Academic literature on the topic 'Non genomic effects'
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Journal articles on the topic "Non genomic effects"
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Verhovez, Andrea, Tracy A. Williams, Silvia Monticone, Valentina Crudo, Jacopo Burrello, Maddalena Galmozzi, Michele Covella, Franco Veglio, and Paolo Mulatero. "Genomic and Non-genomic Effects of Aldosterone." Current Signal Transduction Therapy 7, no. 2 (May 1, 2012): 132–41. http://dx.doi.org/10.2174/157436212800376708.
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Kowalik, M. K., D. Slonina, and J. Kotwica. "Genomic and non-genomic effects of progesterone and pregnenolone on the function of bovine endometrial cells." Veterinární Medicína 54, No. 5 (June 1, 2009): 205–14. http://dx.doi.org/10.17221/58/2009-vetmed.
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Progesterone (P<sub4</sub>) decreases oxytocin (OT)-stimulated prostaglandin (PG)F<sub>2α</sub>, but not PGE<sub>2</sub> secretion from bovine endometrial cells and this effect is partly elicited via a non-genomic route. The aim of this study was to determine whether P<sub>4</sub> and pregnenolone (P<sub>5</sub>), in the presence or absence of OT, influence: (a) the gene expression of enzymes responsible for PG<sub>s</sub> synthesis: cyclooxygenase-2 (COX-2), synthase of PGF<sub>2α</sub> (PGFS) and PGE=sub>2</sub> (PGES), (b) protein expression of COX-2, PGFS and PGES, and (c) P<sub>4</sub> receptor membrane component 1 (PGRMC1) gene expression in bovine endometrial cells. The epithelial endometrial cells (2.5 × 10<sup>5</sup>/ml) from Days 14–16 of the oestrous cycle were incubated for 72–96 h to attach the cells to the bottom of a well. Next, the cells were preincubated for 30 min with P<sub>4</sub> and P<sub>5</sub> (10<sup>–5</sup>M each) and incubated for 4 h and 6 h alone or with OT (10<sup>–7</sup>M). Thereafter, the medium was collected for PGE<sub>2</sub> and PGFM determination, while cells were harvested for gene and protein expression analysis. The used steroids: (a) inhibited OT-stimulated PGF<sub>2α</sub>, but not PGE<sub>2</sub> secretion from endometrial cells, (b) did not affect the expression of mRNA for COX-2, PGFS, PGES and PGRMC1 in endometrial cells after 4 and 6 h, (c) they decreased OT-stimulated COX-2 mRNA expression only after 6 h incubation, and (d) did not influence COX-2, PGFS and PGES protein expression after 6 h. These results indicate that P<sub>4</sub> and P<sub>5</sub> inhibit OT-stimulated secretion/production of luteolytic PGF<sub>2α</sub> by a transcription-independent mechanism and partly by down-regulation of COX-2 mRNA.
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Ordóñez-Morán, Paloma, and Alberto Muñoz. "Nuclear receptors: Genomic and non-genomic effects converge." Cell Cycle 8, no. 11 (June 2009): 1675–80. http://dx.doi.org/10.4161/cc.8.11.8579.
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Viñas, René, Yow-Jiun Jeng, and Cheryl S. Watson. "Non-Genomic Effects of Xenoestrogen Mixtures." International Journal of Environmental Research and Public Health 9, no. 8 (July 31, 2012): 2694–714. http://dx.doi.org/10.3390/ijerph9082694.
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Jia, Wan-Yu, and Jian-Jiang Zhang. "Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms." World Journal of Clinical Cases 10, no. 21 (July 26, 2022): 7187–94. http://dx.doi.org/10.12998/wjcc.v10.i21.7187.
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McEwen, Bruce S. "Non-genomic and genomic effects of steroids on neural activity." Trends in Pharmacological Sciences 12 (January 1991): 141–47. http://dx.doi.org/10.1016/0165-6147(91)90531-v.
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Weiss, Daniel J., and Erlio Gurpide. "Non-genomic effects of estrogens and antiestrogens." Journal of Steroid Biochemistry 31, no. 4 (October 1988): 671–76. http://dx.doi.org/10.1016/0022-4731(88)90017-9.
