano, Takashi; Matsuoka, Kunio; Watanabe, Sayuri; Maeda, Ryouta; Takahashi, Hideki; Takeyama, Michiyasu; Matsumoto, Yoshio; Hashimoto, Tadatoshi

2013-06-01

Gene-targeting technology using mouse embryonic stem (ES) cells has become the "gold standard" for analyzing gene functions and producing disease models. Recently, genetically modified mice with multiple mutations have increasingly been produced to study the interaction between proteins and polygenic diseases. However, introduction of an additional mutation into mice already harboring several mutations by conventional natural crossbreeding is an extremely time- and labor-intensive process. Moreover, to do so in mice with a complex genetic background, several years may be required if the genetic background is to be retained. Establishing ES cells from multiple-mutant mice, or disease-model mice with a complex genetic background, would offer a possible solution. Here, we report the establishment and characterization of novel ES cell lines from a mouse model of Alzheimer's disease (3xTg-AD mouse, Oddo et al. in Neuron 39:409-421, 2003) harboring 3 mutated genes (APPswe, TauP301L, and PS1M146V) and a complex genetic background. Thirty blastocysts were cultured and 15 stable ES cell lines (male: 11; female: 4) obtained. By injecting these ES cells into diploid or tetraploid blastocysts, we generated germline-competent chimeras. Subsequently, we confirmed that F1 mice derived from these animals showed similar biochemical and behavioral characteristics to the original 3xTg-AD mice. Furthermore, we introduced a gene-targeting vector into the ES cells and successfully obtained gene-targeted ES cells, which were then used to generate knockout mice for the targeted gene. These results suggest that the present methodology is effective for introducing an additional mutation into mice already harboring multiple mutated genes and/or a complex genetic background.

Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study.

PubMed

Poveda, Alaitz; Koivula, Robert W; Ahmad, Shafqat; Barroso, Inês; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Franks, Paul W

2016-03-01

We compared the ability of genetic (established type 2 diabetes, fasting glucose, 2 h glucose and obesity variants) and modifiable lifestyle (diet, physical activity, smoking, alcohol and education) risk factors to predict incident type 2 diabetes and obesity in a population-based prospective cohort of 3,444 Swedish adults studied sequentially at baseline and 10 years later. Multivariable logistic regression analyses were used to assess the predictive ability of genetic and lifestyle risk factors on incident obesity and type 2 diabetes by calculating the AUC. The predictive accuracy of lifestyle risk factors was similar to that yielded by genetic information for incident type 2 diabetes (AUC 75% and 74%, respectively) and obesity (AUC 68% and 73%, respectively) in models adjusted for age, age(2) and sex. The addition of genetic information to the lifestyle model significantly improved the prediction of type 2 diabetes (AUC 80%; p = 0.0003) and obesity (AUC 79%; p < 0.0001) and resulted in a net reclassification improvement of 58% for type 2 diabetes and 64% for obesity. These findings illustrate that lifestyle and genetic information separately provide a similarly high degree of long-range predictive accuracy for obesity and type 2 diabetes.

Application of synthetic biology in cyanobacteria and algae

PubMed Central

Wang, Bo; Wang, Jiangxin; Zhang, Weiwen; Meldrum, Deirdre R.

2012-01-01

Cyanobacteria and algae are becoming increasingly attractive cell factories for producing renewable biofuels and chemicals due to their ability to capture solar energy and CO2 and their relatively simple genetic background for genetic manipulation. Increasing research efforts from the synthetic biology approach have been made in recent years to modify cyanobacteria and algae for various biotechnological applications. In this article, we critically review recent progresses in developing genetic tools for characterizing or manipulating cyanobacteria and algae, the applications of genetically modified strains for synthesizing renewable products such as biofuels and chemicals. In addition, the emergent challenges in the development and application of synthetic biology for cyanobacteria and algae are also discussed. PMID:23049529

Application of laws, policies, and guidance from the United States and Canada to the regulation of food and feed derived from genetically modified crops: interpretation of composition data.

PubMed

Price, William D; Underhill, Lynne

2013-09-04

With the development of recombinant DNA techniques for genetically modifying plants to exhibit beneficial traits, laws and regulations were adopted to ensure the safety of food and feed derived from such plants. This paper focuses on the regulation of genetically modified (GM) plants in Canada and the United States, with emphasis on the results of the compositional analysis routinely utilized as an indicator of possible unintended effects resulting from genetic modification. This work discusses the mandate of Health Canada and the Canadian Food Inspection Agency as well as the U.S. Food and Drug Administration's approach to regulating food and feed derived from GM plants. This work also addresses how publications by the Organisation for Economic Co-operation and Development and Codex Alimentarius fit, particularly with defining the importance and purpose of compositional analysis. The importance of study design, selection of comparators, use of literature, and commercial variety reference values is also discussed.

Specificity redirection by CAR with human VEGFR-1 affinity endows T lymphocytes with tumor-killing ability and anti-angiogenic potency.

PubMed

Wang, W; Ma, Y; Li, J; Shi, H-S; Wang, L-Q; Guo, F-C; Zhang, J; Li, D; Mo, B-H; Wen, F; Liu, T; Liu, Y-T; Wang, Y-S; Wei, Y-Q

2013-10-01

Immunotherapy that is based on adoptive transfer of T lymphocytes, which are genetically modified to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens, has been demonstrated to be an efficient cancer therapy. Vascular endothelial growth factor receptor-1 (VEGFR-1), a vital molecule involved in tumor growth and angiogenesis, has not been targeted by CAR-modified T lymphocytes. In this study, we generated CAR-modified T lymphocytes with human VEGFR-1 specificity (V-1 CAR) by electroporation. V-1 CAR-modified T lymphocytes were demonstrated to elicit lytic cytotoxicity to target cells in a VEGFR-1-dependent manner. The adoptive transfer of V-1 CAR T lymphocytes delayed tumor growth and formation and inhibited pulmonary metastasis in xenograft models and such efficacies were enhanced by cotransfer of T lymphocytes that expressed interleukin-15 (IL-15). Moreover, V-1 CAR-modified T lymphocytes lysed primary endothelial cells and impaired tube formation, in vitro. These data demonstrated the antitumor and anti-angiogenesis ability of V-1 CAR-modified T lymphocytes. Our study provides the rationale for the clinical translation of CAR-modified T lymphocytes with VEGFR-1 specificity.

Powerful multilocus tests of genetic association in the presence of gene-gene and gene-environment interactions.

PubMed

Chatterjee, Nilanjan; Kalaylioglu, Zeynep; Moslehi, Roxana; Peters, Ulrike; Wacholder, Sholom

2006-12-01

In modern genetic epidemiology studies, the association between the disease and a genomic region, such as a candidate gene, is often investigated using multiple SNPs. We propose a multilocus test of genetic association that can account for genetic effects that might be modified by variants in other genes or by environmental factors. We consider use of the venerable and parsimonious Tukey's 1-degree-of-freedom model of interaction, which is natural when individual SNPs within a gene are associated with disease through a common biological mechanism; in contrast, many standard regression models are designed as if each SNP has unique functional significance. On the basis of Tukey's model, we propose a novel but computationally simple generalized test of association that can simultaneously capture both the main effects of the variants within a genomic region and their interactions with the variants in another region or with an environmental exposure. We compared performance of our method with that of two standard tests of association, one ignoring gene-gene/gene-environment interactions and the other based on a saturated model of interactions. We demonstrate major power advantages of our method both in analysis of data from a case-control study of the association between colorectal adenoma and DNA variants in the NAT2 genomic region, which are well known to be related to a common biological phenotype, and under different models of gene-gene interactions with use of simulated data.

Radial Domany-Kinzel models with mutation and selection

NASA Astrophysics Data System (ADS)

Lavrentovich, Maxim O.; Korolev, Kirill S.; Nelson, David R.

2013-01-01

We study the effect of spatial structure, genetic drift, mutation, and selective pressure on the evolutionary dynamics in a simplified model of asexual organisms colonizing a new territory. Under an appropriate coarse-graining, the evolutionary dynamics is related to the directed percolation processes that arise in voter models, the Domany-Kinzel (DK) model, contact process, and so on. We explore the differences between linear (flat front) expansions and the much less familiar radial (curved front) range expansions. For the radial expansion, we develop a generalized, off-lattice DK model that minimizes otherwise persistent lattice artifacts. With both simulations and analytical techniques, we study the survival probability of advantageous mutants, the spatial correlations between domains of neutral strains, and the dynamics of populations with deleterious mutations. “Inflation” at the frontier leads to striking differences between radial and linear expansions. For a colony with initial radius R0 expanding at velocity v, significant genetic demixing, caused by local genetic drift, occurs only up to a finite time t*=R0/v, after which portions of the colony become causally disconnected due to the inflating perimeter of the expanding front. As a result, the effect of a selective advantage is amplified relative to genetic drift, increasing the survival probability of advantageous mutants. Inflation also modifies the underlying directed percolation transition, introducing novel scaling functions and modifications similar to a finite-size effect. Finally, we consider radial range expansions with deflating perimeters, as might arise from colonization initiated along the shores of an island.

Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain.

PubMed

Sun, Yi; Tian, Yuke; Li, Haifeng; Zhang, Dengwen; Sun, Qiang

2017-01-01

Background . This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model. Methods . Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 10 6 ) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results . No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1 β and IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion . The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.

A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency.

PubMed

O'Reilly, Linda P; Long, Olivia S; Cobanoglu, Murat C; Benson, Joshua A; Luke, Cliff J; Miedel, Mark T; Hale, Pamela; Perlmutter, David H; Bahar, Ivet; Silverman, Gary A; Pak, Stephen C

2014-10-01

α1-Antitrypsin deficiency (ATD) is a common genetic disorder that can lead to end-stage liver and lung disease. Although liver transplantation remains the only therapy currently available, manipulation of the proteostasis network (PN) by small molecule therapeutics offers great promise. To accelerate the drug-discovery process for this disease, we first developed a semi-automated high-throughput/content-genome-wide RNAi screen to identify PN modifiers affecting the accumulation of the α1-antitrypsin Z mutant (ATZ) in a Caenorhabditis elegans model of ATD. We identified 104 PN modifiers, and these genes were used in a computational strategy to identify human ortholog-ligand pairs. Based on rigorous selection criteria, we identified four FDA-approved drugs directed against four different PN targets that decreased the accumulation of ATZ in C. elegans. We also tested one of the compounds in a mammalian cell line with similar results. This methodology also proved useful in confirming drug targets in vivo, and predicting the success of combination therapy. We propose that small animal models of genetic disorders combined with genome-wide RNAi screening and computational methods can be used to rapidly, economically and strategically prime the preclinical discovery pipeline for rare and neglected diseases with limited therapeutic options. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Managing major data of genetically modified mice: from scientific demands to legal obligations.

PubMed

Staudt, Michael; Trauth, Jürgen; Hindi, Iris El; Galuschka, Claudia; Sitek, Dagmar; Schenkel, Johannes

2012-10-01

The number of genetically modified mice is increasing rapidly. Several limitations when working with these animals are to be considered: small colonies, the continued danger of loss, often a limited breeding-success, the need to keep those mutants in stock, difficult and costly import-procedures, and also a major (scientific) value of those mutants often available only with major restrictions. To gather relevant information about all active and archived genetically modified mouse lines available in-house (>1.500) and to deal with a unique resource for several, quite different purposes, a data base was developed enabling optimum knowledge management and easy access. The data base covers also legal restraints and is being linked with the institutional publication repository. To identify the lines available detailed information is provided for each line, as the international designation, a short name, the characterization/description, and the genetic modification including the technique used therefore. The origin of the mutation (gene-ID# and donor organism), the origin of regulatory elements and their donors are listed as well as the genetic background, back-cross generation, phenotype, possible publications, keywords, and some in-house information. Also aspects of animal welfare, obligations to record genetically modified organisms, and technology transfer are displayed; the latter to make licenses possible (if legally permitted). Material transfer agreements, patents, or legal restrictions are listed. This data base helps to avoid double-imports, saves animals and costs since a redundant generation or import can be omitted. However, this is a contribution to the 3R principles developed by Russell and Burch.

Genetically modified foods and social concerns.

PubMed

Maghari, Behrokh Mohajer; Ardekani, Ali M

2011-07-01

Biotechnology is providing us with a wide range of options for how we can use agricultural and commercial forestry lands. The cultivation of genetically modified (GM) crops on millions of hectares of lands and their injection into our food chain is a huge global genetic experiment involving all living beings. Considering the fast pace of new advances in production of genetically modified crops, consumers, farmers and policymakers worldwide are challenged to reach a consensus on a clear vision for the future of world food supply. The current food biotechnology debate illustrates the serious conflict between two groups: 1) Agri-biotech investors and their affiliated scientists who consider agricultural biotechnology as a solution to food shortage, the scarcity of environmental resources and weeds and pests infestations; and 2) independent scientists, environmentalists, farmers and consumers who warn that genetically modified food introduces new risks to food security, the environment and human health such as loss of biodiversity; the emergence of superweeds and superpests; the increase of antibiotic resistance, food allergies and other unintended effects. This article reviews major viewpoints which are currently debated in the food biotechnology sector in the world. It also lays the ground-work for deep debate on benefits and risks of Biotech-crops for human health, ecosystems and biodiversity. In this context, although some regulations exist, there is a need for continuous vigilance for all countries involved in producing genetically engineered food to follow the international scientific bio-safety testing guidelines containing reliable pre-release experiments and post-release track of transgenic plants to protect public health and avoid future environmental harm.

Awareness and Support of Release of Genetically Modified “Sterile” Mosquitoes, Key West, Florida, USA

PubMed Central

Haenchen, Steven; Dickinson, Katherine; Doyle, Michael S.; Walker, Kathleen; Monaghan, Andrew J.; Hayden, Mary H.

2015-01-01

After a dengue outbreak in Key West, Florida, during 2009–2010, authorities, considered conducting the first US release of male Aedes aegypti mosquitoes genetically modified to prevent reproduction. Despite outreach and media attention, only half of the community was aware of the proposal; half of those were supportive. Novel public health strategies require community engagement. PMID:25625795

Physical activity modifies the associations between genetic variants and blood pressure in European adolescents.

PubMed

de Moraes, Augusto César Ferreira; Fernández-Alvira, Juan Miguel; Carvalho, Heráclito Barbosa; Meirhaeghe, Aline; Dallongeville, Jean; Kafatos, Anthony; Marcos, Ascensión; Molnar, Dénes; Manios, Yannis; Ruiz, Jonatan R; Labayen, Idoia; Widhalm, Kurt; Breidenassel, Christina; Gonzalez-Gróss, Marcela; Moreno, Luis A

2014-11-01

We hypothesized that physical activity and sedentary behavior could modify the associations between known genetic variants blood pressure-associated genes in European adolescents. Meeting current physical activity recommendations (≥ 60 minutes/day) was able attenuate the deleterious effect of the NOS3 rs3918227 polymorphism on systolic blood pressure in European adolescents. Copyright © 2014 Elsevier Inc. All rights reserved.

Knowledge of, Attitudes toward, and Acceptance of Genetically Modified Organisms among Prospective Teachers of Biology, Home Economics, and Grade School in Slovenia

ERIC Educational Resources Information Center

Sorgo, Andrej; Ambrozic-Dolinsek, Jana

2010-01-01

The objective of this study was to investigate knowledge, opinions, and attitudes toward, as well as readiness to accept genetically modified organisms (GMOs) among prospective primary and secondary Slovene teachers. Our findings are that prospective teachers want to take an active role in rejecting or supporting individual GMOs and are aware of…

The Effects of Different Types of Text and Individual Differences on View Complexity about Genetically Modified Organisms

ERIC Educational Resources Information Center

Dinsmore, Daniel L.; Zoellner, Brian P.; Parkinson, Meghan M.; Rossi, Anthony M.; Monk, Mary J.; Vinnachi, Jenelle

2017-01-01

View change about socio-scientific issues has been well studied in the literature, but the change in the complexity of those views has not. In the current study, the change in the complexity of views about a specific scientific topic (i.e. genetically modified organisms; GMOs) and use of evidence in explaining those views was examined in relation…

Basic-Education Mexican Teachers' Knowledge of Biotechnology and Attitudes about the Consumption of Genetically Modified Foods

ERIC Educational Resources Information Center

Jiménez-Salas, Zacarías; Campos-Góngora, Eduardo; González-Martínez, Blanca E.; Tijerina-Sáenz, Alexandra; Escamilla-Méndez, Angélica D.; Ramírez-López, Erik

2017-01-01

Over the past few years, a new research field has emerged, focusing on the social-scientific criteria for the study of opinions toward genetically modified foods (GMFs), since these may be limiting factors for the success or failure of these products. Basic education is the first step in the Mexican education system, and teachers may wield an…

An Improved System for Generation of Diploid Cloned Porcine Embryos Using Induced Pluripotent Stem Cells Synchronized to Metaphase.

PubMed

Kim, Eunhye; Zheng, Zhong; Jeon, Yubyeol; Jin, Yong-Xun; Hwang, Seon-Ung; Cai, Lian; Lee, Chang-Kyu; Kim, Nam-Hyung; Hyun, Sang-Hwan

2016-01-01

Pigs provide outstanding models of human genetic diseases due to their striking similarities with human anatomy, physiology and genetics. Although transgenic pigs have been produced using genetically modified somatic cells and nuclear transfer (SCNT), the cloning efficiency was extremely low. Here, we report an improved method to produce diploid cloned embryos from porcine induced pluripotent stem cells (piPSCs), which were synchronized to the G2/M stage using a double blocking method with aphidicolin and nocodazole. The efficiency of this synchronization method on our piPSC lines was first tested. Then, we modified our traditional SCNT protocol to find a workable protocol. In particular, the removal of a 6DMAP treatment post-activation enhanced the extrusion rate of pseudo-second-polar bodies (p2PB) (81.3% vs. 15.8%, based on peak time, 4hpa). Moreover, an immediate activation method yielded significantly more blastocysts than delayed activation (31.3% vs. 16.0%, based on fused embryos). The immunofluorescent results confirmed the effect of the 6DMAP treatment removal, showing remarkable p2PB extrusion during a series of nuclear transfer procedures. The reconstructed embryos from metaphase piPSCs with our modified protocol demonstrated normal morphology at 2-cell, 4-cell and blastocyst stages and a high rate of normal karyotype. This study demonstrated a new and efficient way to produce viable cloned embryos from piPSCs when synchronized to the G2/M phase of the cell cycle, which may lead to opportunities to produce cloned pigs from piPSCs more efficiently.

Genetically modified crops and aquatic ecosystems: considerations for environmental risk assessment and non-target organism testing.

PubMed

Carstens, Keri; Anderson, Jennifer; Bachman, Pamela; De Schrijver, Adinda; Dively, Galen; Federici, Brian; Hamer, Mick; Gielkens, Marco; Jensen, Peter; Lamp, William; Rauschen, Stefan; Ridley, Geoff; Romeis, Jörg; Waggoner, Annabel

2012-08-01

Environmental risk assessments (ERA) support regulatory decisions for the commercial cultivation of genetically modified (GM) crops. The ERA for terrestrial agroecosystems is well-developed, whereas guidance for ERA of GM crops in aquatic ecosystems is not as well-defined. The purpose of this document is to demonstrate how comprehensive problem formulation can be used to develop a conceptual model and to identify potential exposure pathways, using Bacillus thuringiensis (Bt) maize as a case study. Within problem formulation, the insecticidal trait, the crop, the receiving environment, and protection goals were characterized, and a conceptual model was developed to identify routes through which aquatic organisms may be exposed to insecticidal proteins in maize tissue. Following a tiered approach for exposure assessment, worst-case exposures were estimated using standardized models, and factors mitigating exposure were described. Based on exposure estimates, shredders were identified as the functional group most likely to be exposed to insecticidal proteins. However, even using worst-case assumptions, the exposure of shredders to Bt maize was low and studies supporting the current risk assessments were deemed adequate. Determining if early tier toxicity studies are necessary to inform the risk assessment for a specific GM crop should be done on a case by case basis, and should be guided by thorough problem formulation and exposure assessment. The processes used to develop the Bt maize case study are intended to serve as a model for performing risk assessments on future traits and crops.