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SIMONCINI, T. "Genomic and non-genomic effects of estrogens on endothelial cells*1." Steroids 69, no. 8-9 (August 2004): 537–42. http://dx.doi.org/10.1016/j.steroids.2004.05.009.
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Lecoq, L., P. Vincent, A. Lavoie-Lamoureux, and J. P. Lavoie. "Genomic and non-genomic effects of dexamethasone on equine peripheral blood neutrophils." Veterinary Immunology and Immunopathology 128, no. 1-3 (March 2009): 126–31. http://dx.doi.org/10.1016/j.vetimm.2008.10.303.
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Bruscoli, Stefano, Rosa Di Virgilio, Valerio Donato, Enrico Velardi, Monia Baldoni, Cristina Marchetti, Graziella Migliorati, and Carlo Riccardi. "Genomic and non-genomic effects of different glucocorticoids on mouse thymocyte apoptosis." European Journal of Pharmacology 529, no. 1-3 (January 2006): 63–70. http://dx.doi.org/10.1016/j.ejphar.2005.10.053.
Full textDissertations / Theses on the topic "Non genomic effects"
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Guarino, Goffredo <1979>. "Genomic and non genomic effects of elevated concentration of anabolic steroids in human neuronal cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/693/1/Tesi_Guarino_Goffredo.pdf.
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Nandrolone and other anabolic androgenic steroids (AAS) at elevated concentration can alter
the expression and function of neurotransmitter systems and contribute to neuronal cell death.
This effect can explain the behavioural changes, drug dependence and neuro degeneration
observed in steroid abuser.
Nandrolone treatment (10-8M–10-5M) caused a time- and concentration-dependent
downregulation of mu opioid receptor (MOPr) transcripts in SH-SY5Y human neuroblastoma
cells. This effect was prevented by the androgen receptor (AR) antagonist hydroxyflutamide.
Receptor binding assays confirmed a decrease in MOPr of approximately 40% in nandrolonetreated
cells. Treatment with actinomycin D (10-5M), a transcription inhibitor, revealed that
nandrolone may regulate MOPr mRNA stability. In SH-SY5Y cells transfected with a human
MOPr luciferase promoter/reporter construct, nandrolone did not alter the rate of gene
transcription. These results suggest that nandrolone may regulate MOPr expression through
post-transcriptional mechanisms requiring the AR.
Cito-toxicity assays demonstrated a time- and concentration dependent decrease of
cells viability in SH-SY5Y cells exposed to steroids (10-6M–10-4M). This toxic effects is
independent of activation of AR and sigma-2 receptor. An increased of caspase-3 activity was
observed in cells treated with Nandrolone 10-6M for 48h.
Collectively, these data support the existence of two cellular mechanisms that might
explain the neurological syndromes observed in steroids abuser.
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Guarino, Goffredo <1979>. "Genomic and non genomic effects of elevated concentration of anabolic steroids in human neuronal cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/693/.
Full textAbstract:
Nandrolone and other anabolic androgenic steroids (AAS) at elevated concentration can alter
the expression and function of neurotransmitter systems and contribute to neuronal cell death.
This effect can explain the behavioural changes, drug dependence and neuro degeneration
observed in steroid abuser.
Nandrolone treatment (10-8M–10-5M) caused a time- and concentration-dependent
downregulation of mu opioid receptor (MOPr) transcripts in SH-SY5Y human neuroblastoma
cells. This effect was prevented by the androgen receptor (AR) antagonist hydroxyflutamide.
Receptor binding assays confirmed a decrease in MOPr of approximately 40% in nandrolonetreated
cells. Treatment with actinomycin D (10-5M), a transcription inhibitor, revealed that
nandrolone may regulate MOPr mRNA stability. In SH-SY5Y cells transfected with a human
MOPr luciferase promoter/reporter construct, nandrolone did not alter the rate of gene
transcription. These results suggest that nandrolone may regulate MOPr expression through
post-transcriptional mechanisms requiring the AR.
Cito-toxicity assays demonstrated a time- and concentration dependent decrease of
cells viability in SH-SY5Y cells exposed to steroids (10-6M–10-4M). This toxic effects is
independent of activation of AR and sigma-2 receptor. An increased of caspase-3 activity was
observed in cells treated with Nandrolone 10-6M for 48h.
Collectively, these data support the existence of two cellular mechanisms that might
explain the neurological syndromes observed in steroids abuser.
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Li, Xiongjuan [Verfasser]. "Genomic and non-genomic effects of mineralocorticoid receptors and glucocorticoid receptors and their roles of pain modulation / Xiongjuan Li." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1196803218/34.
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LA, SALA GINA. "Effetti degli estrogeni e dei distruttori endocrini sulle cellule germinali embrionali di topo e sulle cellule somatiche della gonade." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/901.
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Negli ultimi anni si è assistito ad un crescente aumento nell’ambiente di sostanze che sono in grado di alterare il sistema endocrino poiché agiscono come l’ormone naturale estrogeno e per questo definite distruttori endocrini (EDs). Si ipotizza che l’esposizione agli EDs durante il periodo fetale e neo-natale sia la causa dell’insorgenza di numerosi disordini dell’apparato riproduttivo maschile come sterilità, cancro del testicolo, criptorchidismo e ipospadia che vengono definite con il termine unico di sindrome del testicolo disgenico (TDS). E’ importante studiare gli effetti degli estrogeni e degli xenoestrogeni, una classe di EDs, durante il periodo fetale ed in particolare durante lo sviluppo dell’apparto riproduttivo e conoscere i meccanismi, con cui tali sostanze esplicano i loro effetti.
OBIETTIVI. Verificare l'espressione dei recettori degli estrogeni (ERs) nei precursori dei gameti adulti, ovvero nelle cellule germinali di topo denominate PGCs e analizzare i pathways molecolari attivati in queste cellule dagli estrogeni e dallo xenoestrogeno lindano. Inoltre si vuole verificare la presenza di ERs funzionali nelle cellule somatiche testicolari embrionali utilizzando costrutti ERE-luc e AP1-Luc per valutare l'attività estrogenica di xenoestrogeni.
RISULTATI. Lo studio condotto in questa tesi mette in evidenza l'esistenza di pathways molecolari attivabili dall’estrogeno (E2) nelle gonadi embrionali di topo, in particolare, nel testicolo, sia nelle cellule germinali primordiali che nelle cellule somatiche. Abbiamo osservato che l’E2 è in grado di attivare, attraverso il recettore degli estrogeni ERα , importanti chinasi nelle PGCs (AKT, ERK1/2 e SRC) con effetti positivi sulla crescita e proliferazione di tali cellule. Si è osservato che il lindano, al contrario dell’E2, influenza negativamente la sopravvivenza di tali cellule attraverso una azione pro-apoptotica diretta, probabilmente derivante da effetti negativi sull’attività chinasica AKT. Inoltre abbiamo descritto per la prima volta l'esistenza di un recettore dell’estrogeno funzionale nelle cellule del Leydig testicolari durante lo stadio precoce dello sviluppo e messo a punto un test in vitro che può essere utilizzato per valutare l'attività estrogenica di xenoestrogeni direttamente sulle cellule del testicolo embrionale di mammiferi.