REGION-WIDE GENETIC STRUCTURE OF THE CENTRAL STONEROLLER (CAMPOSTOMA ANOMALUM) AND THE RELATIONSHIP OF GENETIC DIVERSITY TO ENVIRONMENTAL QUALITY

EPA Science Inventory

Anthropogenic stressors that reduce population size, alter migration corridors or modify mutational and selective forces on populations are expected to leave a lasting genetic footprint on the distribution of intraspecific genetic variation. Thus, the pattern of intraspecific gen...

Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: A female twin study

PubMed Central

Knopik, Valerie S.; Heath, Andrew C.; Bucholz, Kathleen K.; Madden, Pamela A.F.; Waldron, Mary

2009-01-01

Genetic and environmental contributions to the observed correlations among DSM-IV ADHD problems [inattentive (INATT) and hyperactive/impulsive (HYP/IMP) behaviors], conduct problems (CDP) and alcohol problems (AlcProb) were examined by fitting multivariate structural equation models to data from the Missouri Adolescent Female Twin Study [N=2892 twins (831 monozygotic pairs, 615 dizygotic pairs)]. Based on results of preliminary regression models, we modified the structural model to jointly estimate (i) the regression of each phenotype on significant familial/prenatal predictors, and (ii) genetic and environmental contributions to the residual variance and covariance. Results suggested that (i) parental risk factors, such as parental alcohol dependence and regular smoking, increase risk for externalizing behavior; (ii) prenatal exposures predicted increased symptomatology for HYP/IMP (smoking during pregnancy), INATT and CDP (prenatal alcohol exposure); (iii) after adjusting for measured familial/prenatal risk factors, genetic influences were significant for HYP/IMP, INATT, and CDP; however, similar to earlier reports, genetic effects on alcohol dependence symptoms were negligible; and (iv) in adolescence, correlated liabilities for conduct and alcohol problems are found in environmental factors common to both phenotypes, while covariation among impulsivity, inattention, and conduct problems is primarily due to genetic influences common to these three behaviors. Thus, while a variety of adolescent problem behaviors are significantly correlated, the structure of that association may differ as a function of phenotype (e.g., comorbid HYP/IMP and CDP vs. comorbid CDP and AlcProb), a finding that could inform different approaches to treatment and prevention. PMID:19341765

Sexual and apomictic plant reproduction in the genomics era: exploring the mechanisms potentially useful in crop plants.

PubMed

Dwivedi, Sangam L; Perotti, Enrico; Upadhyaya, Hari D; Ortiz, Rodomiro

2010-12-01

Arabidopsis, Mimulus and tomato have emerged as model plants in researching genetic and molecular basis of differences in mating systems. Variations in floral traits and loss of self-incompatibility have been associated with mating system differences in crops. Genomics research has advanced considerably, both in model and crop plants, which may provide opportunities to modify breeding systems as evidenced in Arabidopsis and tomato. Mating system, however, not recombination per se, has greater effect on the level of polymorphism. Generating targeted recombination remains one of the most important factors for crop genetic enhancement. Asexual reproduction through seeds or apomixis, by producing maternal clones, presents a tremendous potential for agriculture. Although believed to be under simple genetic control, recent research has revealed that apomixis results as a consequence of the deregulation of the timing of sexual events rather than being the product of specific apomixis genes. Further, forward genetic studies in Arabidopsis have permitted the isolation of novel genes reported to control meiosis I and II entry. Mutations in these genes trigger the production of unreduced or apomeiotic megagametes and are an important step toward understanding and engineering apomixis.

Cultural evolutionary theory: How culture evolves and why it matters

PubMed Central

Creanza, Nicole; Kolodny, Oren; Feldman, Marcus W.

2017-01-01

Human cultural traits—behaviors, ideas, and technologies that can be learned from other individuals—can exhibit complex patterns of transmission and evolution, and researchers have developed theoretical models, both verbal and mathematical, to facilitate our understanding of these patterns. Many of the first quantitative models of cultural evolution were modified from existing concepts in theoretical population genetics because cultural evolution has many parallels with, as well as clear differences from, genetic evolution. Furthermore, cultural and genetic evolution can interact with one another and influence both transmission and selection. This interaction requires theoretical treatments of gene–culture coevolution and dual inheritance, in addition to purely cultural evolution. In addition, cultural evolutionary theory is a natural component of studies in demography, human ecology, and many other disciplines. Here, we review the core concepts in cultural evolutionary theory as they pertain to the extension of biology through culture, focusing on cultural evolutionary applications in population genetics, ecology, and demography. For each of these disciplines, we review the theoretical literature and highlight relevant empirical studies. We also discuss the societal implications of the study of cultural evolution and of the interactions of humans with one another and with their environment. PMID:28739941

Cultural evolutionary theory: How culture evolves and why it matters.

PubMed

Creanza, Nicole; Kolodny, Oren; Feldman, Marcus W

2017-07-24

Human cultural traits-behaviors, ideas, and technologies that can be learned from other individuals-can exhibit complex patterns of transmission and evolution, and researchers have developed theoretical models, both verbal and mathematical, to facilitate our understanding of these patterns. Many of the first quantitative models of cultural evolution were modified from existing concepts in theoretical population genetics because cultural evolution has many parallels with, as well as clear differences from, genetic evolution. Furthermore, cultural and genetic evolution can interact with one another and influence both transmission and selection. This interaction requires theoretical treatments of gene-culture coevolution and dual inheritance, in addition to purely cultural evolution. In addition, cultural evolutionary theory is a natural component of studies in demography, human ecology, and many other disciplines. Here, we review the core concepts in cultural evolutionary theory as they pertain to the extension of biology through culture, focusing on cultural evolutionary applications in population genetics, ecology, and demography. For each of these disciplines, we review the theoretical literature and highlight relevant empirical studies. We also discuss the societal implications of the study of cultural evolution and of the interactions of humans with one another and with their environment.

Modeling Structure-Function Relationships in Synthetic DNA Sequences using Attribute Grammars

PubMed Central

Cai, Yizhi; Lux, Matthew W.; Adam, Laura; Peccoud, Jean

2009-01-01

Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part. This concept provides a finer level of granularity than the traditional notion of the gene. However, a method of formally relating how a set of parts relates to a function has not yet emerged. Synthetic biology both demands such a formalism and provides an ideal setting for testing hypotheses about relationships between DNA sequences and phenotypes beyond the gene-centric methods used in genetics. Attribute grammars are used in computer science to translate the text of a program source code into the computational operations it represents. By associating attributes with parts, modifying the value of these attributes using rules that describe the structure of DNA sequences, and using a multi-pass compilation process, it is possible to translate DNA sequences into molecular interaction network models. These capabilities are illustrated by simple example grammars expressing how gene expression rates are dependent upon single or multiple parts. The translation process is validated by systematically generating, translating, and simulating the phenotype of all the sequences in the design space generated by a small library of genetic parts. Attribute grammars represent a flexible framework connecting parts with models of biological function. They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts. This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology. PMID:19816554

Nature and nurture: environmental influences on a genetic rat model of depression

PubMed Central

Mehta-Raghavan, N S; Wert, S L; Morley, C; Graf, E N; Redei, E E

2016-01-01

In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or ‘nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, ‘trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms. PMID:27023176

Efficient Modification of the CCR5 Locus in Primary Human T Cells With megaTAL Nuclease Establishes HIV-1 Resistance

PubMed Central

Romano Ibarra, Guillermo S; Paul, Biswajit; Sather, Blythe D; Younan, Patrick M; Sommer, Karen; Kowalski, John P; Hale, Malika; Stoddard, Barry; Jarjour, Jordan; Astrakhan, Alexander; Kiem, Hans-Peter; Rawlings, David J

2016-01-01

A naturally occurring 32-base pair deletion of the HIV-1 co-receptor CCR5 has demonstrated protection against HIV infection of human CD4+ T cells. Recent genetic engineering approaches using engineered nucleases to disrupt the gene and mimic this mutation show promise for HIV therapy. We developed a megaTAL nuclease targeting the third extracellular loop of CCR5 that we delivered to primary human T cells by mRNA transfection. The CCR5 megaTAL nuclease established resistance to HIV in cell lines and disrupted the expression of CCR5 on primary human CD4+ T cells with a high efficiency, achieving up to 80% modification of the locus in primary cells as measured by molecular analysis. Gene-modified cells engrafted at levels equivalent to unmodified cells when transplanted into immunodeficient mice. Furthermore, genetically modified CD4+ cells were preferentially expanded during HIV-1 infection in vivo in an immunodeficient mouse model. Our results demonstrate the feasibility of targeting CCR5 in primary T cells using an engineered megaTAL nuclease, and the potential to use gene-modified cells to reconstitute a patient's immune system and provide protection from HIV infection. PMID:27741222

Dual targeting of gene delivery by genetic modification of adenovirus serotype 5 fibers and cell-selective transcriptional control.

PubMed

Work, L M; Ritchie, N; Nicklin, S A; Reynolds, P N; Baker, A H

2004-08-01

Adenovirus (Ad)-mediated gene delivery is a promising approach for genetic manipulation of the vasculature and is being used in both preclinical models and clinical trials. However, safety concerns relating to infection of nontarget tissue and the poor infectivity of vascular cells compared to other cell types necessitates Ad vector refinement. Here, we combine a transductional targeting approach to improve vascular cell infectivity through RGD peptide insertion into adenovirus fibers, combined with transcriptional targeting to endothelial cells using a approximately 1 kb fragment of the fms-like tyrosine kinase receptor-1 (FLT-1) promoter. Single- and double-modified vectors were characterized in human cell lines that either support or have silenced FLT-1 expression. In rat hepatocytes and endothelial cells, the double modification substantially shifted transduction profiles toward vascular endothelial cells. Furthermore, in intact aortae derived from spontaneously hypertensive rats that display enhanced alphav integrin expression on dysfunctional endothelium, enhanced levels of transduction were observed using the double-modified vector but not in aortae derived from normotensive control rats. Our data indicate that Ad-mediated transduction can be beneficially modified in vitro and in vivo by combining fiber modification and a cell-selective promoter within a single-component vector system.

Genetic modification of Anopheles stephensi for resistance to multiple Plasmodium falciparum strains does not influence susceptibility to o'nyong'nyong virus or insecticides, or Wolbachia-mediated resistance to the malaria parasite.

PubMed

Pike, Andrew; Dimopoulos, George

2018-01-01

Mosquitoes that have been genetically engineered for resistance to human pathogens are a potential new tool for controlling vector-borne disease. However, genetic modification may have unintended off-target effects that could affect the mosquitoes' utility for disease control. We measured the resistance of five genetically modified Plasmodium-suppressing Anopheles stephensi lines to o'nyong'nyong virus, four classes of insecticides, and diverse Plasmodium falciparum field isolates and characterized the interactions between our genetic modifications and infection with the bacterium Wolbachia. The genetic modifications did not alter the mosquitoes' resistance to either o'nyong'nyong virus or insecticides, and the mosquitoes were equally resistant to all tested P. falciparum strains, regardless of Wolbachia infection status. These results indicate that mosquitoes can be genetically modified for resistance to malaria parasite infection and remain compatible with other vector-control measures without becoming better vectors for other pathogens.

Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease

PubMed Central

Haas, Laura T.; Salazar, Santiago V.; Kostylev, Mikhail A.; Um, Ji Won; Kaufman, Adam C.

2016-01-01

Alzheimer’s disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer’s disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer’s disease transgenes or by human Alzheimer’s disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp–Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer’s disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer’s disease pathogenesis, and the complex is a potential target for disease-modifying intervention. PMID:26667279

Development and validation of a sensitive and fast chemiluminescent enzyme immunoassay for the detection of genetically modified maize.

PubMed

Roda, A; Mirasoli, M; Guardigli, M; Michelini, E; Simoni, P; Magliulo, M

2006-03-01

Proteins from the Cry 1 family, in particular Cry 1Ab, are commonly expressed in genetically modified Bt maize in order to control chewing insect pests. A sensitive chemiluminescent sandwich enzyme immunoassay for the detection of Cry1Ab protein from genetically modified Bt maize has been developed and validated. A Cry1Ab protein-specific antibody was immobilized on 96- or 384-well microtiter plates in order to capture the Cry1Ab toxin in the sample; the bound toxin was then detected by employing a second anti-Cry1Ab antibody and a horseradish peroxidase-labeled anti-antibody, followed by measurement of the enzyme activity with an enhanced chemiluminescent system. The chemiluminescent assay fulfilled all the requirements of accuracy and precision and exhibited limits of detection of a few pg mL(-1) Cry1Ab (3 or 5 pg mL(-1), depending on the assay format), which are significantly lower than that achievable using conventional colorimetric detection of peroxidase activity and also represent an improvement compared to previously developed Cry1Ab immunoassays. High-throughput analysis can be performed using the 384-well microtiter plate format immunoassay, which also allows one to reduce the consumption of samples and reagents. Validation of the assay, performed by analyzing certified reference materials, proved that the immunoassay is able to detect the presence of the Cry1Ab protein in certified reference samples containing as low as 0.1% of MON 810 genetically modified Bt maize. This value is below the threshold requiring mandatory labeling of foods containing genetically modified material according to the actual EU regulation.

Lipid production in association of filamentous fungi with genetically modified cyanobacterial cells.

PubMed

Miranda, Ana F; Taha, Mohamed; Wrede, Digby; Morrison, Paul; Ball, Andrew S; Stevenson, Trevor; Mouradov, Aidyn

2015-01-01

Numerous strategies have evolved recently for the generation of genetically modified or synthetic microalgae and cyanobacteria designed for production of ethanol, biodiesel and other fuels. In spite of their obvious attractiveness there are still a number of challenges that can affect their economic viability: the high costs associated with (1) harvesting, which can account for up to 50 % of the total biofuel's cost, (2) nutrients supply and (3) oil extraction. Fungal-assisted bio-flocculation of microalgae is gaining increasing attention due to its high efficiency, no need for added chemicals and low energy inputs. The implementation of renewable alternative carbon, nitrogen and phosphorus sources from agricultural wastes and wastewaters for growing algae and fungi makes this strategy economically attractive. This work demonstrates that the filamentous fungi, Aspergillus fumigatus can efficiently flocculate the unicellular cyanobacteria Synechocystis PCC 6803 and its genetically modified derivatives that have been altered to enable secretion of free fatty acids into growth media. Secreted free fatty acids are potentially used by fungal cells as a carbon source for growth and ex-novo production of lipids. For most of genetically modified strains the total lipid yields extracted from the fungal-cyanobacterial pellets were found to be higher than additive yields of lipids and total free fatty acids produced by fungal and Synechocystis components when grown in mono-cultures. The synergistic effect observed in fungal-Synechocystis associations was also found in bioremediation rates when animal husbandry wastewater was used an alternative source of nitrogen and phosphorus. Fungal assisted flocculation can complement and assist in large scale biofuel production from wild-type and genetically modified Synechocystis PCC 6803 strains by (1) efficient harvesting of cyanobacterial cells and (2) producing of high yields of lipids accumulated in fungal-cyanobacterial pellets.

Do genetic modifiers of high-density lipoprotein cholesterol and triglyceride levels also modify their response to a lifestyle intervention in the setting of obesity and type-2 diabetes mellitus?: The Action for Health in Diabetes (Look AHEAD) study.

PubMed

Huggins, Gordon S; Papandonatos, George D; Erar, Bahar; Belalcazar, L Maria; Brautbar, Ariel; Ballantyne, Christie; Kitabchi, Abbas E; Wagenknecht, Lynne E; Knowler, William C; Pownall, Henry J; Wing, Rena R; Peter, Inga; McCaffery, Jeanne M

2013-08-01

High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education. We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (P=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (P<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (P=0.0009). This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.

Do Genetic Modifiers of HDL-C and Triglyceride Levels also Modify Their Response to a Lifestyle Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus? The Look AHEAD Study

PubMed Central

Huggins, Gordon S.; Papandonatos, George D.; Erar, Bahar; Belalcazar, L. Maria; Brautbar, Ariel; Ballantyne, Christie; Kitabchi, Abbas E.; Wagenknecht, Lynne E.; Knowler, William C.; Pownall, Henry J.; Wing, Rena R.; Peter, Inga; McCaffery, Jeanne M.

2014-01-01

Background High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies (GWASs) as associated with HDL-C or triglyceride levels will modify 1-year treatment response to an intensive lifestyle intervention (ILI), relative to a usual care of diabetes support and education (DSE). Methods and Results We evaluated 82 SNPs, representing 31 loci demonstrated by GWAS to be associated with HDL-C and/or triglycerides, in 3,561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with ILI (p=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (p=0.047 and 0.046, respectively). The fatty acid desaturase-2 (FADS-2) rs1535 variant, associated with low baseline HDL-C (p=0.017), was associated with HDL-C increases with ILI (0.0037) and had a nominal treatment interaction (p= 0.035). ApoB (rs693) and LIPC (rs8034802) SNPs showed nominally significant associations with HDL-C and triglyceride changes with ILI and a treatment interaction (p<0.05). A PGS1 SNP (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (p=0.0009). Conclusions This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight/obese diabetic individuals. The effect of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention. PMID:23861364

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting

PubMed Central

Schulte, P. A.; Whittaker, C.; Curran, C. P.

2015-01-01

Risk assessment forms the basis for both occupational health decision-making and the development of occupational exposure limits (OELs). Although genetic and epigenetic data have not been widely used in risk assessment and ultimately, standard setting, it is possible to envision such uses. A growing body of literature demonstrates that genetic and epigenetic factors condition biological responses to occupational and environmental hazards or serve as targets of them. This presentation addresses the considerations for using genetic and epigenetic information in risk assessments, provides guidance on using this information within the classic risk assessment paradigm, and describes a framework to organize thinking about such uses. The framework is a 4 × 4 matrix involving the risk assessment functions (hazard identification, dose-response modeling, exposure assessment, and risk characterization) on one axis and inherited and acquired genetic and epigenetic data on the other axis. The cells in the matrix identify how genetic and epigenetic data can be used for each risk assessment function. Generally, genetic and epigenetic data might be used as endpoints in hazard identification, as indicators of exposure, as effect modifiers in exposure assessment and dose-response modeling, as descriptors of mode of action, and to characterize toxicity pathways. Vast amounts of genetic and epigenetic data may be generated by high-throughput technologies. These data can be useful for assessing variability and reducing uncertainty in extrapolations, and they may serve as the foundation upon which identification of biological perturbations would lead to a new paradigm of toxicity pathway-based risk assessments. PMID:26583908

Towards social acceptance of plant breeding by genome editing.