CONCLUSIONI: Questi risultati rafforzano l’ipotesi dell’origine fetale della TDS. Numerosi studi hanno messo in evidenza gli effetti diretti degli estrogeni sul sistema endocrino, sull'espressione genica e su funzioni specifiche delle cellule somatiche testicolari embrionali, in particolare sulle cellule del Leydig, tuttavia tali studi sono carenti nelle cellule germinali. E’ importante conoscere i meccanismi di azione degli xenoestrogeni sullePGCs visto che attraverso esse viene trasmesso il genoma alle generazioni successive.In the recent years the increased presence of human made compounds that mimic the action of estrogens termed endocrine disrupters (ED) in environment and in food and the exposure to these compounds during fetal and neonatal period has been hypotized to be the cause of the raise of disorders of male reproductive function, such a decrease of sperm count, increase in the incidence of testicular cancer and cryptorchidism and hypospadias termed Testicular Dysgenesis Syndrome (TDS). For these reason, it is important to know how the estrogens and xenoestrogens, a class of ED, act during the fetal development and to know the mechanism by which these compounds exert their effects. AIMS: To study the expression of estrogen receptors (ERs) in the embryonic precursors of the adult gametes termed PGCs and to analyze the existence in such cells of intracellular molecular pathways modulable by estrogens and xenoestrogen lindane. To verify the presence of functional ER-beta in embryonic testicular somatic cells using an ERE-luc and AP1-Luc assay and to evaluate estrogenic activity of putative EDs on mammalian embryonic testis. RESULTS: The data described in this thesis highlights the existence of functional estrogen-dependent pathways in embryonic mouse gonads in particular in testis, both in germ and somatic cells. We found that E2 is able to activate via ER-beta multiple intracellular signalling in PGCs and that the xenoestrogens, lindane affect the survival in such cells through a direct pro-apoptotic action likely resulting from its adverse effect on AKT activity. Othermore, we described for the first time the existence of a functional ERα pathway in putative Leydig cells from early stage of testis development and describe an in vitro assay that can be used to evaluate estrogenic activity of compounds on mammalian embryonic testis. CONCLUSIONS: These results support the notion of the TDS origin during early stages of testis development. While data are accumulating showing direct effect of estrogens and EDs on gene expression and specific functions of somatic cells of the embryonic testes, in particular Leydig cells, such results on germ cells are lacking and further studies are needed to investigate the effects of these compounds on embryonic germ cell function including epigenetic regulation.
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Gonzalez, Dieguez David. "Genomic selection accounting for non-additive genetic effects in pig and corn crossbreeding schemes." Thesis, Toulouse, INPT, 2020. http://www.theses.fr/2020INPT0078.
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Cette thèse explore et développe des méthodes pour exploiter les effets génétiques de dominance ou/et d'épistasie sur des modèles de sélection génomique dans les schémas de sélection utilisant le croisement chez le porc et le maïs. Le Chapitre 2 a consisté à estimer et à exploiter la variance de dominance intra-race à travers des stratégies de planification des accouplements pour maximiser le progrès génétique global de l’âge à 100 kg (AGE), de l’épaisseur de lard dorsal (BD) et du poids moyen des porcelets par portée (APWL), dans une population porcine de race Landrace française. La maximisation de la valeur génétique totale au lieu de la seule partie additive dans la planification des accouplements a donné à la descendance un avantage moyen de -0,79 jour, -0,04 mm et 11,3 g pour AGE, BD et APWL, respectivement. En contrepartie, le gain génétique additif attendu a légèrement été réduit (1,8% pour AGE par exemple). Ces résultats indiquent que la planification des accouplements peut améliorer les performances des descendants sans compromettre considérablement le progrès génétique. Dans le Chapitre 3, l'efficacité de la planification des accouplements et de l’évaluation génomique, en tenant compte des effets additifs et de dominance, pour améliorer les performances des individus croisés (CB) a été étudiée par simulation dans un croisement à deux voies chez le porc. Les effets de l’utilisation de différentes sources d'informations dans l'évaluation génétique (uniquement des données de race pure (PB) ou des données PB et CB), de plusieurs valeurs d'héritabilité au sens étroit et large, et de plusieurs stratégies d’accouplement pour produire les animaux CB (accouplements au hasard, minimisant la consanguinité future ou maximisant la valeur génétique totale attendue des animaux CB) ont été évaluées. La sélection des animaux PB sur leurs performances en PB a donné un gain génétique de 0,2 écart-type génétique par génération pour le caractère « performance en croisement ». Ce gain a été doublé lorsque les animaux PB étaient sélectionnés sur leur performance en croisés. Les stratégies d’accouplement a entraîné une légère augmentation des performances des animaux CB. Lorsque la corrélation génétique entre les performances exprimées chez les animaux PB et CB est faible, la sélection des animaux PB pour leur performance en croisés en utilisant les informations CB est une stratégie plus efficace pour exploiter l'hétérosis et augmenter les performances des animaux CB au niveau commercial. Dans le Chapitre 4, la théorie des modèles d'évaluation génétique chez des hybrides à partir du croisement de lignées pures (comme pour le maïs) a été revue dans un contexte génomique. La covariance entre les hybrides due aux effets de substitution additifs, à la dominance et à l’épistasie a été dérivée analytiquement. En utilisant les marqueurs SNP, il est possible de décomposer l’aptitude spécifique à la combinaison (SCA) en dominance et épistasie intergroupes, et de décomposer les aptitudes générales à la combinaison (GCA) en effets additifs intra-lignée et une épistasie additive par additive intra-ligne. Un jeu de données publiques sur des hybrides Dent × Flint a été analysé. Le modèle proposé a été comparé à d'autres modèles génomiques en termes d'estimations des composantes de variance et de capacité prédictive, y compris un modèle supposant un effet commun des gènes des lignées pures. L'étude confirme que la majeure partie de la variabilité observée chez les hybrides est expliquée par la GCA et que les variances dues à la dominance et à l'épistasie sont moins importants et du même ordre de grandeur. Les modèles basés sur la définition d’effets différents (comme traditionnellement considérés chez le maïs), ou commun aux origines (comme considérés intra-race en sélection animale) ont abouti à des capacités prédictives similaires pour les hybridesThis thesis explores and develops methodology to exploit dominance or/and epistasis genetic effects on genomic selection models in pig and maize crossbreeding schemes. The Chapter 2 consisted of estimating and exploiting within-breed dominance variance through mate allocation strategies to maximize the overall genetic merit of the traits age at 100 Kg (AGE), backfat depth (BD) and average piglet weight per litter (APWL), in a French Landrace pig population. Maximizing total genetic values instead of breeding values in matings gave to the progeny an average advantage of 0.79 days, 0.04 mm, and 11.3 g for AGE, BD and APWL, respectively, but slightly reduced the expected additive genetic gain (e.g. 1.8 % for AGE). These results indicate that genomic mate allocation can improve the performance of the offspring without dramatically compromising the additive genetic gain. In Chapter 3, the effectiveness of mate allocation strategies and genomic evaluations, accounting for additive and dominance effects, to improve crossbred (CB) performance were investigated by simulation in a two-way pig crossbreeding scheme. Effects of the sources of information used in the genetic evaluation (only purebred (PB) data or PB and CB data), of several narrow and broad-sense heritability values, and of several options for mate allocation to produce the CB (mating at random, minimizing expected future inbreeding, or maximizing the expected total genetic value of crossbred animals) were evaluated. Selecting PB animals for PB performance yielded a genetic gain of 0.2 genetic standard deviations of the trait “CB performance” per generation, whereas selecting PB animals for CB performance doubled the genetic response. Mate allocation strategy resulted in a slight increase of the CB performance. When the genetic correlation between PB and CB is low, selecting PB animals for CB performance using CB information is a more efficient strategy to exploit heterosis and increase performance at the CB commercial level. In Chapter 4, the theory of hybrid genetic evaluation models from single-cross of pure lines (as in maize) was revisited in a genomic context. Covariance between hybrids due to additive substitution effects and dominance and epistatic deviations were analytically derived. Using SNP genotypes, it is possible to split specific combining ability (SCA) into dominance and across-groups epistasis, and to split general combining ability (GCA) into within-line additive effects and within-line additive by additive epistasis. A publicly available maize data set of Dent × Flint hybrids was analyzed. The proposed model was compared to other genomic models in terms of variance components estimation and predictive ability, including a model assuming a common effect of genes across origins. The study confirms that most variation in hybrids is accounted for by GCA, and that variances due to dominance and epistasis are small and have similar magnitudes. Models based on defining effects either differently (as it is traditionally done in maize) or identically across origins (as it is done in single breeds in livestock) resulted in similar predictive abilities for hybrids
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Strelzyk, Florian [Verfasser]. "Rapid, non-genomic effects of cortisol on the functioning of the human brain / Florian Strelzyk." Trier : Universität Trier, 2011. http://d-nb.info/1197697721/34.