PubMed

Araki, Motoko; Ishii, Tetsuya

2015-03-01

Although genome-editing technologies facilitate efficient plant breeding without introducing a transgene, it is creating indistinct boundaries in the regulation of genetically modified organisms (GMOs). Rapid advances in plant breeding by genome-editing require the establishment of a new global policy for the new biotechnology, while filling the gap between process-based and product-based GMO regulations. In this Opinion article we review recent developments in producing major crops using genome-editing, and we propose a regulatory model that takes into account the various methodologies to achieve genetic modifications as well as the resulting types of mutation. Moreover, we discuss the future integration of genome-editing crops into society, specifically a possible response to the 'Right to Know' movement which demands labeling of food that contains genetically engineered ingredients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Infectious diseases: Surveillance, genetic modification and simulation

USGS Publications Warehouse

Koh, H. L.; Teh, S.Y.; De Angelis, D. L.; Jiang, J.

2011-01-01

Infectious diseases such as influenza and dengue have the potential of becoming a worldwide pandemic that may exert immense pressures on existing medical infrastructures. Careful surveillance of these diseases, supported by consistent model simulations, provides a means for tracking the disease evolution. The integrated surveillance and simulation program is essential in devising effective early warning systems and in implementing efficient emergency preparedness and control measures. This paper presents a summary of simulation analysis on influenza A (H1N1) 2009 in Malaysia. This simulation analysis provides insightful lessons regarding how disease surveillance and simulation should be performed in the future. This paper briefly discusses the controversy over the experimental field release of genetically modified (GM) Aedes aegypti mosquito in Malaysia. Model simulations indicate that the proposed release of GM mosquitoes is neither a viable nor a sustainable control strategy. ?? 2011 WIT Press.

Real-time quantitative polymerase chain reaction methods for four genetically modified maize varieties and maize DNA content in food.

PubMed

Brodmann, Peter D; Ilg, Evelyn C; Berthoud, Hélène; Herrmann, Andre

2002-01-01

Quantitative detection methods are needed for enforcement of the recently introduced labeling threshold for genetically modified organisms (GMOs) in food ingredients. This labeling threshold, which is set to 1% in the European Union and Switzerland, must be applied to all approved GMOs. Four different varieties of maize are approved in the European Union: the insect-resistant Bt176 maize (Maximizer), Btl 1 maize, Mon810 (YieldGard) maize, and the herbicide-tolerant T25 (Liberty Link) maize. Because the labeling must be considered individually for each ingredient, a quantitation system for the endogenous maize content is needed in addition to the GMO-specific detection systems. Quantitative real-time polymerase chain reaction detection methods were developed for the 4 approved genetically modified maize varieties and for an endogenous maize (invertase) gene system.

Efficient Generation of Gene-Modified Pigs Harboring Precise Orthologous Human Mutation via CRISPR/Cas9-Induced Homology-Directed Repair in Zygotes.

PubMed

Zhou, Xiaoyang; Wang, Lulu; Du, Yinan; Xie, Fei; Li, Liang; Liu, Yu; Liu, Chuanhong; Wang, Shiqiang; Zhang, Shibing; Huang, Xingxu; Wang, Yong; Wei, Hong

2016-01-01

Precise genetic mutation of model animals is highly valuable for functional investigation of human mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-induced homology-directed repair (HDR) is usually used for precise genetic mutation, being limited by the relatively low efficiency compared with that of non-homologous end joining (NHEJ). Although inhibition of NHEJ was shown to enhance HDR-derived mutation, in this work, without inhibition of NHEJ, we first generated gene-modified pigs harboring precise orthologous human mutation (Sox10 c.A325>T) via CRISPR/Cas9-induced HDR in zygotes using single-strand oligo DNA (ssODN) as template with an efficiency as high as 80%, indicating that pig zygotes exhibited high activities of HDR relative to NHEJ and were highly amendable to genetic mutation via CIRSPR/Cas9-induced HDR. Besides, we found a higher concentration of ssODN remarkably reduced HDR-derived mutation in pig zygotes, suggesting a possible balance for optimal HDR-derived mutation in zygotes between the excessive accessibility to HDR templates and the activities of HDR relative to NHEJ which appeared to be negatively correlated to ssODN concentration. In addition, the HDR-derived mutation, as well as those from NHEJ, extensively integrated into various tissues including gonad of founder pig without detected off-targeting, suggesting CRISPR/Cas9-induced HDR in zygotes is a reliable approach for precise genetic mutation in pigs. © 2015 WILEY PERIODICALS, INC.

Mutational screening in genes related with porto-pulmonary hypertension: An analysis of 6 cases.

PubMed

Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

2017-04-07

Portopulmonary hypertension (PPH) is a rare disease with a low incidence and without a clearly-identified genetic component. The aim of this work was to check genes and genetic modifiers related to pulmonary arterial hypertension in patients with PPH in order to clarify the molecular basis of the pathology. We selected a total of 6 patients with PPH and amplified the exonic regions and intronic flanking regions of the relevant genes and regions of interest of the genetic modifiers. Six patients diagnosed with PPH were analyzed and compared to 55 healthy individuals. Potentially-pathogenic mutations were identified in the analyzed genes of 5 patients. None of these mutations, which are highly conserved throughout evolution, were detected in the control patients nor different databases analyzed (1000 Genomes, ExAC and DECIPHER). After analyzing for genetic modifiers, we found different variations that could favor the onset of the disease. The genetic analysis carried out in this small cohort of patients with PPH revealed a large number of mutations, with the ENG gene showing the greatest mutational frequency. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

When gene medication is also genetic modification--regulating DNA treatment.

PubMed

Foss, Grethe S; Rogne, Sissel

2007-07-26

The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

Fast and sensitive in vivo studies under controlled environmental conditions to substitute long-term field trials with genetically modified plants.

PubMed

Horn, Patricia; Schlichting, André; Baum, Christel; Hammesfahr, Ute; Thiele-Bruhn, Sören; Leinweber, Peter; Broer, Inge

2017-02-10

We introduce an easy, fast and effective method to analyze the influence of genetically modified (GM) plants on soil and model organisms in the laboratory to substitute laborious and time consuming field trials. For the studies described here we focused on two GM plants of the so-called 3rd generation: GM plants producing pharmaceuticals (PMP) and plant made industrials (PMI). Cyanophycin synthetase (cphA) was chosen as model for PMI and Choleratoxin B (CTB) as model for PMP. The model genes are expressed in transgenic roots of composite Vicia hirsuta plants grown in petri dishes for semi-sterile growth or small containers filled with non-sterile soil. No significant influence of the model gene expression on root induction, growth, biomass, interaction with symbionts such as rhizobia (number, size and functionality of nodules, selection of nodulating strains) or arbuscular mycorrhizal fungi could be detected. In vitro, but not in situ under field conditions, structural diversity of the bulk soil microbial community between transgenic and non-transgenic cultivars was determined by PLFA pattern-derived ratios of bacteria: fungi and of gram + : gram - bacteria. Significant differences in PLFA ratios were associated with dissimilarities in the quantity and molecular composition of rhizodeposits as revealed by Py-FIMS analyses. Contrary to field trials, where small effects based on the transgene expression might be hidden by the immense influence of various environmental factors, our in vitro system can detect even minor effects and correlates them to transgene expression with less space, time and labour. Copyright © 2016 Elsevier B.V. All rights reserved.

Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

PubMed

Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

2016-04-01

Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes including, but not limited to, phosphorylation, cytoskeleton organization, axonal transport, regulation of cellular proteostasis, transcription, RNA metabolism, cell cycle regulation, and apoptosis. We discuss the utility and application of invertebrate models in elucidating the cellular and molecular functions of novel and uncharacterized disease modifiers identified in large-scale screens as well as for investigating the function of genes identified as risk factors in genome-wide association studies from human patients in the post-genomic era. In this review, we combined and summarized several large-scale modifier screens performed in invertebrate models to identify modifiers of tau toxicity. A summary of the screens show that diverse cellular processes are implicated in the modification of tau toxicity. Kinases and phosphatases are the most predominant class of modifiers followed by components required for cellular proteostasis and axonal transport and cytoskeleton elements. © 2016 International Society for Neurochemistry.

Genetic modifications for personal enhancement: a defence.

PubMed

Murphy, Timothy F

2014-04-01

Bioconservative commentators argue that parents should not take steps to modify the genetics of their children even in the name of enhancement because of the damage they predict for values, identities and relationships. Some commentators have even said that adults should not modify themselves through genetic interventions. One commentator worries that genetic modifications chosen by adults for themselves will undermine moral agency, lead to less valuable experiences and fracture people's sense of self. These worries are not justified, however, since the effects of modification will not undo moral agency as such. Adults can still have valuable experiences, even if some prior choices no longer seem meaningful. Changes at the genetic level will not always, either, alienate people from their own sense of self. On the contrary, genetic modifications can help amplify choice, enrich lives and consolidate identities. Ultimately, there is no moral requirement that people value their contingent genetic endowment to the exclusion of changes important to them in their future genetic identities. Through weighing risks and benefits, adults also have the power to consent to, and assume the risks of, genetic modifications for themselves in a way not possible in prenatal genetic interventions.

Unintended Effects in Genetically Modified Food/Feed Safety: A Way Forward.

PubMed

Fernandez, Antonio; Paoletti, Claudia

2018-04-20

Identifying and assessing unintended effects in genetically modified food and feed are considered paramount by the Food and Agricultural Organization (FAO), World Health Organization (WHO), and Codex Alimentarius, despite heated debate. This paper addresses outstanding needs: building consensus on the history-of-safe-use concept, harmonizing criteria to select appropriate conventional counterparts, and improving endpoint selection to identify unintended effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Over-expression of a putative oxidoreductase (UcpA) for increasing furfural or 5-hydroxymethylfurfural tolerance

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

Wang, Xuan; Miller, Elliot N.; Yomano, Lorraine P.

The subject invention pertains to overexpression of a putative oxidoreductase (ucpA) for increasing furfural tolerance in genetically modified microorganisms. Genetically modified microorganisms capable of overexpressing UcpA are also provided. Increased expression of ucpA was shown to increase furfural tolerance by 50%, and to permit the fermentation of sugars to products in the presence of 15 mM furfural.

Growth promotion of genetically modified hematopoietic progenitors using an antibody/c-Mpl chimera.

PubMed

Kawahara, Masahiro; Chen, Jianhong; Sogo, Takahiro; Teng, Jinying; Otsu, Makoto; Onodera, Masafumi; Nakauchi, Hiromitsu; Ueda, Hiroshi; Nagamune, Teruyuki

2011-09-01

Thrombopoietin is a potent cytokine that exerts proliferation of hematopoietic stem cells (HSCs) through its cognate receptor, c-Mpl. Therefore, mimicry of c-Mpl signaling by a receptor recognizing an artificial ligand would be attractive to attain specific expansion of genetically modified HSCs. Here we propose a system enabling selective expansion of genetically modified cells using an antibody/receptor chimera that can be activated by a specific antigen. We constructed an antibody/c-Mpl chimera, in which single-chain Fv (ScFv) of an anti-fluorescein antibody was tethered to the extracellular D2 domain of the erythropoietin receptor and transmembrane/cytoplasmic domains of c-Mpl. When the chimera was expressed in interleukin (IL)-3-dependent pro-B cell line Ba/F3, genetically modified cells were selectively expanded in the presence of fluorescein-conjugated BSA (BSA-FL) as a specific antigen. Furthermore, highly purified mouse HSCs transduced with the retrovirus carrying antibody/c-Mpl chimera gene proliferated in vitro in response to BSA-FL, and the cells retained in vivo long-term repopulating abilities. These results demonstrate that the antibody/c-Mpl chimera is capable of signal transduction that mimics wild-type c-Mpl signaling. Copyright © 2011 Elsevier Ltd. All rights reserved.

Simultaneous Detection of Genetically Modified Organisms in a Mixture by Multiplex PCR-Chip Capillary Electrophoresis.

PubMed

Patwardhan, Supriya; Dasari, Srikanth; Bhagavatula, Krishna; Mueller, Steffen; Deepak, Saligrama Adavigowda; Ghosh, Sudip; Basak, Sanjay

2015-01-01

An efficient PCR-based method to trace genetically modified food and feed products is in demand due to regulatory requirements and contaminant issues in India. However, post-PCR detection with conventional methods has limited sensitivity in amplicon separation that is crucial in multiplexing. The study aimed to develop a sensitive post-PCR detection method by using PCR-chip capillary electrophoresis (PCR-CCE) to detect and identify specific genetically modified organisms in their genomic DNA mixture by targeting event-specific nucleotide sequences. Using the PCR-CCE approach, novel multiplex methods were developed to detect MON531 cotton, EH 92-527-1 potato, Bt176 maize, GT73 canola, or GA21 maize simultaneously when their genomic DNAs in mixtures were amplified using their primer mixture. The repeatability RSD (RSDr) of the peak migration time was 0.06 and 3.88% for the MON531 and Bt176, respectively. The RSD (RSDR) of the Cry1Ac peak ranged from 0.12 to 0.40% in multiplex methods. The method was sensitive in resolving amplicon of size difference up to 4 bp. The PCR-CCE method is suitable to detect multiple genetically modified events in a composite DNA sample by tagging their event specific sequences.

Genetically modified T cells in cancer therapy: opportunities and challenges

PubMed Central

Sharpe, Michaela; Mount, Natalie

2015-01-01

Tumours use many strategies to evade the host immune response, including downregulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumour environment. T cells play a key role in cell-mediated immunity and, recently, strategies to genetically modify T cells either through altering the specificity of the T cell receptor (TCR) or through introducing antibody-like recognition in chimeric antigen receptors (CARs) have made substantial advances. The potential of these approaches has been demonstrated in particular by the successful use of genetically modified T cells to treat B cell haematological malignancies in clinical trials. This clinical success is reflected in the growing number of strategic partnerships in this area that have attracted a high level of investment and involve large pharmaceutical organisations. Although our understanding of the factors that influence the safety and efficacy of these therapies has increased, challenges for bringing genetically modified T-cell immunotherapy to many patients with different tumour types remain. These challenges range from the selection of antigen targets and dealing with regulatory and safety issues to successfully navigating the routes to commercial development. However, the encouraging clinical data, the progress in the scientific understanding of tumour immunology and the improvements in the manufacture of cell products are all advancing the clinical translation of these important cellular immunotherapies. PMID:26035842

Learning Strategy Selection in the Water Maze and Hippocampal CREB Phosphorylation Differ in Two Inbred Strains of Mice

ERIC Educational Resources Information Center

Sung, Jin-Young; Goo, June-Seo; Lee, Dong-Eun; Jin, Da-Qing; Bizon, Jennifer L.; Gallagher, Michela; Han, Jung-Soo

2008-01-01

Learning strategy selection was assessed in two different inbred strains of mice, C57BL/6 and DBA/2, which are used for developing genetically modified mouse models. Male mice received a training protocol in a water maze using alternating blocks of visible and hidden platform trials, during which mice escaped to a single location. After training,…

Development of a Novel Treatment for Food Allergy Using a New Genetically Defined Mouse Model of the Disease

DTIC Science & Technology

2012-07-01

peanut allergy, and whether treatment with losartan , an angiotensin II (ATII) receptor blocker that inhibits TGFbeta signaling, reduces the development...increased effector responses, or both. We will also examine how treatment with losartan modifies the allergic phenotype in LDS mice. 15...SUBJECT TERMS Loeys Dietz Syndrome, food allergy, eosinophilic esophagitis, anaphylaxis, TGFbeta, losartan 16. SECURITY CLASSIFICATION OF: 17

Irradiation influence on the detection of genetic-modified soybeans

NASA Astrophysics Data System (ADS)

Villavicencio, A. L. C. H.; Araújo, M. M.; Baldasso, J. G.; Aquino, S.; Konietzny, U.; Greiner, R.

2004-09-01

Three soybean varieties were analyzed to evaluate the irradiation influence on the detection of genetic modification. Samples were treated in a 60Co facility at dose levels of 0, 500, 800, and 1000Gy. The seeds were at first analyzed by Comet Assay as a rapid screening irradiation detection method. Secondly, germination test was performed to detect the viability of irradiated soybeans. Finally, because of its high sensitivity, its specificity and rapidity the polimerase chain reaction was the method applied for genetic modified organism detection. The analysis of DNA by the single technique of microgel electrophoresis of single cells (DNA Comet Assay) showed that DNA damage increased with increasing radiation doses. No negative influence of irradiation on the genetic modification detection was found.

Application of Zebrafish Model to Environmental Toxicology.

PubMed

Komoike, Yuta; Matsuoka, Masato

2016-01-01

Recently, a tropical freshwater fish, the zebrafish, has been generally used as a useful model organism in various fields of life science worldwide. The zebrafish model has also been applied to environmental toxicology; however, in Japan, it has not yet become widely used. In this review, we will introduce the biological and historical backgrounds of zebrafish as an animal model and their breeding. We then present the current status of toxicological experiments using zebrafish that were treated with some important environmental contaminants, including cadmium, organic mercury, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and tributyltin. Finally, the future possible application of genetically modified zebrafish to the study of environmental toxicology is discussed.

The association of the blood lead level and serum lipid concentrations may be modified by the genetic combination of the metallothionein 2A polymorphisms rs10636 GC and rs28366003 AA.

PubMed

Yang, Chen-Cheng; Chuang, Chih-Shien; Lin, Chia-I; Wang, Chao-Ling; Huang, Yung-Cheng; Chuang, Hung-Yi

Lead in blood can stimulate lipid oxidation in phosphatidylcholine and increase peroxidation in lipids. Metallothionein (MT) is a cysteine-rich protein that can influence the detoxification of heavy metals and scavenge oxidative stress for free radicals. One of the most expressive functional genes in humans is the MT2A gene. This study aims to determine if the association of the blood lead level and lipid biomarkers was influenced by MT2A polymorphisms. We recruited 677 participants after informed consent was obtained. All the samples collected were analyzed for lipid biomarkers and blood lead levels and were genotyped for MT2A polymorphisms by reverse transcription polymerase chain reaction. A short questionnaire collected the medical history and alcohol and cigarette consumption information. The data were used for descriptive analyses and linear regression models. The investigation revealed that lead elevated concentration increased low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol (HDL-C) by multiple linear models. The carriers of the rs10636 GC-rs28366003 AA genetic combination may be less susceptive to lead elevated concentration on HDL-C than other types. In conclusion, the association of the blood lead level and HDL-C may be modified by the MT2A genetic combination: the rs10636 GC-rs28366003 AA genotype could play a protective role in lead elevated concentration on HDL-C in humans. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study.

PubMed

Akinkugbe, A A; Avery, C L; Barritt, A S; Cole, S R; Lerch, M; Mayerle, J; Offenbacher, S; Petersmann, A; Nauck, M; Völzke, H; Slade, G D; Heiss, G; Kocher, T; Holtfreter, B

2017-11-01

An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, <30%, ≥30%) with probing pocket depth (PD) ≥4 mm, and NAFLD status was determined using liver ultrasound assessment. Serum CRP levels were assayed at a central laboratory, and single-nucleotide polymorphisms previously identified through genome-wide association studies as robustly associated with serum CRP were combined into a weighted genetic CRP score (wGS CRP ). Logistic regression models estimated the association between periodontitis and NAFLD within strata of serum CRP and separately within strata of the wGS CRP . The prevalence of NAFLD was 26.4% (95% confidence interval [CI], 24.6, 28.1) while 17.8% (95% CI, 16.0-19.6) had ≥30% of sites with PD ≥4 mm. Whereas the wGS CRP was not a modifier ( P interaction = 0.8) on the multiplicative scale, serum CRP modified the relationship between periodontitis and NAFLD ( P interaction = 0.01). The covariate-adjusted prevalence odds ratio of NAFLD comparing participants with ≥30% of sites with PD ≥4 mm to those with no site affected was 2.39 (95% CI, 1.32-4.31) among participants with serum CRP <1 mg/L. The corresponding estimate was 0.97 (95% CI, 0.57-1.66) for participants with serum CRP levels of 1 to 3 mg/L and 1.12 (95% CI, 0.65-1.93) for participants with serum CRP >3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

PubMed Central

Zhen, Hanson H.; Oro, Anthony E.