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Almeida, Filho Janeo Eustáquio de. "Genomic prediction of additive and non-additive effects in a pine breeding and simulated population." Universidade Federal de Viçosa, 2016. http://www.locus.ufv.br/handle/123456789/7540.
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A predição do mérito genético dos indivíduos é um dos maiores desafios no melhoremento de plantas e animais. A predição é difícil por que as características importantes possuem natureza complexa, onde alguns caracteres possuem poucos genes de efeito maior, enquanto que outros são controlados por um elevado número de genes de efeito pequeno, além disso, efeitos não-additivos como dominância e epistasia podem ser importantes para o controle da variação genética. Para obter altas acurácias na predição é importante usar o modelo que corresponde com a arquitetura genética da característica e adicionalmente a adequada partição das várias fontes de variação genética (aditiva, dominancia e epistasia) é desejada para várias aplicações como capacidade geral e específica de combinação. No capítulo 1 foi revisado os aspectos gerais da predição genômica (GP), a aplicação dessa abordagem com diferentes propósitos em características com distintas arquiteturas genéticas e no final alguns modelos estatísticos aplicado na GP. No capítulo 2 foi avaliado modelos de regressão genômica (WGR) aditivos e aditivo-dominante com diferentes prioris, essas são premissas sobre a presença ou não de marcas com efeito maior. Adicionalmente no capítulo 3 foi avaliado a inclusão da informação oriunda do pedigree na predição genômica, usando os modelos BayesA aditivo e aditivo-dominante e também com o RKHS, que teoricamente pode predizer os efeitos aditivo e não aditivos confundidos. Esses modelos foram aplicados na altura de árvores (HT) aos 6 anos de idade, diâmetro na altura do peito (DBH) e resistência a ferrugem, mesurados em 923 indivíduos de pinos oriundos de uma população estruturada em 71 irmãos completos e genotipados com 4722 marcadores genéticos. Também foram simulados 6 características com distintas arquiteturas genéticas (poligenica e oligogênica com três leveis de dominância) para esses estudos. As populações simuladas usadas nessas características foram derivadas a partir de um programa de melhoramento padrão de pinos. No capítulo 2 para as caracteríticas oligogenica simuladas e para resistência a ferrugem o BayesA e BayesB forneceram as melhores acurácias para predição genotípica, porem as diferentes priores usadas em WGR produziram resultados similares para HT e para característica poligênicas simuladas. Contudo a inclusão da dominância nos modelos WGR aumentaram a acurácia apenas para características simuladas com elevado efeito de dominância e para HT. Quando o BayesB foi ajustado em uma geração para predizer na geração seguinte, a inclusão da dominância aumentou as acurácias apenas para características oligogenicas simuladas com elevada dominancia. Independente do modelo adotado, a acurácia da predição genotípica total decresceu com o aumento dos efeitos de dominancia nas características simuladas. Então esses resultados refletem que a predição da dominancia foi complexa quando comparado com a predição dos efeitos aditivos, e para a aplicações posteriores dos efeitos de dominância, algumas propriedades genéticas da população devem ser avaliadas como MAF e número de meios irmãos e irmãos completos. No capítulo 3, a inclusão do informação oriunda do pedigree no modelo genômico, não produziu acurácias mais elevadas quando comparado com os modelos que usaram apenas informações de marcadores, e ambos modelos foram substancialmente mais acurados que o modelo baseado apenas em informação de pedigree. Em HT, DBH e características poligênicas simuladas com efeitos aditivos e dominantes, os modelos baseados em RKHS mostraram acurácias ligeiramente superiores que o BayesA para predição genotípica total, enquanto que o BayesA foi a melhor opção para resistência a ferrugem e características oligogenicas. Para a predição dos valores de melhoramento o BayesA aditivo foi o melhor modelo.