2013-01-01

Hair follicle morphogenesis, a complex process requiring interaction between epithelia-derived keratinocytes and the underlying mesenchyme, is an attractive model system to study organ development and tissue-specific signaling. Although hair follicle development is genetically tractable, fast and reproducible analysis of factors essential for this process remains a challenge. Here we describe a procedure to generate targeted overexpression or shRNA-mediated knockdown of factors using lentivirus in a tissue-specific manner. Using a modified version of a hair regeneration model 5, 6, 11, we can achieve robust gain- or loss-of-function analysis in primary mouse keratinocytes or dermal cells to facilitate study of epithelial-mesenchymal signaling pathways that lead to hair follicle morphogenesis. We describe how to isolate fresh primary mouse keratinocytes and dermal cells, which contain dermal papilla cells and their precursors, deliver lentivirus containing either shRNA or cDNA to one of the cell populations, and combine the cells to generate fully formed hair follicles on the backs of nude mice. This approach allows analysis of tissue-specific factors required to generate hair follicles within three weeks and provides a fast and convenient companion to existing genetic models. PMID:23486463

An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis.

PubMed

Jin, Huifeng; Cheng, Haojie; Chen, Wei; Sheng, Xiaoming; Levy, Mark A; Brown, Mark J; Tian, Junqiang

2018-05-01

The single nucleotide polymorphism of the gene 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. We hypothesized that variability in this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers, confounders, or both, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates. We systematically extracted from published studies the data on tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting metadata set was first used to analyze the covariates' modifying effect by meta-regression and other statistical means. Subsequently, we controlled for this modifying effect by genotype-stratifying tHcy data and analyzed the variability in the risk resulting from the confounding of covariates. The data set contains data on 36 rs1801133 covariates that were collected from 114,799 participants and 256 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification as well as confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner. We showed an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public, who increasingly receive genetic data from commercial services without interpretation of its clinical relevance. This study was registered at Research Registry with the registration number reviewregistry328.

Gene–arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

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

Farzan, Shohreh F.; Department of Population Health, New York University School of Medicine, New York, NY; Karagas, Margaret R.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7 years of follow-upmore » in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction = 0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23 mm Hg (95% CI: 1.14–3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13 mm Hg (95% CI: 0.02–0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time. - Highlights: • Arsenic (As) exposure has been associated with blood pressure increases over time. • Genetic polymorphisms may modify the association between As and blood pressure. • An interaction between CYBA rs3794624 and well As increased annual pulse pressure. • Genetic variants may contribute to As-related blood pressure increases over time.« less

DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases.

PubMed

Bettencourt, Conceição; Hensman-Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas-Gómez, Petra; García-Velázquez, Lizbeth Esmeralda; Alonso-Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J; Jones, Lesley

2016-06-01

The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome-wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single-nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10(-5) ). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10(-5) ) and all SCAs (p = 2.22 × 10(-4) ) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10(-5) ), all in the same direction as in the HD GWAS. We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983-990. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Humanized mouse models: Application to human diseases.

PubMed

Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Genome engineering in cattle: recent technological advancements.

PubMed

Wang, Zhongde

2015-02-01

Great strides in technological advancements have been made in the past decade in cattle genome engineering. First, the success of cloning cattle by somatic cell nuclear transfer (SCNT) or chromatin transfer (CT) is a significant advancement that has made obsolete the need for using embryonic stem (ES) cells to conduct cell-mediated genome engineering, whereby site-specific genetic modifications can be conducted in bovine somatic cells via DNA homologous recombination (HR) and whereby genetically engineered cattle can subsequently be produced by animal cloning from the genetically modified cells. With this approach, a chosen bovine genomic locus can be precisely modified in somatic cells, such as to knock out (KO) or knock in (KI) a gene via HR, a gene-targeting strategy that had almost exclusively been used in mouse ES cells. Furthermore, by the creative application of embryonic cloning to rejuvenate somatic cells, cattle genome can be sequentially modified in the same line of somatic cells and complex genetic modifications have been achieved in cattle. Very recently, the development of designer nucleases-such as zinc finger nucleases (ZFNs) and transcription activator-like effector nuclease (TALENs), and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-has enabled highly efficient and more facile genome engineering in cattle. Most notably, by employing such designer nucleases, genomes can be engineered at single-nucleotide precision; this process is now often referred to as genome or gene editing. The above achievements are a drastic departure from the traditional methods of creating genetically modified cattle, where foreign DNAs are randomly integrated into the animal genome, most often along with the integrations of bacterial or viral DNAs. Here, I review the most recent technological developments in cattle genome engineering by highlighting some of the major achievements in creating genetically engineered cattle for agricultural and biomedical applications.

Experimental Performance of a Genetic Algorithm for Airborne Strategic Conflict Resolution

NASA Technical Reports Server (NTRS)

Karr, David A.; Vivona, Robert A.; Roscoe, David A.; DePascale, Stephen M.; Consiglio, Maria

2009-01-01

The Autonomous Operations Planner, a research prototype flight-deck decision support tool to enable airborne self-separation, uses a pattern-based genetic algorithm to resolve predicted conflicts between the ownship and traffic aircraft. Conflicts are resolved by modifying the active route within the ownship s flight management system according to a predefined set of maneuver pattern templates. The performance of this pattern-based genetic algorithm was evaluated in the context of batch-mode Monte Carlo simulations running over 3600 flight hours of autonomous aircraft in en-route airspace under conditions ranging from typical current traffic densities to several times that level. Encountering over 8900 conflicts during two simulation experiments, the genetic algorithm was able to resolve all but three conflicts, while maintaining a required time of arrival constraint for most aircraft. Actual elapsed running time for the algorithm was consistent with conflict resolution in real time. The paper presents details of the genetic algorithm s design, along with mathematical models of the algorithm s performance and observations regarding the effectiveness of using complimentary maneuver patterns when multiple resolutions by the same aircraft were required.

Experimental Performance of a Genetic Algorithm for Airborne Strategic Conflict Resolution

NASA Technical Reports Server (NTRS)

Karr, David A.; Vivona, Robert A.; Roscoe, David A.; DePascale, Stephen M.; Consiglio, Maria

2009-01-01

The Autonomous Operations Planner, a research prototype flight-deck decision support tool to enable airborne self-separation, uses a pattern-based genetic algorithm to resolve predicted conflicts between the ownship and traffic aircraft. Conflicts are resolved by modifying the active route within the ownship's flight management system according to a predefined set of maneuver pattern templates. The performance of this pattern-based genetic algorithm was evaluated in the context of batch-mode Monte Carlo simulations running over 3600 flight hours of autonomous aircraft in en-route airspace under conditions ranging from typical current traffic densities to several times that level. Encountering over 8900 conflicts during two simulation experiments, the genetic algorithm was able to resolve all but three conflicts, while maintaining a required time of arrival constraint for most aircraft. Actual elapsed running time for the algorithm was consistent with conflict resolution in real time. The paper presents details of the genetic algorithm's design, along with mathematical models of the algorithm's performance and observations regarding the effectiveness of using complimentary maneuver patterns when multiple resolutions by the same aircraft were required.

Site-Specific Genome Engineering in Human Pluripotent Stem Cells.

PubMed

Merkert, Sylvia; Martin, Ulrich

2016-06-24

The possibility to generate patient-specific induced pluripotent stem cells (iPSCs) offers an unprecedented potential of applications in clinical therapy and medical research. Human iPSCs and their differentiated derivatives are tools for diseases modelling, drug discovery, safety pharmacology, and toxicology. Moreover, they allow for the engineering of bioartificial tissue and are promising candidates for cellular therapies. For many of these applications, the ability to genetically modify pluripotent stem cells (PSCs) is indispensable, but efficient site-specific and safe technologies for genetic engineering of PSCs were developed only recently. By now, customized engineered nucleases provide excellent tools for targeted genome editing, opening new perspectives for biomedical research and cellular therapies.

'Knock, and it shall be opened': knocking out and knocking in to reveal mechanisms of disease and novel therapies.

PubMed

Hacking, Douglas F

2008-12-01

Recent significant advances in molecular biology have generated genetically modified bacteria, yeast, nematodes, fruit flies, and fish. However, it is the genetic modification of mammalian model organisms, particularly the mouse, that has the greatest potential to shed light on human development, physiology and pathology in ways that have significant implications for neonatal and paediatric clinical practice. Here, we review some of the techniques for knocking out (inactivating), mutating and knocking in (inserting) selected genes that are important to neonatology and show how this research will lead both to a better understanding of disease and to novel therapies for infants and children.

Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

PubMed Central

Kinnunen, Tarja K.

2014-01-01

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease. PMID:25054285

A PDX/organoid biobank of advanced prostate cancers captures genomic and phenotypic heterogeneity for disease modeling and therapeutic screening.

PubMed

Beshiri, Michael L; Tice, Caitlin M; Tran, Crystal; Nguyen, Holly M; Sowalsky, Adam G; Agarwal, Supreet; Jansson, Keith H; Yang, Qi; McGowen, Kerry A; Yin, Juan Juan; Alilin, Aian Neil; Karzai, Fatima H; Dahut, William; Corey, Eva; Kelly, Kathleen

2018-05-10

Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis. Using 20 models from the LuCaP mCRPC PDX cohort, including adenocarcinoma and neuroendocrine lineages, we systematically tested > 20 modifications to prostate organoid conditions. Organoids were evaluated for genomic and phenotypic stability and continued reliance on the AR signaling pathway. The utility of the platform as a genotype-dependent model of drug sensitivity was tested with olaparib and carboplatin. All PDX models proliferated as organoids in culture. Greater than fifty percent could be continuously cultured long-term in modified conditions; however, none of the PDXs could be established long-term as organoids under previously-reported conditions. Additionally, the modified conditions improved the establishment of patient biopsies over current methods. The genomic heterogeneity of the PDXs, was conserved in organoids. Lineage markers and transcriptomes were maintained between PDXs and organoids. Dependence on AR signaling, was preserved in adenocarcinoma organoids, replicating a dominant characteristic of CRPC. Finally, we observed maximum cytotoxicity to the PARP inhibitor olaparib in BRCA2 -/- organoids, similar to responses observed in patients. The LuCaP PDX/organoid models provide an expansive, genetically-characterized platform to investigate mechanisms of pathogenesis as well as therapeutic responses and their molecular correlates in mCRPC. Copyright ©2018, American Association for Cancer Research.

Improve T Cell Therapy in Neuroblastoma

DTIC Science & Technology

2012-07-01

Epstein - Barr - virus (EBV)-specific cytotoxic T lymphocytes (EBV-CTLs) genetically modified to express a chimeric antigen receptor (CAR-GD2) targeting the...A. Krance, M. K. Brenner, and C. M. Rooney. 1996. Long-term restoration of immunity against Epstein - Barr virus infection by adoptive transfer of gene... Barr - virus (EBV)- specific cytotoxic T l ymphocytes (EBV-CTLs) genetically modified to express a c himeric antigen receptor (CAR-GD2) targeting the GD2

Host cells and methods for producing isoprenyl alkanoates

DOEpatents

Lee, Taek Soon; Fortman, Jeffrey L.; Keasling, Jay D.

2015-12-01

The invention provides for a method of producing an isoprenyl alkanoate in a genetically modified host cell. In one embodiment, the method comprises culturing a genetically modified host cell which expresses an enzyme capable of catalyzing the esterification of an isoprenol and a straight-chain fatty acid, such as an alcohol acetyltransferase (AAT), wax ester synthase/diacylglycerol acyltransferase (WS/DGAT) or lipase, under a suitable condition so that the isoprenyl alkanoate is produced.

The use of genetically modified Saccharomyces cerevisiae strains in the wine industry.

PubMed

Schuller, Dorit; Casal, Margarida

2005-08-01

In recent decades, science and food technology have contributed at an accelerated rate to the introduction of new products to satisfy nutritional, socio-economic and quality requirements. With the emergence of modern molecular genetics, the industrial importance of Saccharomyces cerevisiae, is continuously extended. The demand for suitable genetically modified (GM) S. cerevisiae strains for the biofuel, bakery and beverage industries or for the production of biotechnological products (e.g. enzymes, pharmaceutical products) will continuously grow in the future. Numerous specialised S. cerevisiae wine strains were obtained in recent years, possessing a wide range of optimised or novel oenological properties, capable of satisfying the demanding nature of modern winemaking practise. The unlocking of transcriptome, proteome and metabolome complexities will contribute decisively to the knowledge about the genetic make-up of commercial yeast strains and will influence wine strain improvement via genetic engineering. The most relevant advances regarding the importance and implications of the use of GM yeast strains in the wine industry are discussed in this mini-review. In this work, various aspects are considered including the strategies used for the construction of strains with respect to current legislation requirements, the environmental risk evaluations concerning the deliberate release of genetically modified yeast strains, the methods for detection of recombinant DNA and protein that are currently under evaluation, and the reasons behind the critical public perception towards the application of such strains.

Harnessing biodiesel-producing microbes: from genetic engineering of lipase to metabolic engineering of fatty acid biosynthetic pathway.

PubMed

Yan, Jinyong; Yan, Yunjun; Madzak, Catherine; Han, Bingnan

2017-02-01

Microbial production routes, notably whole-cell lipase-mediated biotransformation and fatty-acids-derived biosynthesis, offer new opportunities for synthesizing biodiesel. They compare favorably to immobilized lipase and chemically catalyzed processes. Genetically modified whole-cell lipase-mediated in vitro route, together with in vivo and ex vivo microbial biosynthesis routes, constitutes emerging and rapidly developing research areas for effective production of biodiesel. This review presents recent advances in customizing microorganisms for producing biodiesel, via genetic engineering of lipases and metabolic engineering (including system regulation) of fatty-acids-derived pathways. Microbial hosts used include Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and Aspergillus oryzae. These microbial cells can be genetically modified to produce lipases under different forms: intracellularly expressed, secreted or surface-displayed. They can be metabolically redesigned and systematically regulated to obtain balanced biodiesel-producing cells, as highlighted in this study. Such genetically or metabolically modified microbial cells can support not only in vitro biotransformation of various common oil feedstocks to biodiesel, but also de novo biosynthesis of biodiesel from glucose, glycerol or even cellulosic biomass. We believe that the genetically tractable oleaginous yeast Yarrowia lipolytica could be developed to an effective biodiesel-producing microbial cell factory. For this purpose, we propose several engineered pathways, based on lipase and wax ester synthase, in this promising oleaginous host.

A strategy for genetic modification of the spike-encoding segment of human reovirus T3D for reovirus targeting.

PubMed

van den Wollenberg, D J M; van den Hengel, S K; Dautzenberg, I J C; Cramer, S J; Kranenburg, O; Hoeben, R C

2008-12-01

Human Orthoreovirus Type 3 Dearing is not pathogenic to humans and has been evaluated clinically as an oncolytic agent. Its transduction efficiency and the tumor cell selectivity may be enhanced by incorporating ligands for alternative receptors. However, the genetic modification of reoviruses has been difficult, and genetic targeting of reoviruses has not been reported so far. Here we describe a technique for generating genetically targeted reoviruses. The propagation of wild-type reoviruses on cells expressing a modified sigma 1-encoding segment embedded in a conventional RNA polymerase II transcript leads to substitution of the wild-type genome segment by the modified version. This technique was used for generating reoviruses that are genetically targeted to an artificial receptor expressed on U118MG cells. These cells lack the junction adhesion molecule-1 and therefore resist infection by wild-type reoviruses. The targeted reoviruses were engineered to carry the ligand for this receptor at the C terminus of the sigma 1 spike protein. This demonstrates that the C terminus of the sigma 1 protein is a suitable locale for the insertion of oligopeptide ligands and that targeting of reoviruses is feasible. The genetically targeted viruses can be propagated using the modified U118MG cells as helper cells. This technique may be applicable for the improvement of human reoviruses as oncolytic agents.

Genetically modified food in perspective: an inquiry-based curriculum to help middle school students make sense of tradeoffs

NASA Astrophysics Data System (ADS)

Seethaler, Sherry; Linn, Marcia

To understand how students learn about science controversy, this study examines students' reasoning about tradeoffs in the context of a technology-enhanced curriculum about genetically modified food. The curriculum was designed and refined based on the Scaffolded Knowledge Integration Framework to help students sort and integrate their initial ideas and those presented in the curriculum. Pre-test and post-test scores from 190 students show that students made significant (p < 0.0001) gains in their understanding of the genetically modified food controversy. Analyses of students' final papers, in which they took and defended a position on what type of agricultural practice should be used in their geographical region, showed that students were able to provide evidence both for and against their positions, but were less explicit about how they weighed these tradeoffs. These results provide important insights into students' thinking and have implications for curricular design.

Identification and quantification of genetically modified Moonshade carnation lines using conventional and TaqMan real-time polymerase chain reaction methods.

PubMed

Li, Peng; Jia, Junwei; Bai, Lan; Pan, Aihu; Tang, Xueming

2013-07-01

Genetically modified carnation (Dianthus caryophyllus L.) Moonshade was approved for planting and commercialization in several countries from 2004. Developing methods for analyzing Moonshade is necessary for implementing genetically modified organism labeling regulations. In this study, the 5'-transgene integration sequence was isolated using thermal asymmetric interlaced (TAIL)-PCR. Based upon the 5'-transgene integration sequence, conventional and TaqMan real-time PCR assays were established. The relative limit of detection for the conventional PCR assay was 0.05 % for Moonshade using 100 ng total carnation genomic DNA, corresponding to approximately 79 copies of the carnation haploid genome, and the limits of detection and quantification of the TaqMan real-time PCR assay were estimated to be 51 and 254 copies of haploid carnation genomic DNA, respectively. These results are useful for identifying and quantifying Moonshade and its derivatives.

Development and Evaluation of Event-Specific Quantitative PCR Method for Genetically Modified Soybean MON87701.

PubMed

Tsukahara, Keita; Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Nishimaki-Mogami, Tomoko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

2016-01-01

A real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) soybean event, MON87701. First, a standard plasmid for MON87701 quantification was constructed. The conversion factor (C f ) required to calculate the amount of genetically modified organism (GMO) was experimentally determined for a real-time PCR instrument. The determined C f for the real-time PCR instrument was 1.24. For the evaluation of the developed method, a blind test was carried out in an inter-laboratory trial. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr), respectively. The determined biases and the RSDr values were less than 30 and 13%, respectively, at all evaluated concentrations. The limit of quantitation of the method was 0.5%, and the developed method would thus be applicable for practical analyses for the detection and quantification of MON87701.

Loop-mediated isothermal amplification (LAMP) method for detection of genetically modified maize T25.

PubMed

Xu, Junyi; Zheng, Qiuyue; Yu, Ling; Liu, Ran; Zhao, Xin; Wang, Gang; Wang, Qinghua; Cao, Jijuan

2013-11-01

The loop-mediated isothermal amplification (LAMP) assay indicates a potential and valuable means for genetically modified organism (GMO) detection especially for its rapidity, simplicity, and low cost. We developed and evaluated the specificity and sensitivity of the LAMP method for rapid detection of the genetically modified (GM) maize T25. A set of six specific primers was successfully designed to recognize six distinct sequences on the target gene, including a pair of inner primers, a pair of outer primers, and a pair of loop primers. The optimum reaction temperature and time were verified to be 65°C and 45 min, respectively. The detection limit of this LAMP assay was 5 g kg(-1) GMO component. Comparative experiments showed that the LAMP assay was a simple, rapid, accurate, and specific method for detecting the GM maize T25.

Development and interlaboratory validation of quantitative polymerase chain reaction method for screening analysis of genetically modified soybeans.

PubMed

Takabatake, Reona; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

2013-01-01

A novel real-time polymerase chain reaction (PCR)-based quantitative screening method was developed for three genetically modified soybeans: RRS, A2704-12, and MON89788. The 35S promoter (P35S) of cauliflower mosaic virus is introduced into RRS and A2704-12 but not MON89788. We then designed a screening method comprised of the combination of the quantification of P35S and the event-specific quantification of MON89788. The conversion factor (Cf) required to convert the amount of a genetically modified organism (GMO) from a copy number ratio to a weight ratio was determined experimentally. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDR), respectively. The determined RSDR values for the method were less than 25% for both targets. We consider that the developed method would be suitable for the simple detection and approximate quantification of GMO.

Listened to, but not heard! The failure to represent the public in genetically modified food policies.

PubMed

Lassen, Jesper

2018-04-01

'In the mid-1990s, a mismatch was addressed between European genetically modified food policy, which focused primarily on risks and economic prospects, and public anxieties, which also included other concerns, and there was a development in European food policy toward the inclusion of what were referred to as "ethical aspects." Using parliamentary debates in Denmark in 2002 and 2015 as a case, this article examines how three storylines of concern that were visible in public discourse at the time were represented by the decision makers in parliament. It shows that core public concerns raising fundamental questions about genetically modified foods, and in particular their perceived unnaturalness, were not considered in the parliamentary debates. It is suggested that the failure of the parliament to represent the public may undermine the legitimacy of politicians and lead to disillusionment with parliamentary government.

Regulatory science requirements of labeling of genetically modified food.

PubMed

Moghissi, A Alan; Jaeger, Lisa M; Shafei, Dania; Bloom, Lindsey L

2018-05-01

This paper provides an overview of the evolution of food labeling in the USA. It briefly describes the three phases of agricultural development consisting of naturally occurring, cross-bred, and genetically engineered, edited or modified crops, otherwise known as Genetically Modified Organisms (GMO). It uses the Best Available Regulatory Science (BARS) and Metrics for Evaluation of Regulatory Science Claims (MERSC) to evaluate the scientific validity of claims applicable to GMO and the Best Available Public Information (BAPI) to evaluate the pronouncements by public media and others. Subsequently claims on health risk, ecological risk, consumer choice, and corporate greed are evaluated based on BARS/MERSC and BAPI. The paper concludes by suggesting that labeling of food containing GMO should consider the consumer's choice, such as the food used by those who desire kosher and halal food. Furthermore, the consumer choice is already met by the exclusion of GMO in organic food.

Dynamics of list-server discussion on genetically modified foods.

PubMed

Triunfol, Marcia L; Hines, Pamela J

2004-04-01

Computer-mediated discussion lists, or list-servers, are popular tools in settings ranging from professional to personal to educational. A discussion list on genetically modified food (GMF) was created in September 2000 as part of the Forum on Genetically Modified Food developed by Science Controversies: Online Partnerships in Education (SCOPE), an educational project that uses computer resources to aid research and learning around unresolved scientific questions. The discussion list "GMF-Science" was actively supported from January 2001 to May 2002. The GMF-Science list welcomed anyone interested in discussing the controversies surrounding GMF. Here, we analyze the dynamics of the discussions and how the GMF-Science list may contribute to learning. Activity on the GMF-Science discussion list reflected some but not all the controversies that were appearing in more traditional publication formats, broached other topics not well represented in the published literature, and tended to leave undiscussed the more technical research developments.

Loop-mediated isothermal amplification (LAMP) method for detection of genetically modified maize T25

PubMed Central

Xu, Junyi; Zheng, Qiuyue; Yu, Ling; Liu, Ran; Zhao, Xin; Wang, Gang; Wang, Qinghua; Cao, Jijuan

2013-01-01

The loop-mediated isothermal amplification (LAMP) assay indicates a potential and valuable means for genetically modified organism (GMO) detection especially for its rapidity, simplicity, and low cost. We developed and evaluated the specificity and sensitivity of the LAMP method for rapid detection of the genetically modified (GM) maize T25. A set of six specific primers was successfully designed to recognize six distinct sequences on the target gene, including a pair of inner primers, a pair of outer primers, and a pair of loop primers. The optimum reaction temperature and time were verified to be 65°C and 45 min, respectively. The detection limit of this LAMP assay was 5 g kg−1 GMO component. Comparative experiments showed that the LAMP assay was a simple, rapid, accurate, and specific method for detecting the GM maize T25. PMID:24804053

[The EU law on genetically modified organisms: the European Commission changes the strategy in order to allow, restrict, or prohibit its culture].

PubMed

González Vaqué, Luis

2010-01-01

On July 13 2010, the European Commission adopted a series of measures which outline a new approach on Genetically Modified Organisms (GMOs) cultivation in the Member States. This proposal, which still retains the basis of the existing science-based GMO authorisation system, will be implemented through: a Communication from the Commission, explaining the new approach on the freedom for Member States to decide on the cultivation of genetically modified crops; the "Proposal for a Regulation of the European Parliament and of the Council amending Directive 2001/18/EC as regards the possibility for the Member States to restrict or prohibit the cultivation of GMOs in their territory"; and a new "European Commission Recommendation (2010/C 200/01) of 13 July 2010 on guidelines for the development of national co-existence measures to avoid the unintended presence of GMOs in conventional and organic crops".

[Supervision of foods containing components of genetically modified organisms and the problems of labeling this type of products].

PubMed

Onishchenko, G G

2010-01-01

Commercial production of genetically modified (GM) crops as food or feed is regarded as a promising social area in the development of modern biotechnology. The Russian Federation has set up a governmental system to regulate the use of biotechnology products, which is based on Russian and foreign experience and the most up-to-date scientific approaches. The system for evaluating the quality and safety of GM foodstuffs envisages the postregistration monitoring of their circulation as an obligatory stage. For these purposes, the world community applies two methods: enzyme immunoassay and polymerase chain reaction. It should be noted that there are various approaches to GM food labeling in the world; this raises the question of whether the labeling of foods that are prepared from genetically modified organisms, but contain no protein or DNA is to be introduced in Russia, as in the European Union.

Discrimination of genetically modified sugar beets based on terahertz spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Tao; Li, Zhi; Yin, Xianhua; Hu, Fangrong; Hu, Cong

2016-01-01

The objective of this paper was to apply terahertz (THz) spectroscopy combined with chemometrics techniques for discrimination of genetically modified (GM) and non-GM sugar beets. In this paper, the THz spectra of 84 sugar beet samples (36 GM sugar beets and 48 non-GM ones) were obtained by using terahertz time-domain spectroscopy (THz-TDS) system in the frequency range from 0.2 to 1.2 THz. Three chemometrics methods, principal component analysis (PCA), discriminant analysis (DA) and discriminant partial least squares (DPLS), were employed to classify sugar beet samples into two groups: genetically modified organisms (GMOs) and non-GMOs. The DPLS method yielded the best classification result, and the percentages of successful classification for GM and non-GM sugar beets were both 100%. Results of the present study demonstrate the usefulness of THz spectroscopy together with chemometrics methods as a powerful tool to distinguish GM and non-GM sugar beets.

Hypothetical link between infertility and genetically modified food.

PubMed

Gao, Mingxia; Li, Bin; Yuan, Wenzhen; Zhao, Lihui; Zhang, Xuehong

2014-01-01

It is speculated that genetically modified food (GMF)/genetically modified organism (GMO) is responsible for infertility development. The risk linked with a wide use of GMFs/GMOs offers the basic elements for social criticism. However, to date, it has not been justified whether the bad effects are directly resulted from products of genetic modifications or trans-genesis process. Extensive experience with the risk assessment of whole foods has been applied recently on the safety and nutritional testing of GMFs/GMOs. Investigations have tested the safety of GMFs including sub-acute, chronic, reproductive, multi-generation and carcinogenicity studies. We extrapolated the potential risks associated with GMFs/GMOs on reproduction, and analyzed the multi-aspect linked between infertility and GMFs/GMOs. It could be conjectured that GMFs/GMOs could be potential hazard on reproduction, linking to the development of infertility through influencing the endocrine metabolism, endometriosis. However, little evidence shows the impaction on embryo or reproductive related tumor due to the limited literatures, and needs further research. The article presents some related patents on GMFs/GMOs, and some methods for tracking GMOs.

Development and validation of duplex, triplex, and pentaplex real-time PCR screening assays for the detection of genetically modified organisms in food and feed.

PubMed

Huber, Ingrid; Block, Annette; Sebah, Daniela; Debode, Frédéric; Morisset, Dany; Grohmann, Lutz; Berben, Gilbert; Stebih, Dejan; Milavec, Mojca; Zel, Jana; Busch, Ulrich

2013-10-30

Worldwide, qualitative methods based on PCR are most commonly used as screening tools for genetically modified material in food and feed. However, the increasing number and diversity of genetically modified organisms (GMO) require effective methods for simultaneously detecting several genetic elements marking the presence of transgenic events. Herein we describe the development and validation of a pentaplex, as well as complementary triplex and duplex real-time PCR assays, for the detection of the most common screening elements found in commercialized GMOs: P-35S, T-nos, ctp2-cp4-epsps, bar, and pat. The use of these screening assays allows the coverage of many GMO events globally approved for commercialization. Each multiplex real-time PCR assay shows high specificity and sensitivity with an absolute limit of detection below 20 copies for the targeted sequences. We demonstrate by intra- and interlaboratory tests that the assays are robust as well as cost- and time-effective for GMO screening if applied in routine GMO analysis.

Variables Affecting Secondary School Students' Willingness to Eat Genetically Modified Food Crops

NASA Astrophysics Data System (ADS)

Maes, Jasmien; Bourgonjon, Jeroen; Gheysen, Godelieve; Valcke, Martin

2017-04-01

A large-scale cross-sectional study (N = 4002) was set up to determine Flemish secondary school students' willingness to eat genetically modified food (WTE) and to link students' WTE to previously identified key variables from research on the acceptance of genetic modification (GM). These variables include subjective and objective knowledge about genetics and biotechnology, perceived risks and benefits of GM food crops, trust in information from different sources about GM, and food neophobia. Differences between WTE-related variables based on students' grade level, educational track, and gender were analyzed. The students displayed a rather indecisive position toward GM food and scored weakly on a genetics and biotechnology knowledge test. WTE correlated most strongly with perceived benefits and subjective and objective knowledge. The results have clear implications for education, as they reiterate the need to strengthen students' scientific knowledge base and to introduce a GM-related debate at a much earlier stage in their school career.

Variables Affecting Secondary School Students' Willingness to Eat Genetically Modified Food Crops

NASA Astrophysics Data System (ADS)

Maes, Jasmien; Bourgonjon, Jeroen; Gheysen, Godelieve; Valcke, Martin

2018-06-01

A large-scale cross-sectional study ( N = 4002) was set up to determine Flemish secondary school students' willingness to eat genetically modified food (WTE) and to link students' WTE to previously identified key variables from research on the acceptance of genetic modification (GM). These variables include subjective and objective knowledge about genetics and biotechnology, perceived risks and benefits of GM food crops, trust in information from different sources about GM, and food neophobia. Differences between WTE-related variables based on students' grade level, educational track, and gender were analyzed. The students displayed a rather indecisive position toward GM food and scored weakly on a genetics and biotechnology knowledge test. WTE correlated most strongly with perceived benefits and subjective and objective knowledge. The results have clear implications for education, as they reiterate the need to strengthen students' scientific knowledge base and to introduce a GM-related debate at a much earlier stage in their school career.

Sertraline for the treatment of depression in Alzheimer disease: genetic influences.

PubMed

Peters, Matthew E; Vaidya, Vijay; Drye, Lea T; Rosenberg, Paul B; Martin, Barbara K; Porsteinsson, Anton P; Frangakis, Constantine E; Mintzer, Jacobo; Weintraub, Daniel; Schneider, Lon S; Rabins, Peter V; Munro, Cynthia A; Meinert, Curtis L; Lyketsos, Constantine G; Avramopoulos, Dimitri; Dimitri, Avramopoulos

2011-12-01

To assess the potential for genetic influences on sertraline treatment efficacy for depression of Alzheimer disease (dAD). Four functional genetic variants were studied: 2 serotonin receptors (HTR2A-T102C and HTR2C-Cys23Ser), the serotonin transporter (5HTT-LPR), and brain-derived neurotrophic factor (BDNF-Val66Met). Treatment response by genotype was measured by (1) the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change, (2) the Cornell scale for Depression in Dementia, and (3) remission of depression. We utilized data from the Depression in Alzheimer's Disease Study 2 (DIADS-2), a 24-week, randomized, multicenter trial showing no significant treatment effect of sertraline on dAD. Proportional odds logistic regression and mixed effects models were used to examine the above mentioned outcome measures. No significant interactions were seen between any of the genetic polymorphisms and the selected outcomes above at 12 or 24 weeks. Treatment outcomes in the DIADS-2 trial were not significantly influenced by genetic variation at the loci that were assessed. Future studies should continue to examine the interaction of depression-related genetic variants with antidepressant treatment in Alzheimer disease patients with depression.

Methods for identifying SNP interactions: a review on variations of Logic Regression, Random Forest and Bayesian logistic regression.

PubMed

Chen, Carla Chia-Ming; Schwender, Holger; Keith, Jonathan; Nunkesser, Robin; Mengersen, Kerrie; Macrossan, Paula

2011-01-01

Due to advancements in computational ability, enhanced technology and a reduction in the price of genotyping, more data are being generated for understanding genetic associations with diseases and disorders. However, with the availability of large data sets comes the inherent challenges of new methods of statistical analysis and modeling. Considering a complex phenotype may be the effect of a combination of multiple loci, various statistical methods have been developed for identifying genetic epistasis effects. Among these methods, logic regression (LR) is an intriguing approach incorporating tree-like structures. Various methods have built on the original LR to improve different aspects of the model. In this study, we review four variations of LR, namely Logic Feature Selection, Monte Carlo Logic Regression, Genetic Programming for Association Studies, and Modified Logic Regression-Gene Expression Programming, and investigate the performance of each method using simulated and real genotype data. We contrast these with another tree-like approach, namely Random Forests, and a Bayesian logistic regression with stochastic search variable selection.

Spatial heterogeneity and the evolution of sex in diploids.

PubMed

Agrawal, Aneil F

2009-07-01

Much of the theoretical work on the evolution of sex has focused on the effects of recombination. In diploids, segregation also occurs during sexual reproduction. Segregation breaks down some types of genetic associations that are not affected by recombination and thus influences the evolution of sex in ways that are not apparent from studying the evolution of recombination as a surrogate for sex. Here I examine the evolution of sex in diploids experiencing spatially heterogeneous selection. If divergent selection causes genetic differentiation, then migration can be a powerful force generating genetic associations that may not be favored by selection. An advantage to sex can arise from breaking down these associations. By examining modifiers of both sex and recombination, the model allows for a direct comparison of the forces acting on these related but different processes, illuminating the role of segregation. The model also includes inbreeding, which has been shown to be important for both segregation and recombination. I find that inbreeding affects the evolution of sex through segregation, not recombination. Several suggestions for empirical experiments are given.

Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

PubMed Central

Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

2014-01-01

Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

Loss-of-function of a ubiquitin-related modifier promotes the mobilization of the active MITE mPing.

PubMed

Tsukiyama, Takuji; Teramoto, Shota; Yasuda, Kanako; Horibata, Akira; Mori, Nanako; Okumoto, Yutaka; Teraishi, Masayoshi; Saito, Hiroki; Onishi, Akiko; Tamura, Kanako; Tanisaka, Takatoshi

2013-05-01

Miniature inverted-repeat transposable elements (MITEs) are widespread in both prokaryotic and eukaryotic genomes, where their copy numbers can attain several thousands. Little is known, however, about the genetic factor(s) affecting their transpositions. Here, we show that disruption of a gene encoding ubiquitin-like protein markedly enhances the transposition activity of a MITE mPing in intact rice plants without any exogenous stresses. We found that the transposition activity of mPing is far higher in the lines harboring a non-functional allele at the Rurm1 (Rice ubiquitin-related modifier-1) locus than in the wild-type line. Although the alteration of cytosine methylation pattern triggers the activation of transposable elements under exogenous stress conditions, the methylation degrees in the whole genome, the mPing-body region, and the mPing-flanking regions of the non-functional Rurm1 line were unchanged. This study provides experimental evidence for one of the models of genome shock theory that genetic accidents within cells enhance the transposition activities of transposable elements.

Driving CAR-Based T-Cell Therapy to Success

PubMed Central

Jena, Bipulendu; Moyes, Judy S; Huls, Helen; Cooper, Laurence JN

2014-01-01

T-cells that have been genetically modified, activated, and propagated ex vivo can be infused to control tumor progression in patients who are refractory to conventional treatments. Early-phase clinical trials demonstrate that the tumor-associated antigen (TAA) CD19 can be therapeutically engaged through the enforced expression of a chimeric antigen receptor (CAR) on clinical-grade T-cells. Advances in vector design, the architecture of the CAR molecule especially as associated with T-cell co-stimulatory pathways, and understanding of the tumor microenvironment, play significant roles in the successful treatment of medically fragile patients. However, some recipients of CAR+ T-cells demonstrate incomplete responses. Understanding the potential for treatment failure provides a pathway to improve the potency of adoptive transfer of CAR+ T-cells. High throughput single-cell analyses to understand the complexity of the inoculum coupled with animal models may provide insight into the therapeutic potential of genetically modified T-cells. This review focusses on recent advances regarding the human application of C19-specific CAR+ T-cells and explores how their success for hematologic cancers can provide a framework for investigational treatment of solid tumor malignancies. PMID:24488441

The Flipside of the Power of Engineered T Cells: Observed and Potential Toxicities of Genetically Modified T Cells as Therapy.

PubMed

Bedoya, Felipe; Frigault, Matthew J; Maus, Marcela V

2017-02-01

Autologous T cells modified to recognize novel antigen targets are a novel form of therapy for cancer. We review the various potential forms of observed and hypothetical toxicities associated with genetically modified T cells. Despite the focus on toxicities in this review, re-directed T cells represent a powerful and highly effective form of anti-cancer therapy; we remain optimistic that the common toxicities will become routinely manageable and that some theoretical toxicity will be exceedingly rare, if ever observed. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

CARs: Driving T-cell specificity to enhance anti-tumor immunity

PubMed Central

Kebriaei, Partow; Kelly, Susan S.; Manuri, Pallavi; Jena, Bipulendu; Jackson, Rineka; Shpall, Elizabeth; Champlin, Richard; Cooper, Laurence J. N.