The prediction of individual genetic merit is one of most important challenges in plant and animal breeding. Prediction is difficult because the important traits have a complex nature, where some traits have few genes with major effects, while others are controlled by a large number of genes with small effects. Non-additive effects such as dominance and epistasis can also be important for controlling the genetic variation. In order to achieve higher accuracies in the prediction, it is important to use the model that matches the genetic architecture of trait. The proper partition of the various sources of genetic variation (additive, dominance and epistasis) is desired for several applications, such as exploring the overall and specific combination ability. In Chapter 1, the general remarks of genomic prediction (GP) are reviewed, with the application of this approach with different proposals in distinct genetic architecture traits, together with some statistic models applied in GP. In Chapter 2, the additive and additive-dominance whole-genomic-regression (WGR) models are evaluated with different priors, together with assumptions regarding the presence or not of markers with major effects. Chapter 3 evaluates the inclusion of pedigree information in genomic prediction with additive- and additive-dominance BayesA and also with RKHS model that can theoretically predict confused additive and non- additive effects. These models were applied in tree height (HT), diameter at breast height (DBH) and rust resistance in 923 loblolly pine individuals at 6 years of age from a structured population of 71 full-sib families genotyped with 4722 genetic markers. Six traits were also simulated with distinct genetic architectures (polygenic and oligogenic traits with three dominance levels) for these studies. The simulated population for these traits was derived from a standard pine breeding program. In the oligogenic simulated traits and rust resistance in chapter 2, BayesA and BayesB provided greater accuracies for genotypic prediction; however, the different priors of WGR yielded similar results for HT and simulated polygenic traits. Therefore, the inclusion of dominance effects in WGR increases the accuracy only for simulated traits with high dominance effects and HT. When BayesB was fitted in one generation for predicting the next generation, the dominance inclusion increased the accuracies only for the oligogenic simulated trait with high dominance. Regardless of the model adopted, the accuracy of whole genotypic prediction decreased with the increase of dominance effects in simulated traits. Thus, these results reflect that dominance prediction is complex when compared to additive prediction, and for downstream applications of dominance effects, some genetic properties of the population should be evaluated, such as MAF and the number of half and full-sibs. In chapter 3, the inclusion of pedigree information in genomic model did not yield higher accuracies than models based in only marker information, and both models were substantially more accurate than models basedonly on pedigree. In HT, DBH and in polygenic traits simulated with additive-dominance effects, the RKHS-based models showed slightly higher accuracies than BayesA for whole genotypic prediction, while BayesA-based models were the best option for rust resistance and oligogenic simulated traits. For the prediction of breeding values, the BayesA additive was the best model.
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Flora, Gagan Deep. "Non-genomic effects of the Pregnane X Receptor (PXR) and Retinoid X Receptor (RXR) in platelets." Thesis, University of Reading, 2018. http://centaur.reading.ac.uk/80709/.
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Johansson, Tobias. "Neurosteroids Induce Allosteric Effects on the NMDA Receptor : Nanomolar Concentrations of Neurosteroids Exert Non-Genomic Effects on the NMDA Receptor Complex." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8503.
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The neurosteroids constitute a group of powerful hormones synthesized and acting in the central nervous system. They participate in a number of important central processes, such as memory and learning, mood and neuroprotection. Their effects emerge from rapid interactions with membrane bound receptors, such as the N-methyl-D-aspartate (NMDA) receptor, the gamma-amino-butyric acid receptor and the sigma 1 receptor. The mechanisms of action are separate from classical genomic interactions.
The aims of this thesis were to identify and characterize the molecular mechanisms underlying the effects of nanomolar concentrations of neurosteroids at the NMDA receptor.
The results show that the neurosteroids pregnenolone sulfate (PS) and pregnanolone sulfate 3α5βS) differently modulate the NMDA receptor, changing the kinetics for the NMDA receptor antagonist ifenprodil, through unique and separate targets at the NR2B subunit. The effects that appear to be temperature independent were further confirmed in a calcium imagining functional assay. A second functional study demonstrated that PS and 3α5βS affect glutamate-stimulated neurite outgrowth in NG108-15 cells.
Misuse of anabolic androgenic steroids (AAS) has powerful effects on emotional states. Since neurosteroids regulate processes involved in mood it can be hypothesised that AAS can interact with the action of neurosteroids in the brain. However, chronic administration of the AAS nandrolone decanoate did not alter the allosteric effects of PS or 3α5βS at the NMDA receptor, but changed the affinity for PS, 3α5βS and dehydroepiandrosterone sulfate to the sigma 1 receptor. The results also showed that the neurosteroids displace 3H-ifenprodil from the sigma 1 and 2 receptors without directly sharing the binding site for 3H-ifenprodil at the sigma 1 receptor. The decreased affinity for the neurosteroids at the sigma 1 receptor may be involved in the depressive symptoms associated with AAS misuse.