2013-01-01

Adoptive transfer of antigen-specific T cells is a compelling tool to treat cancer. To overcome issues of immune tolerance which limits the endogenous adaptive immune response to tumor-associated antigens, robust systems for the genetic modification and characterization of T cells expressing chimeric antigen receptors (CARs) to redirect specificity have been produced. Refinements with regards to persistence and trafficking of the genetically modified T cells are underway to help improve the potency of genetically modified T cells. Clinical trials utilizing this technology demonstrate feasibility, and increasingly, antitumor activity, paving the way for multi-center trials to establish the efficacy of this novel T-cell therapy. PMID:22202074

Cost-effectiveness of MODY genetic testing: translating genomic advances into practical health applications.

PubMed

Naylor, Rochelle N; John, Priya M; Winn, Aaron N; Carmody, David; Greeley, Siri Atma W; Philipson, Louis H; Bell, Graeme I; Huang, Elbert S

2014-01-01

OBJECTIVE To evaluate the cost-effectiveness of a genetic testing policy for HNF1A-, HNF4A-, and GCK-MODY in a hypothetical cohort of type 2 diabetic patients 25-40 years old with a MODY prevalence of 2%. RESEARCH DESIGN AND METHODS We used a simulation model of type 2 diabetes complications based on UK Prospective Diabetes Study data, modified to account for the natural history of disease by genetic subtype to compare a policy of genetic testing at diabetes diagnosis versus a policy of no testing. Under the screening policy, successful sulfonylurea treatment of HNF1A-MODY and HNF4A-MODY was modeled to produce a glycosylated hemoglobin reduction of -1.5% compared with usual care. GCK-MODY received no therapy. Main outcome measures were costs and quality-adjusted life years (QALYs) based on lifetime risk of complications and treatments, expressed as the incremental cost-effectiveness ratio (ICER) (USD/QALY). RESULTS The testing policy yielded an average gain of 0.012 QALYs and resulted in an ICER of 205,000 USD. Sensitivity analysis showed that if the MODY prevalence was 6%, the ICER would be ~50,000 USD. If MODY prevalence was >30%, the testing policy was cost saving. Reducing genetic testing costs to 700 USD also resulted in an ICER of ~50,000 USD. CONCLUSIONS Our simulated model suggests that a policy of testing for MODY in selected populations is cost-effective for the U.S. based on contemporary ICER thresholds. Higher prevalence of MODY in the tested population or decreased testing costs would enhance cost-effectiveness. Our results make a compelling argument for routine coverage of genetic testing in patients with high clinical suspicion of MODY.

Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.

PubMed

Walker, Celia G; Solis-Trapala, Ivonne; Holzapfel, Christina; Ambrosini, Gina L; Fuller, Nicholas R; Loos, Ruth J F; Hauner, Hans; Caterson, Ian D; Jebb, Susan A

2015-01-01

The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.

Kidney disease models: tools to identify mechanisms and potential therapeutic targets

PubMed Central

Bao, Yin-Wu; Yuan, Yuan; Chen, Jiang-Hua; Lin, Wei-Qiang

2018-01-01

Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy. In this review, we discuss AKI models induced by surgical operation and drugs or toxins, as well as a variety of CKD models (mainly genetically modified mouse models). Results from recent and ongoing clinical trials and conceptual advances derived from animal models are also explored. PMID:29515089

Evaluation of the information content of long-term wastewater characteristics data in relation to activated sludge model parameters.

PubMed

Alikhani, Jamal; Takacs, Imre; Al-Omari, Ahmed; Murthy, Sudhir; Massoudieh, Arash

2017-03-01

A parameter estimation framework was used to evaluate the ability of observed data from a full-scale nitrification-denitrification bioreactor to reduce the uncertainty associated with the bio-kinetic and stoichiometric parameters of an activated sludge model (ASM). Samples collected over a period of 150 days from the effluent as well as from the reactor tanks were used. A hybrid genetic algorithm and Bayesian inference were used to perform deterministic and parameter estimations, respectively. The main goal was to assess the ability of the data to obtain reliable parameter estimates for a modified version of the ASM. The modified ASM model includes methylotrophic processes which play the main role in methanol-fed denitrification. Sensitivity analysis was also used to explain the ability of the data to provide information about each of the parameters. The results showed that the uncertainty in the estimates of the most sensitive parameters (including growth rate, decay rate, and yield coefficients) decreased with respect to the prior information.

Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction.

PubMed

Paul, Arghya; Nayan, Madhur; Khan, Afshan Afsar; Shum-Tim, Dominique; Prakash, Satya

2012-01-01

The objective of this study was to develop angiopoietin-1 (Ang1)-expressing genetically modified human adipose tissue derived stem cells (hASCs) for myocardial therapy. For this, an efficient gene delivery system using recombinant baculovirus complexed with cell penetrating transactivating transcriptional activator TAT peptide/deoxyribonucleic acid nanoparticles (Bac-NP), through ionic interactions, was used. It was hypothesized that the hybrid Bac- NP(Ang1) system can efficiently transduce hASCs and induces favorable therapeutic effects when transplanted in vivo. To evaluate this hypothesis, a rat model with acute myocardial infarction and intramyocardially transplanted Ang1-expressing hASCs (hASC-Ang1), genetically modified by Bac-NP(Ang1), was used. Ang1 is a crucial pro-angiogenic factor for vascular maturation and neovasculogenesis. The released hAng1 from hASC-Ang1 demonstrated profound mitotic and anti-apoptotic activities on endothelial cells and cardiomyocytes. The transplanted hASC-Ang1 group showed higher cell retention compared to hASC and control groups. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with hASC-Ang1 treatment compared to infarcted hearts treated with hASC or the untreated group. Furthermore, the hASC-Ang1 group showed significantly higher cardiac performance in echocardiography (ejection fraction 46.28% ± 6.3%, P < 0.001 versus control, n = 8) than the hASC group (36.35% ± 5.7%, P < 0.01, n = 8), 28 days post-infarction. The study identified Bac-NP complex as an advanced gene delivery vehicle for stem cells and demonstrated its potential to treat ischemic heart disease with high therapeutic index for combined stem cell-gene therapy strategy.

Solid, liquid, and interfacial properties of TiAl alloys: parameterization of a new modified embedded atom method model

NASA Astrophysics Data System (ADS)

Sun, Shoutian; Ramu Ramachandran, Bala; Wick, Collin D.

2018-02-01

New interatomic potentials for pure Ti and Al, and binary TiAl were developed utilizing the second nearest neighbour modified embedded-atom method (MEAM) formalism. The potentials were parameterized to reproduce multiple properties spanning bulk solids, solid surfaces, solid/liquid phase changes, and liquid interfacial properties. This was carried out using a newly developed optimization procedure that combined the simple minimization of a fitness function with a genetic algorithm to efficiently span the parameter space. The resulting MEAM potentials gave good agreement with experimental and DFT solid and liquid properties, and reproduced the melting points for Ti, Al, and TiAl. However, the surface tensions from the model consistently underestimated experimental values. Liquid TiAl’s surface was found to be mostly covered with Al atoms, showing that Al has a significant propensity for the liquid/air interface.

Modified Mahalanobis Taguchi System for Imbalance Data Classification

PubMed Central

2017-01-01

The Mahalanobis Taguchi System (MTS) is considered one of the most promising binary classification algorithms to handle imbalance data. Unfortunately, MTS lacks a method for determining an efficient threshold for the binary classification. In this paper, a nonlinear optimization model is formulated based on minimizing the distance between MTS Receiver Operating Characteristics (ROC) curve and the theoretical optimal point named Modified Mahalanobis Taguchi System (MMTS). To validate the MMTS classification efficacy, it has been benchmarked with Support Vector Machines (SVMs), Naive Bayes (NB), Probabilistic Mahalanobis Taguchi Systems (PTM), Synthetic Minority Oversampling Technique (SMOTE), Adaptive Conformal Transformation (ACT), Kernel Boundary Alignment (KBA), Hidden Naive Bayes (HNB), and other improved Naive Bayes algorithms. MMTS outperforms the benchmarked algorithms especially when the imbalance ratio is greater than 400. A real life case study on manufacturing sector is used to demonstrate the applicability of the proposed model and to compare its performance with Mahalanobis Genetic Algorithm (MGA). PMID:28811820

Solid, liquid, and interfacial properties of TiAl alloys: parameterization of a new modified embedded atom method model.

PubMed

Sun, Shoutian; Ramachandran, Bala Ramu; Wick, Collin D

2018-02-21

New interatomic potentials for pure Ti and Al, and binary TiAl were developed utilizing the second nearest neighbour modified embedded-atom method (MEAM) formalism. The potentials were parameterized to reproduce multiple properties spanning bulk solids, solid surfaces, solid/liquid phase changes, and liquid interfacial properties. This was carried out using a newly developed optimization procedure that combined the simple minimization of a fitness function with a genetic algorithm to efficiently span the parameter space. The resulting MEAM potentials gave good agreement with experimental and DFT solid and liquid properties, and reproduced the melting points for Ti, Al, and TiAl. However, the surface tensions from the model consistently underestimated experimental values. Liquid TiAl's surface was found to be mostly covered with Al atoms, showing that Al has a significant propensity for the liquid/air interface.

Optimisation of assembly scheduling in VCIM systems using genetic algorithm

NASA Astrophysics Data System (ADS)

Dao, Son Duy; Abhary, Kazem; Marian, Romeo

2017-09-01

Assembly plays an important role in any production system as it constitutes a significant portion of the lead time and cost of a product. Virtual computer-integrated manufacturing (VCIM) system is a modern production system being conceptually developed to extend the application of traditional computer-integrated manufacturing (CIM) system to global level. Assembly scheduling in VCIM systems is quite different from one in traditional production systems because of the difference in the working principles of the two systems. In this article, the assembly scheduling problem in VCIM systems is modeled and then an integrated approach based on genetic algorithm (GA) is proposed to search for a global optimised solution to the problem. Because of dynamic nature of the scheduling problem, a novel GA with unique chromosome representation and modified genetic operations is developed herein. Robustness of the proposed approach is verified by a numerical example.

Quadratic genetic modifications: a streamlined route to cosmological simulations with controlled merger history

NASA Astrophysics Data System (ADS)

Rey, Martin P.; Pontzen, Andrew

2018-02-01

Recent work has studied the interplay between a galaxy's history and its observable properties using `genetically modified' cosmological zoom simulations. The approach systematically generates alternative histories for a halo, while keeping its cosmological environment fixed. Applications to date altered linear properties of the initial conditions, such as the mean overdensity of specified regions; we extend the formulation to include quadratic features, such as local variance, that determines the overall importance of smooth accretion relative to mergers in a galaxy's history. We introduce an efficient algorithm for this new class of modification and demonstrate its ability to control the variance of a region in a one-dimensional toy model. Outcomes of this work are twofold: (i) a clarification of the formulation of genetic modifications and (ii) a proof of concept for quadratic modifications leading the way to a forthcoming implementation in cosmological simulations.

Genetically modified proteins: functional improvement and chimeragenesis

PubMed Central

Balabanova, Larissa; Golotin, Vasily; Podvolotskaya, Anna; Rasskazov, Valery

2015-01-01

This review focuses on the emerging role of site-specific mutagenesis and chimeragenesis for the functional improvement of proteins in areas where traditional protein engineering methods have been extensively used and practically exhausted. The novel path for the creation of the novel proteins has been created on the farther development of the new structure and sequence optimization algorithms for generating and designing the accurate structure models in result of x-ray crystallography studies of a lot of proteins and their mutant forms. Artificial genetic modifications aim to expand nature's repertoire of biomolecules. One of the most exciting potential results of mutagenesis or chimeragenesis finding could be design of effective diagnostics, bio-therapeutics and biocatalysts. A sampling of recent examples is listed below for the in vivo and in vitro genetically improvement of various binding protein and enzyme functions, with references for more in-depth study provided for the reader's benefit. PMID:26211369

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

PubMed

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B; Rudolph, Anja; Schmutzler, Rita K; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A; Easton, Douglas F; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A; Schmidt, Marjanka K; van der Baan, Frederieke H; Spurdle, Amanda B; Walker, Logan C; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B; Olopade, Olufunmilayo I; Nussbaum, Robert L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Karlan, Beth Y; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K; Miron, Alex; Southey, Melissa C; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E; Blazer, Kathleen R; Weitzel, Jeffrey N; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D Gareth R; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V; Ellis, Steve; Cole, Trevor; Godwin, Andrew K; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L; Rodriguez, Gustavo C; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A M; Meijers-Heijboer, Hanne E J; van der Hout, Annemarie H; Vreeswijk, Maaike P G; Hoogerbrugge, Nicoline; Ausems, Margreet G E M; van Doorn, Helena C; Collée, J Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R; Olswold, Curtis; Couch, Fergus J; Lindor, Noralane M; Wang, Xianshu; Szabo, Csilla I; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C; Friedman, Eitan

2015-01-01

BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. ©2014 American Association for Cancer Research.

Animal models to detect allergenicity to foods and genetically modified products: workshop summary.

PubMed Central

Tryphonas, Helen; Arvanitakis, George; Vavasour, Elizabeth; Bondy, Genevieve

2003-01-01

Respiratory allergy and allergy to foods continue to be important health issues. There is evidence to indicate that the incidence of food allergy around the world is on the rise. Current estimates indicate that approximately 5% of young children and 1-2% of adults suffer from true food allergy (Kagan 2003). Although a large number of in vivo and in vitro tests exist for the clinical diagnosis of allergy in humans, we lack validated animal models of allergenicity. This deficiency creates serious problems for regulatory agencies and industries that must define the potential allergenicity of foods before marketing. The emergence of several biotechnologically derived foods and industrial proteins, as well as their potential to sensitize genetically predisposed populations to develop allergy, has prompted health officials and regulatory agencies around the world to seek approaches and methodologies to screen novel proteins for allergenicity. PMID:12573909

Genetically modified pigs produced with a nonviral episomal vector

PubMed Central

Manzini, Stefano; Vargiolu, Alessia; Stehle, Isa M; Bacci, Maria Laura; Cerrito, Maria Grazia; Giovannoni, Roberto; Zannoni, Augusta; Bianco, Maria Rosaria; Forni, Monica; Donini, Pierluigi; Papa, Michele; Lipps, Hans J; Lavitrano, Marialuisa

2006-01-01

Genetic modification of cells and animals is an invaluable tool for biotechnology and biomedicine. Currently, integrating vectors are used for this purpose. These vectors, however, may lead to insertional mutagenesis and variable transgene expression and can undergo silencing. Scaffold/matrix attachment region-based vectors are nonviral expression systems that replicate autonomously in mammalian cells, thereby making possible safe and reliable genetic modification of higher eukaryotic cells and organisms. In this study, genetically modified pig fetuses were produced with the scaffold/matrix attachment region-based vector pEPI, delivered to embryos by the sperm-mediated gene transfer method. The pEPI vector was detected in 12 of 18 fetuses in the different tissues analyzed and was shown to be retained as an episome. The reporter gene encoded by the pEPI vector was expressed in 9 of 12 genetically modified fetuses. In positive animals, all tissues analyzed expressed the reporter gene; moreover in these tissues, the positive cells were on the average 79%. The high percentage of EGFP-expressing cells and the absence of mosaicism have important implications for biotechnological and biomedical applications. These results are an important step forward in animal transgenesis and can provide the basis for the future development of germ-line gene therapy. PMID:17101993

Environmental stress alters genetic regulation of novelty seeking in vervet monkeys.

PubMed

Fairbanks, L A; Bailey, J N; Breidenthal, S E; Laudenslager, M L; Kaplan, J R; Jorgensen, M J

2011-08-01

Considerable attention has been paid to identifying genetic influences and gene-environment interactions that increase vulnerability to environmental stressors, with promising but inconsistent results. A nonhuman primate model is presented here that allows assessment of genetic influences in response to a stressful life event for a behavioural trait with relevance for psychopathology. Genetic and environmental influences on free-choice novelty seeking behaviour were assessed in a pedigreed colony of vervet monkeys before and after relocation from a low stress to a higher stress environment. Heritability of novelty seeking scores, and genetic correlations within and between environments were conducted using variance components analysis. The results showed that novelty seeking was markedly inhibited in the higher stress environment, with effects persisting across a 2-year period for adults but not for juveniles. There were significant genetic contributions to novelty seeking scores in each year (h(2) = 0.35-0.43), with high genetic correlations within each environment (rhoG > 0.80) and a lower genetic correlation (rhoG = 0.35, non-significant) between environments. There were also significant genetic contributions to individual change scores from before to after the move (h(2) = 0.48). These results indicate that genetic regulation of novelty seeking was modified by the level of environmental stress, and they support a role for gene-environment interactions in a behavioural trait with relevance for mental health. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Genetically engineered plants with increased vegetative oil content

DOEpatents

Benning, Christoph

2017-05-23

The invention relates to genetically modified agricultural plants with increased oil content in vegetative tissues, as well as to expression systems, plant cells, seeds and vegetative tissues related thereto.

Frankenfoods: Values about Genetics Embedded in a Metaphor.

ERIC Educational Resources Information Center

Flores, Vanessa S.; Tobin, Allan J.

2002-01-01

Presents an assay on genetically modified (GM) foods, also called Frankenfoods, that demonstrates ways to evaluate a scientific metaphor and facilitate discussion on students' values regarding GM foods. (YDS)

Cry1A(b)16 toxin from Bacillus thuringiensis: Theoretical refinement of three-dimensional structure and prediction of peptides as molecular markers for detection of genetically modified organisms.

PubMed

Plácido, Alexandra; Coelho, Andreia; Abreu Nascimento, Lucas; Gomes Vasconcelos, Andreanne; Fátima Barroso, Maria; Ramos-Jesus, Joilson; Costa, Vladimir; das Chagas Alves Lima, Francisco; Delerue-Matos, Cristina; Martins Ramos, Ricardo; Marani, Mariela M; Roberto de Souza de Almeida Leite, José

2017-07-01

Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, for example, biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures. Molecular dynamics simulations were carried out to refine the selected model, and an analysis of its global structure was performed. The refined models of Cry1A(b)16 showed a standard fold and structural characteristics similar to those seen in Bacillus thuringiensis Cry1A(a) insecticidal toxin and Bacillus thuringiensis serovar kurstaki Cry1A(c) toxin. After in silico analysis of Cry1A(b)16, two immunoreactive candidate peptides were selected and specific polyclonal antibodies were produced resulting in antibody-peptide interaction. Biosensing devices are expected to be developed for detection of the Cry1A(b) protein as a marker of transgenic maize in food. Proteins 2017; 85:1248-1257. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Current perspectives on genetically modified crops and detection methods.

PubMed

Kamle, Madhu; Kumar, Pradeep; Patra, Jayanta Kumar; Bajpai, Vivek K

2017-07-01

Genetically modified (GM) crops are the fastest adopted commodities in the agribiotech industry. This market penetration should provide a sustainable basis for ensuring food supply for growing global populations. The successful completion of two decades of commercial GM crop production (1996-2015) is underscored by the increasing rate of adoption of genetic engineering technology by farmers worldwide. With the advent of introduction of multiple traits stacked together in GM crops for combined herbicide tolerance, insect resistance, drought tolerance or disease resistance, the requirement of reliable and sensitive detection methods for tracing and labeling genetically modified organisms in the food/feed chain has become increasingly important. In addition, several countries have established threshold levels for GM content which trigger legally binding labeling schemes. The labeling of GM crops is mandatory in many countries (such as China, EU, Russia, Australia, New Zealand, Brazil, Israel, Saudi Arabia, Korea, Chile, Philippines, Indonesia, Thailand), whereas in Canada, Hong Kong, USA, South Africa, and Argentina voluntary labeling schemes operate. The rapid adoption of GM crops has increased controversies, and mitigating these issues pertaining to the implementation of effective regulatory measures for the detection of GM crops is essential. DNA-based detection methods have been successfully employed, while the whole genome sequencing using next-generation sequencing (NGS) technologies provides an advanced means for detecting genetically modified organisms and foods/feeds in GM crops. This review article describes the current status of GM crop commercialization and discusses the benefits and shortcomings of common and advanced detection systems for GMs in foods and animal feeds.

Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control and Vascular Events in Atrial Fibrillation.

PubMed

Park, Yun Kyung; Lee, Mi Ji; Kim, Jae Ha; Lee, Jin Soo; Park, Rae Woong; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Kim, June Soo; Lee, Soo-Youn; Bang, Oh Young

2017-06-01

Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years. We evaluated the factors associated with time in therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin dose assessment interval). The genotypic frequency of CYP2C9*3 (rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1 1173C>T than of the VKORC1 TT genotype (61.7 ± 16.0% versus 56.7 ± 17.4%, P = .031). Multivariate testing showed that the VKORC1 genotype and anticoagulation service were independently related to labile INRs (TTR <65%). Vascular events were observed in 66 patients (18.4%) during the study period. A Cox proportional hazard model showed that the use of anticoagulation service and patients' characteristics, such as AF-thromboembolic risk (CHA 2 DS 2 -VASc score: Congestive heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years, female) and consequence (neurologic disability), but not genetic factors, were independently associated with vascular events. Both genetic factor (VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the quality of anticoagulation control. However, clinical events were more strongly associated with patient characteristics and clinical efforts than with genetic factors. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Microorganisms having enhanced tolerance to inhibitors and stress

DOEpatents

Brown, Steven D.; Yang, Shihui

2014-07-29

The present invention provides genetically modified strains of microorganisms that display enhanced tolerance to stress and/or inhibitors such as sodium acetate and vanillin. The enhanced tolerance can be achieved by increasing the expression of a protein of the Sm-like superfamily such as a bacterial Hfq protein and a fungal Sm or Lsm protein. Further, the present invention provides methods of producing alcohol from biomass materials by using the genetically modified microorganisms of the present invention.

The use of life-cycle assessment to evaluate the environmental impacts of growing genetically modified, nitrogen use-efficient canola.

PubMed

Strange, Alison; Park, Julian; Bennett, Richard; Phipps, Richard

2008-05-01

Agriculture, particularly intensive crop production, makes a significant contribution to environmental pollution. A variety of canola (Brassica napus) has been genetically modified to enhance nitrogen use efficiency, effectively reducing the amount of fertilizer required for crop production. A partial life-cycle assessment adapted to crop production was used to assess the potential environmental impacts of growing genetically modified, nitrogen use-efficient (GMNUE) canola in North Dakota and Minnesota compared with a conventionally bred control variety. The analysis took into account the entire production system used to produce 1 tonne of canola. This comprised raw material extraction, processing and transportation, as well as all agricultural field operations. All emissions associated with the production of 1 tonne of canola were listed, aggregated and weighted in order to calculate the level of environmental impact. The findings show that there are a range of potential environmental benefits associated with growing GMNUE canola. These include reduced impacts on global warming, freshwater ecotoxicity, eutrophication and acidification. Given the large areas of canola grown in North America and, in particular, Canada, as well as the wide acceptance of genetically modified varieties in this area, there is the potential for GMNUE canola to reduce pollution from agriculture, with the largest reductions predicted to be in greenhouse gases and diffuse water pollution.

[Contamination with genetically modified maize MON863 of processed foods on the market].

PubMed

Ohgiya, Yoko; Sakai, Masaaki; Miyashita, Taeko; Yano, Koichi

2009-06-01

Genetically modified maize MON863 (MON863), which has passed a safety examination in Japan, is commercially cultivated in the United States as a food and a resource for fuel. Maize is an anemophilous flower, which easily hybridizes. However, an official method for quantifying the content of MON863 has not been provided yet in Japan. We here examined MON863 contamination in maize-processed foods that had no labeling indicating of the use of genetically modified maize.From March 2006 to July 2008, we purchased 20 frozen maize products, 8 maize powder products, 7 canned maize products and 4 other maize processed foods. Three primer pairs named MON 863 primer, MON863-1, and M3/M4 for MON863-specific integrated cassette were used for qualitative polymerase chain reaction (PCR). A primer pair "SSIIb-3" for starch synthase gene was used to confirm the quality of extracted DNA. The starch synthase gene was detected in all samples. In qualitative tests, the MON863-specific fragments were detected in 7 (18%) maize powder products out of the 39 processed foods with all the three primer pairs.We concluded that various maize processed foods on the market were contaminated with MON863. It is important to accumulate further information on MON863 contamination in maize-processed foods that have no label indication of the use of genetically modified maize.

Genetic mouse models of brain ageing and Alzheimer's disease.

PubMed

Bilkei-Gorzo, Andras

2014-05-01

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

PubMed Central

Homburger, Julian R.; Green, Eric M.; Caleshu, Colleen; Sunitha, Margaret S.; Taylor, Rebecca E.; Ruppel, Kathleen M.; Metpally, Raghu Prasad Rao; Colan, Steven D.; Michels, Michelle; Day, Sharlene M.; Olivotto, Iacopo; Bustamante, Carlos D.; Dewey, Frederick E.; Ho, Carolyn Y.; Spudich, James A.; Ashley, Euan A.

2016-01-01

Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

Mechanisms underlying the lifetime co-occurrence of tobacco and cannabis use in adolescent and young adult twins

PubMed Central

Agrawal, Arpana; Silberg, Judy L.; Lynskey, Michael T.; Maes, Hermine H.; Eaves, Lindon J.

2009-01-01

Using twins assessed during adolescence (Virginia Twin Study of Adolescent Behavioral Development: 8–17 years) and followed up in early adulthood (Young Adult Follow-Up, 18–27 years), we tested 13 genetically informative models of co-occurrence, adapted for the inclusion of covariates. Models were fit, in Mx, to data at both assessments allowing for a comparison of the mechanisms that underlie the lifetime co-occurrence of cannabis and tobacco use in adolescence and early adulthood. Both cannabis and tobacco use were influenced by additive genetic (38–81%) and non-shared environmental factors with the possible role of non-shared environment in the adolescent assessment only. Causation models, where liability to use cannabis exerted a causal influence on the liability to use tobacco fit the adolescent data best, while the reverse causation model (tobacco causes cannabis) fit the early adult data best. Both causation models (cannabis to tobacco and tobacco to cannabis) and the correlated liabilities model fit data from the adolescent and young adult assessments well. Genetic correlations (0.59–0.74) were moderate. Therefore, the relationship between cannabis and tobacco use is fairly similar during adolescence and early adulthood with reciprocal influences across the two psychoactive substances. However, our study could not exclude the possibility that ‘gateways’ and ‘reverse gateways’, particularly within a genetic context, exist, such that predisposition to using one substance (cannabis or tobacco) modifies predisposition to using the other. Given the high addictive potential of nicotine and the ubiquitous nature of cannabis use, this is a public health concern worthy of considerable attention. PMID:20047801

Mediation and modification of genetic susceptibility to obesity by eating behaviors.

PubMed

de Lauzon-Guillain, Blandine; Clifton, Emma Ad; Day, Felix R; Clément, Karine; Brage, Soren; Forouhi, Nita G; Griffin, Simon J; Koudou, Yves Akoli; Pelloux, Véronique; Wareham, Nicholas J; Charles, Marie-Aline; Heude, Barbara; Ong, Ken K

2017-10-01

Background: Many genetic variants show highly robust associations with body mass index (BMI). However, the mechanisms through which genetic susceptibility to obesity operates are not well understood. Potentially modifiable mechanisms, including eating behaviors, are of particular interest to public health. Objective: Here we explore whether eating behaviors mediate or modify genetic susceptibility to obesity. Design: Genetic risk scores for BMI (BMI-GRSs) were calculated for 3515 and 2154 adults in the Fenland and EDEN (Etude des déterminants pré et postnatals de la santé et du développement de l'enfant) population-based cohort studies, respectively. The eating behaviors-emotional eating, uncontrolled eating, and cognitive restraint-were measured through the use of a validated questionnaire. The mediating effect of each eating behavior on the association between the BMI-GRS and measured BMI was assessed by using the Sobel test. In addition, we tested for interactions between each eating behavior and the BMI-GRS on BMI. Results: The association between the BMI-GRS and BMI was mediated by both emotional eating (EDEN: P- Sobel = 0.01; Fenland: P- Sobel = 0.02) and uncontrolled eating (EDEN: P- Sobel = 0.04; Fenland: P -Sobel = 0.0006) in both sexes combined. Cognitive restraint did not mediate this association ( P -Sobel > 0.10), except among EDEN women ( P -Sobel = 0.0009). Cognitive restraint modified the relation between the BMI-GRS and BMI among men (EDEN: P -interaction = 0.0001; Fenland: P -interaction = 0.04) and Fenland women ( P -interaction = 0.0004). By tertiles of cognitive restraint, the association between the BMI-GRS and BMI was strongest in the lowest tertile of cognitive restraint, and weakest in the highest tertile. Conclusions: Genetic susceptibility to obesity was partially mediated by the "appetitive" eating behavior traits (uncontrolled and emotional eating) and, in 3 of the 4 population groups studied, was modified by cognitive restraint. High levels of cognitive control over eating appear to attenuate the genetic susceptibility to obesity. Future research into interventions designed to support restraint may help to protect genetically susceptible individuals from weight gain. © 2017 American Society for Nutrition.

Understanding of Genetic Information in Higher Secondary Students in Northeast India and the Implications for Genetics Education

ERIC Educational Resources Information Center

Chattopadhyay, Ansuman

2005-01-01

Since the work of Watson and Crick in the mid-1950s, the science of genetics has become increasingly molecular. The development of recombinant DNA technologies by the agricultural and pharmaceutical industries led to the introduction of genetically modified organisms (GMOs). By the end of the twentieth century, reports of animal cloning and recent…

Sporophytic self-incompatibility in Senecio squalidus (Asteraceae): S allele dominance interactions and modifiers of cross-compatibility and selfing rates

PubMed Central

Brennan, A C; Tabah, D A; Harris, S A; Hiscock, S J

2011-01-01

Understanding genetic mechanisms of self-incompatibility (SI) and how they evolve is central to understanding the mating behaviour of most outbreeding angiosperms. Sporophytic SI (SSI) is controlled by a single multi-allelic locus, S, which is expressed in the diploid (sporophyte) plant to determine the SI phenotype of its haploid (gametophyte) pollen. This allows complex patterns of independent S allele dominance interactions in male (pollen) and female (pistil) reproductive tissues. Senecio squalidus is a useful model for studying the genetic regulation and evolution of SSI because of its population history as an alien invasive species in the UK. S. squalidus maintains a small number of S alleles (7–11) with a high frequency of dominance interactions. Some S. squalidus individuals also show partial selfing and/or greater levels of cross-compatibility than expected under SSI. We previously speculated that these might be adaptations to invasiveness. Here we describe a detailed characterization of the regulation of SSI in S. squalidus. Controlled crosses were used to determine the S allele dominance hierarchy of six S alleles and effects of modifiers on cross-compatibility and partial selfing. Complex dominance interactions among S alleles were found with at least three levels of dominance and tissue-specific codominance. Evidence for S gene modifiers that increase selfing and/or cross-compatibility was also found. These empirical findings are discussed in the context of theoretical predictions for maintenance of S allele dominance interactions, and the role of modifier loci in the evolution of SI. PMID:20372180

Sporophytic self-incompatibility in Senecio squalidus (Asteraceae): S allele dominance interactions and modifiers of cross-compatibility and selfing rates.

PubMed

Brennan, A C; Tabah, D A; Harris, S A; Hiscock, S J

2011-01-01

Understanding genetic mechanisms of self-incompatibility (SI) and how they evolve is central to understanding the mating behaviour of most outbreeding angiosperms. Sporophytic SI (SSI) is controlled by a single multi-allelic locus, S, which is expressed in the diploid (sporophyte) plant to determine the SI phenotype of its haploid (gametophyte) pollen. This allows complex patterns of independent S allele dominance interactions in male (pollen) and female (pistil) reproductive tissues. Senecio squalidus is a useful model for studying the genetic regulation and evolution of SSI because of its population history as an alien invasive species in the UK. S. squalidus maintains a small number of S alleles (7-11) with a high frequency of dominance interactions. Some S. squalidus individuals also show partial selfing and/or greater levels of cross-compatibility than expected under SSI. We previously speculated that these might be adaptations to invasiveness. Here we describe a detailed characterization of the regulation of SSI in S. squalidus. Controlled crosses were used to determine the S allele dominance hierarchy of six S alleles and effects of modifiers on cross-compatibility and partial selfing. Complex dominance interactions among S alleles were found with at least three levels of dominance and tissue-specific codominance. Evidence for S gene modifiers that increase selfing and/or cross-compatibility was also found. These empirical findings are discussed in the context of theoretical predictions for maintenance of S allele dominance interactions, and the role of modifier loci in the evolution of SI.

Determining which phenotypes underlie a pleiotropic signal

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Witte, John S.

2016-01-01

Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset-based meta-analysis ASSET [Bhattacharjee et al., 2012], which provides an optimal subset of non-null traits. And the third is a modified Benjamini-Hochberg (B-H) procedure of controlling the expected false discovery rate [Benjamini and Hochberg, 1995] in the framework of phenome-wide association study. From our simulations we see that an inverse regression based approach MultiPhen [O’Reilly et al., 2012] is more powerful than ASSET for detecting overall pleiotropic association, except for when all the phenotypes are associated and have genetic effects in the same direction. For determining which specific traits are pleiotropic, the modified B-H procedure performs consistently better than the other two methods. The inverse regression based selection methods perform competitively with the modified B-H procedure only when the phenotypes are weakly correlated. The efficiency of ASSET is observed to lie below and in between the efficiency of the other two methods when the traits are weakly and strongly correlated, respectively. In our application to a large GWAS, we find that the modified B-H procedure also performs well, indicating that this may be an optimal approach for determining the traits underlying a pleiotropic signal. PMID:27238845

Genetic structure and gene flow among Brazilian populations of Heliothis virescens (F.) (Lepidoptera: Noctuidae)

USDA-ARS?s Scientific Manuscript database

Population genetic studies are essential to the better application of pest management strategies, including the monitoring of the evolution of resistance to insecticides and genetically modified plants. Bt-crops have been instrumental in controlling Heliothis virescens (F.), a pest that has develop...

Learning Intelligent Genetic Algorithms Using Japanese Nonograms

ERIC Educational Resources Information Center

Tsai, Jinn-Tsong; Chou, Ping-Yi; Fang, Jia-Cen

2012-01-01

An intelligent genetic algorithm (IGA) is proposed to solve Japanese nonograms and is used as a method in a university course to learn evolutionary algorithms. The IGA combines the global exploration capabilities of a canonical genetic algorithm (CGA) with effective condensed encoding, improved fitness function, and modified crossover and…

Genetically altered mice for evaluation of mode-of-action (MOA)

EPA Science Inventory

Genetically altered mice for evaluation of mode-of-action (MOA). Barbara D. Abbott, Cynthia J. Wolf, Kaberi P. Das, Christopher S. Lau. (Presented by B. Abbott). This presentation provides an example of the use of genetically modified mice to determine the mode-of-action of r...

Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis.

PubMed

Larsson, Susanna C; Traylor, Matthew; Malik, Rainer; Dichgans, Martin; Burgess, Stephen; Markus, Hugh S

2017-12-06

To determine which potentially modifiable risk factors, including socioeconomic, lifestyle/dietary, cardiometabolic, and inflammatory factors, are associated with Alzheimer's disease. Mendelian randomisation study using genetic variants associated with the modifiable risk factors as instrumental variables. International Genomics of Alzheimer's Project. 17 008 cases of Alzheimer's disease and 37 154 controls. Odds ratio of Alzheimer's per genetically predicted increase in each modifiable risk factor estimated with Mendelian randomisation analysis. This study included analyses of 24 potentially modifiable risk factors. A Bonferroni corrected threshold of P=0.002 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. Genetically predicted educational attainment was significantly associated with Alzheimer's. The odds ratios were 0.89 (95% confidence interval 0.84 to 0.93; P=2.4×10 -6 ) per year of education completed and 0.74 (0.63 to 0.86; P=8.0×10 -5 ) per unit increase in log odds of having completed college/university. The correlated trait intelligence had a suggestive association with Alzheimer's (per genetically predicted 1 SD higher intelligence: 0.73, 0.57 to 0.93; P=0.01). There was suggestive evidence for potential associations between genetically predicted higher quantity of smoking (per 10 cigarettes a day: 0.69, 0.49 to 0.99; P=0.04) and 25-hydroxyvitamin D concentrations (per 20% higher levels: 0.92, 0.85 to 0.98; P=0.01) and lower odds of Alzheimer's and between higher coffee consumption (per one cup a day: 1.26, 1.05 to 1.51; P=0.01) and higher odds of Alzheimer's. Genetically predicted alcohol consumption, serum folate, serum vitamin B 12 , homocysteine, cardiometabolic factors, and C reactive protein were not associated with Alzheimer's disease. These results provide support that higher educational attainment is associated with a reduced risk of Alzheimer's disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Direct introduction of gene constructs into the pronucleus-like structure of cloned embryos: a new strategy for the generation of genetically modified pigs.

PubMed

Kurome, Mayuko; Leuchs, Simon; Kessler, Barbara; Kemter, Elisabeth; Jemiller, Eva-Maria; Foerster, Beatrix; Klymiuk, Nikolai; Zakhartchenko, Valeri; Wolf, Eckhard

2017-04-01

Due to a rising demand of porcine models with complex genetic modifications for biomedical research, the approaches for their generation need to be adapted. In this study we describe the direct introduction of a gene construct into the pronucleus (PN)-like structure of cloned embryos as a novel strategy for the generation of genetically modified pigs, termed "nuclear injection". To evaluate the reliability of this new strategy, the developmental ability of embryos in vitro and in vivo as well as the integration and expression efficiency of a transgene carrying green fluorescence protein (GFP) were examined. Eighty percent of the cloned pig embryos (633/787) exhibited a PN-like structure, which met the prerequisite to technically perform the new method. GFP fluorescence was observed in about half of the total blastocysts (21/40, 52.5%), which was comparable to classical zygote PN injection (28/41, 68.3%). In total, 478 cloned embryos injected with the GFP construct were transferred into 4 recipients and from one recipient 4 fetuses (day 68) were collected. In one of the fetuses which showed normal development, the integration of the transgene was confirmed by PCR in different tissues and organs from all three primary germ layers and placenta. The integration pattern of the transgene was mosaic (48 out of 84 single-cell colonies established from a kidney were positive for GFP DNA by PCR). Direct GFP fluorescence was observed macro- and microscopically in the fetus. Our novel strategy could be useful particularly for the generation of pigs with complex genetic modifications.

Reprint of "Fast and sensitive in vivo studies under controlled environmental conditions to substitute long-term field trials with genetically modified plants".

PubMed

Horn, Patricia; Schlichting, André; Baum, Christel; Hammesfahr, Ute; Thiele-Bruhn, Sören; Leinweber, Peter; Broer, Inge

2017-09-10

We introduce an easy, fast and effective method to analyze the influence of genetically modified (GM) plants on soil and model organisms in the laboratory to substitute laborious and time consuming field trials. For the studies described here we focused on two GM plants of the so-called 3rd generation: GM plants producing pharmaceuticals (PMP) and plant made industrials (PMI). Cyanophycin synthetase (cphA) was chosen as model for PMI and Choleratoxin B (CTB) as model for PMP. The model genes are expressed in transgenic roots of composite Vicia hirsuta plants grown in petri dishes for semi-sterile growth or small containers filled with non-sterile soil. No significant influence of the model gene expression on root induction, growth, biomass, interaction with symbionts such as rhizobia (number, size and functionality of nodules, selection of nodulating strains) or arbuscular mycorrhizal fungi could be detected. In vitro, but not in situ under field conditions, structural diversity of the bulk soil microbial community between transgenic and non-transgenic cultivars was determined by PLFA pattern-derived ratios of bacteria: fungi and of gram + : gram - bacteria. Significant differences in PLFA ratios were associated with dissimilarities in the quantity and molecular composition of rhizodeposits as revealed by Py-FIMS analyses. Contrary to field trials, where small effects based on the transgene expression might be hidden by the immense influence of various environmental factors, our in vitro system can detect even minor effects and correlates them to transgene expression with less space, time and labour. Copyright © 2016 Elsevier B.V. All rights reserved.

Correction of the lack of commutability between plasmid DNA and genomic DNA for quantification of genetically modified organisms using pBSTopas as a model.

PubMed

Zhang, Li; Wu, Yuhua; Wu, Gang; Cao, Yinglong; Lu, Changming

2014-10-01

Plasmid calibrators are increasingly applied for polymerase chain reaction (PCR) analysis of genetically modified organisms (GMOs). To evaluate the commutability between plasmid DNA (pDNA) and genomic DNA (gDNA) as calibrators, a plasmid molecule, pBSTopas, was constructed, harboring a Topas 19/2 event-specific sequence and a partial sequence of the rapeseed reference gene CruA. Assays of the pDNA showed similar limits of detection (five copies for Topas 19/2 and CruA) and quantification (40 copies for Topas 19/2 and 20 for CruA) as those for the gDNA. Comparisons of plasmid and genomic standard curves indicated that the slopes, intercepts, and PCR efficiency for pBSTopas were significantly different from CRM Topas 19/2 gDNA for quantitative analysis of GMOs. Three correction methods were used to calibrate the quantitative analysis of control samples using pDNA as calibrators: model a, or coefficient value a (Cva); model b, or coefficient value b (Cvb); and the novel model c or coefficient formula (Cf). Cva and Cvb gave similar estimated values for the control samples, and the quantitative bias of the low concentration sample exceeded the acceptable range within ±25% in two of the four repeats. Using Cfs to normalize the Ct values of test samples, the estimated values were very close to the reference values (bias -13.27 to 13.05%). In the validation of control samples, model c was more appropriate than Cva or Cvb. The application of Cf allowed pBSTopas to substitute for Topas 19/2 gDNA as a calibrator to accurately quantify the GMO.

Radiogenomics and radiotherapy response modeling

NASA Astrophysics Data System (ADS)

El Naqa, Issam; Kerns, Sarah L.; Coates, James; Luo, Yi; Speers, Corey; West, Catharine M. L.; Rosenstein, Barry S.; Ten Haken, Randall K.

2017-08-01

Advances in patient-specific information and biotechnology have contributed to a new era of computational medicine. Radiogenomics has emerged as a new field that investigates the role of genetics in treatment response to radiation therapy. Radiation oncology is currently attempting to embrace these recent advances and add to its rich history by maintaining its prominent role as a quantitative leader in oncologic response modeling. Here, we provide an overview of radiogenomics starting with genotyping, data aggregation, and application of different modeling approaches based on modifying traditional radiobiological methods or application of advanced machine learning techniques. We highlight the current status and potential for this new field to reshape the landscape of outcome modeling in radiotherapy and drive future advances in computational oncology.

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

Neutral null models for diversity in serial transfer evolution experiments.

PubMed

Harpak, Arbel; Sella, Guy

2014-09-01

Evolution experiments with microorganisms coupled with genome-wide sequencing now allow for the systematic study of population genetic processes under a wide range of conditions. In learning about these processes in natural, sexual populations, neutral models that describe the behavior of diversity and divergence summaries have played a pivotal role. It is therefore natural to ask whether neutral models, suitably modified, could be useful in the context of evolution experiments. Here, we introduce coalescent models for polymorphism and divergence under the most common experimental evolution assay, a serial transfer experiment. This relatively simple setting allows us to address several issues that could affect diversity patterns in evolution experiments, whether selection is operating or not: the transient behavior of neutral polymorphism in an experiment beginning from a single clone, the effects of randomness in the timing of cell division and noisiness in population size in the dilution stage. In our analyses and discussion, we emphasize the implications for experiments aimed at measuring diversity patterns and making inferences about population genetic processes based on these measurements. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Novel Phenotype Issues Raised in Cross-National Epidemiological Research on Drug Dependence

PubMed Central

Anthony, James C.

2010-01-01

Stage-transition models based on the American Diagnostic and Statistical Manual (DSM) generally are applied in epidemiology and genetics research on drug dependence syndromes associated with cannabis, cocaine, and other internationally regulated drugs (IRD). Difficulties with DSM stage-transition models have surfaced during cross-national research intended to provide a truly global perspective, such as the work of the World Mental Health Surveys (WMHS) Consortium. Alternative simpler dependence-related phenotypes are possible, including population-level count process models for steps early and before coalescence of clinical features into a coherent syndrome (e.g., zero-inflated Poisson regression). Selected findings are reviewed, based on ZIP modeling of alcohol, tobacco, and IRD count processes, with an illustration that may stimulate new research on genetic susceptibility traits. The annual National Surveys on Drug Use and Health can be readily modified for this purpose, along the lines of a truly anonymous research approach that can help make NSDUH-type cross-national epidemiological surveys more useful in the context of subsequent genome wide association (GWAS) research and post-GWAS investigations with a truly global health perspective. PMID:20201862

Habitat corridors facilitate genetic resilience irrespective of species dispersal abilities or population sizes.

PubMed

Christie, Mark R; Knowles, L Lacey

2015-06-01

Corridors are frequently proposed to connect patches of habitat that have become isolated due to human-mediated alterations to the landscape. While it is understood that corridors can facilitate dispersal between patches, it remains unknown whether corridors can mitigate the negative genetic effects for entire communities modified by habitat fragmentation. These negative genetic effects, which include reduced genetic diversity, limit the potential for populations to respond to selective agents such as disease epidemics and global climate change. We provide clear evidence from a forward-time, agent-based model (ABM) that corridors can facilitate genetic resilience in fragmented habitats across a broad range of species dispersal abilities and population sizes. Our results demonstrate that even modest increases in corridor width decreased the genetic differentiation between patches and increased the genetic diversity and effective population size within patches. Furthermore, we document a trade-off between corridor quality and corridor design whereby populations connected by high-quality habitat (i.e., low corridor mortality) are more resilient to suboptimal corridor design (e.g., long and narrow corridors). The ABM also revealed that species interactions can play a greater role than corridor design in shaping the genetic responses of populations to corridors. These results demonstrate how corridors can provide long-term conservation benefits that extend beyond targeted taxa and scale up to entire communities irrespective of species dispersal abilities or population sizes.

Habitat corridors facilitate genetic resilience irrespective of species dispersal abilities or population sizes

PubMed Central

Christie, Mark R; Knowles, L Lacey

2015-01-01

Corridors are frequently proposed to connect patches of habitat that have become isolated due to human-mediated alterations to the landscape. While it is understood that corridors can facilitate dispersal between patches, it remains unknown whether corridors can mitigate the negative genetic effects for entire communities modified by habitat fragmentation. These negative genetic effects, which include reduced genetic diversity, limit the potential for populations to respond to selective agents such as disease epidemics and global climate change. We provide clear evidence from a forward-time, agent-based model (ABM) that corridors can facilitate genetic resilience in fragmented habitats across a broad range of species dispersal abilities and population sizes. Our results demonstrate that even modest increases in corridor width decreased the genetic differentiation between patches and increased the genetic diversity and effective population size within patches. Furthermore, we document a trade-off between corridor quality and corridor design whereby populations connected by high-quality habitat (i.e., low corridor mortality) are more resilient to suboptimal corridor design (e.g., long and narrow corridors). The ABM also revealed that species interactions can play a greater role than corridor design in shaping the genetic responses of populations to corridors. These results demonstrate how corridors can provide long-term conservation benefits that extend beyond targeted taxa and scale up to entire communities irrespective of species dispersal abilities or population sizes. PMID:26029259

Biocontainment of genetically modified organisms by synthetic protein design

PubMed Central

Mandell, Daniel J.; Lajoie, Marc J.; Mee, Michael T.; Takeuchi, Ryo; Kuznetsov, Gleb; Norville, Julie E.; Gregg, Christopher J.; Stoddard, Barry L.; Church, George M.

2015-01-01

Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient either because they impose evolutionary pressure on the organism to eject the safeguard, because they can be circumvented by environmentally available compounds, or because they can be overcome by horizontal gene transfer (HGT). Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code to confer metabolic dependence on nonstandard amino acids for survival. The resulting GMOs cannot metabolically circumvent their biocontainment mechanisms using environmentally available compounds, and they exhibit unprecedented resistance to evolutionary escape via mutagenesis and HGT. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by reliance on synthetic metabolites. PMID:25607366

The Influence of Genetics on Cystic Fibrosis Phenotypes

PubMed Central

Knowles, Michael R.; Drumm, Mitchell

2012-01-01

Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF. PMID:23209180

The Detection of Genetically Modified Organisms: An Overview

NASA Astrophysics Data System (ADS)

Ovesná, Jaroslava; Demnerová, Kateřina; Pouchová, Vladimíra

Genetically modified organisms (GMOs) are those whose genetic material has been altered by the insertion of a new gene or by the deletion of an existing one(s). Modern biotechnology, in particular, the rise of genetic engineering, has supported the development of GMOs suitable for research purposes and practical applications (Gepts, 2002; Novoselova,Meuwissen, & Huirne, 2007; Sakakibara & Saito, 2006). For over 20 years GM bacteria and other GM organisms have been used in laboratories for the study of gene functions (Maliga & Small, 2007; Ratledge & Kristiansen, 2006). Agricultural plants were the first GMOs to be released into the environment and placed on the market. Farmers around the world use GMsoybeans, GMcorn and GM cotton that are herbicide tolerant, or insect resistant, or combine several traits that reduce the costs associated with crop production (Corinne, Fernandez-Cornejo, & Goodhue, 2004).

Biocontainment of genetically modified organisms by synthetic protein design.

PubMed

Mandell, Daniel J; Lajoie, Marc J; Mee, Michael T; Takeuchi, Ryo; Kuznetsov, Gleb; Norville, Julie E; Gregg, Christopher J; Stoddard, Barry L; Church, George M

2015-02-05

Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient because they impose evolutionary pressure on the organism to eject the safeguard by spontaneous mutagenesis or horizontal gene transfer, or because they can be circumvented by environmentally available compounds. Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code (Escherichia coli strain C321.ΔA) to confer metabolic dependence on non-standard amino acids for survival. The resulting GMOs cannot metabolically bypass their biocontainment mechanisms using known environmental compounds, and they exhibit unprecedented resistance to evolutionary escape through mutagenesis and horizontal gene transfer. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites.

Biocontainment of genetically modified organisms by synthetic protein design

NASA Astrophysics Data System (ADS)

Mandell, Daniel J.; Lajoie, Marc J.; Mee, Michael T.; Takeuchi, Ryo; Kuznetsov, Gleb; Norville, Julie E.; Gregg, Christopher J.; Stoddard, Barry L.; Church, George M.

2015-02-01

Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient because they impose evolutionary pressure on the organism to eject the safeguard by spontaneous mutagenesis or horizontal gene transfer, or because they can be circumvented by environmentally available compounds. Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code (Escherichia coli strain C321.ΔA) to confer metabolic dependence on non-standard amino acids for survival. The resulting GMOs cannot metabolically bypass their biocontainment mechanisms using known environmental compounds, and they exhibit unprecedented resistance to evolutionary escape through mutagenesis and horizontal gene transfer. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites.

Genetic and epigenetic control of gene expression by CRISPR–Cas systems

PubMed Central

Lo, Albert; Qi, Lei

2017-01-01

The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems has revolutionized the way researchers edit genomes. Engineering of catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas]) combined with transcriptional repressors, activators, or epigenetic modifiers enable sequence-specific regulation of gene expression and chromatin state. These CRISPR–Cas-based technologies have contributed to the rapid development of disease models and functional genomics screening approaches, which can facilitate genetic target identification and drug discovery. In this short review, we will cover recent advances of CRISPR–dCas9 systems and their use for transcriptional repression and activation, epigenome editing, and engineered synthetic circuits for complex control of the mammalian genome. PMID:28649363

Genetic engineering of industrial Saccharomyces cerevisiae strains using a selection/counter-selection approach.

PubMed

Kutyna, Dariusz R; Cordente, Antonio G; Varela, Cristian

2014-01-01

Gene modification of laboratory yeast strains is currently a very straightforward task thanks to the availability of the entire yeast genome sequence and the high frequency with which yeast can incorporate exogenous DNA into its genome. Unfortunately, laboratory strains do not perform well in industrial settings, indicating the need for strategies to modify industrial strains to enable strain development for industrial applications. Here we describe approaches we have used to genetically modify industrial strains used in winemaking.

Plant biotechnology in China.

PubMed

Huang, Jikun; Rozelle, Scott; Pray, Carl; Wang, Qinfang

2002-01-25

A survey of China's plant biotechnologists shows that China is developing the largest plant biotechnology capacity outside of North America. The list of genetically modified plant technologies in trials, including rice, wheat, potatoes, and peanuts, is impressive and differs from those being worked on in other countries. Poor farmers in China are cultivating more area of genetically modified plants than are small farmers in any other developing country. A survey of agricultural producers in China demonstrates that Bacillus thuringiensis cotton adoption increases production efficiency and improves farmer health.

African Security Challenges: Now and Over the Horizon. Food Security and Conflict: Current and Future Dimensions of the Challenge in Africa

DTIC Science & Technology

2010-04-01

that area. Violence over Genetically-Modified Organisms ( GMOs ) While the experts agreed that there were not many, if any, major cases of...violent outbreaks over genetically-modified organism ( GMOs ) issues in Africa, there was some agreement that under certain circumstances, when combined...with other issues, these could be a trigger for riots and other forms of violent political protest. However, GMO issues should not be viewed as a

Evaluation of biotechnology-derived novel proteins for the risk of food-allergic potential: advances in the development of animal models and future challenges.

PubMed

Ahuja, Varun; Quatchadze, Maria; Ahuja, Vaishali; Stelter, Daniela; Albrecht, Achim; Stahlmann, Ralf

2010-12-01

Increasing concern from the public about the safety of genetically modified food has made critical to have suitable methods for recognizing associated potential hazards. Hierarchical approaches to allergenicity determination were proposed, and these include evaluation of the structural and sequence homology and serological identity of novel proteins with existing allergens, measuring the resistance to proteolytic digestion and assessment of sensitizing potential using animal models. Allergic individuals have a predisposed (i.e. atopic) genetic background, and a close resemblance to this setup is therefore desirable in animal models, which is possible by using a strain of an animal species that is prone for allergic disorders. So far, none of the animal model has been validated for the purpose of hazard identification in the context of safety assessment. However, the available knowledge suggests that the judicious use of an appropriate animal model could provide important information about the allergic potential of novel proteins. This paper provides an up-to-date review of the progress made in the field of development of in vivo models in this direction and the further goals that have to be achieved.

Genetic modifiers of abnormal organelle biogenesis in a Drosophila model of BLOC-1 deficiency

PubMed Central

Cheli, Verónica T.; Daniels, Richard W.; Godoy, Ruth; Hoyle, Diego J.; Kandachar, Vasundhara; Starcevic, Marta; Martinez-Agosto, Julian A.; Poole, Stephen; DiAntonio, Aaron; Lloyd, Vett K.; Chang, Henry C.; Krantz, David E.; Dell'Angelica, Esteban C.

2010-01-01

Biogenesis of lysosome-related organelles complex 1 (BLOC-1) is a protein complex formed by the products of eight distinct genes. Loss-of-function mutations in two of these genes, DTNBP1 and BLOC1S3, cause Hermansky–Pudlak syndrome, a human disorder characterized by defective biogenesis of lysosome-related organelles. In addition, haplotype variants within the same two genes have been postulated to increase the risk of developing schizophrenia. However, the molecular function of BLOC-1 remains unknown. Here, we have generated a fly model of BLOC-1 deficiency. Mutant flies lacking the conserved Blos1 subunit displayed eye pigmentation defects due to abnormal pigment granules, which are lysosome-related organelles, as well as abnormal glutamatergic transmission and behavior. Epistatic analyses revealed that BLOC-1 function in pigment granule biogenesis requires the activities of BLOC-2 and a putative Rab guanine-nucleotide-exchange factor named Claret. The eye pigmentation phenotype was modified by misexpression of proteins involved in intracellular protein trafficking; in particular, the phenotype was partially ameliorated by Rab11 and strongly enhanced by the clathrin-disassembly factor, Auxilin. These observations validate Drosophila melanogaster as a powerful model for the study of BLOC-1 function and its interactions with modifier genes. PMID:20015953

Chaotic dynamics and diffusion in a piecewise linear equation

NASA Astrophysics Data System (ADS)

Shahrear, Pabel; Glass, Leon; Edwards, Rod

2015-03-01

Genetic interactions are often modeled by logical networks in which time is discrete and all gene activity states update simultaneously. However, there is no synchronizing clock in organisms. An alternative model assumes that the logical network is preserved and plays a key role in driving the dynamics in piecewise nonlinear differential equations. We examine dynamics in a particular 4-dimensional equation of this class. In the equation, two of the variables form a negative feedback loop that drives a second negative feedback loop. By modifying the original equations by eliminating exponential decay, we generate a modified system that is amenable to detailed analysis. In the modified system, we can determine in detail the Poincaré (return) map on a cross section to the flow. By analyzing the eigenvalues of the map for the different trajectories, we are able to show that except for a set of measure 0, the flow must necessarily have an eigenvalue greater than 1 and hence there is sensitive dependence on initial conditions. Further, there is an irregular oscillation whose amplitude is described by a diffusive process that is well-modeled by the Irwin-Hall distribution. There is a large class of other piecewise-linear networks that might be analyzed using similar methods. The analysis gives insight into possible origins of chaotic dynamics in periodically forced dynamical systems.

The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model.

PubMed

Mirzaei, Hamed; Salehi, Hossein; Oskuee, Reza Kazemi; Mohammadpour, Ali; Mirzaei, Hamid Reza; Sharifi, Mohammad Reza; Salarinia, Reza; Darani, Hossein Yousofi; Mokhtari, Mojgan; Masoudifar, Aria; Sahebkar, Amirhossein; Salehi, Rasoul; Jaafari, Mahmoud Reza

2018-04-10

Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

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

Guseva, Daria; Hannover Medical School, Hannover; Rizvanov, Albert A.

2014-09-05

Highlights: • Gene and cell-based therapies comprise innovative aspects of regenerative medicine. • Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS. • Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords. • Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5. • Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. - Abstract: Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignantmore » transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis.« less