The NMDA receptor system is deeply involved in neurodegeneration and the NMDA receptor antagonist ifenprodil exert neuroprotective actions. The findings that neurosteroids interact with ifenprodil at the NMDA receptor may be an opportunity to obtain synergistic effects in neuroprotective treatment.
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Caddy, Joanne. "The non-genomic effects of the PPAR-γ ligand rosiglitazone on intracellular calcium concentrations in mammalian monocytic and smooth muscle cells." Thesis, Cardiff Metropolitan University, 2010. http://hdl.handle.net/10369/921.
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Thiazolidinediones such as rosiglitazone are used in the treatment of Type-2 Diabetes, and are ligands for peroxisome proliferator-activated receptor-gamma (PPARγ), a ligand-activated transcription factor that regulates expression of genes involved in glucose and lipid metabolism. However, rosiglitazone is known to exert PPARγ-independent effects alongside its classical receptor-dependent effects. This study investigated the PPARγ-independent effects of rosiglitazone on intracellular calcium (Ca2+i) signalling in cultured monocytic and vascular smooth muscle cells Rosiglitazone rapidly (5-30min) inhibited the Ca2+ sequestration activity of the ER-resident Ca2+ pump enzyme SERCA2b in a dose-dependent manner (IC50~2μM). 10μM Rosiglitazone triggered rapid increases in [Ca2+]i; however, restoration to basal levels occurred within 72h. Consequently, cell viability was not adversely affected by rosiglitazone treatment. Initiation of the unfolded protein response (UPR) was identified as the mechanism underpinning rosiglitazone's Ca2+ homeostatic restorative properties. Rosiglitazone induced alternate splicing of the UPR transcription factor XBP-1, which led to increased mRNA and protein expression of SERCA2b (shown via bioinformatics analysis to be a UPR target gene), and increased ER Ca2+-ATPase activity in rosiglitazone-treated cells. In tissue (rabbit aortic ring) samples, 10μM rosiglitazone induced transient (within 1h) non-significant losses in vasorelaxatory sensitivity to sodium nitroprusside, but extended treatment (4-24h) increased sensitivity beyond that of vehicle-treated samples. Thus, at cell and tissue levels, this data suggests that rosiglitazone initially causes increased [Ca2+]i due to inhibition of SERCA2b, but extended incubation induces - via upregulation of UPR target genes - the restoration of Ca2+ homeostasis, and possibly even improvements in function in some contexts. Clearly, the data presented in this in vitro study must be treated tentatively, and more research is needed before these potentially beneficial effects can be firmly identified as being clinically significant. Nevertheless, the data obtained here may constitute preliminary evidence that, alongside its PPARy-dependent effects, rosiglitazone may exert functional improvements on the vasculature.
Books on the topic "Non genomic effects"
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Martin, Wehling, ed. Genomic and non-genomic effects of aldosterone. Boca Raton: CRC Press, 1995.
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Hodgkiss, Andrew. Psychiatric consequences of cancer treatments: hormone and cytokine treatments. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198759911.003.0007.
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The antidepressant and neuroprotective effects of oestradiol are described. Psychiatric consequences of oophorectomy, and treatment with tamoxifen and aromatase inhibitors, are then discussed. Androgen-deprivation therapy has temporary effects on cognitive function and mood that reflect the distribution of androgen receptors in the brain. The rapid-onset adverse psychiatric effects of high-dose glucocorticoids are presented (including ‘steroid psychosis’) and a novel, non-genomic molecular mechanism highlighted. In contrast, the depressive effect of chronic glucocorticoid use is then considered.
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Rucker, James J. H., and Peter McGuffin. Copy Number Variation in Neuropsychiatric Disorders. Edited by Turhan Canli. Oxford University Press, 2013. http://dx.doi.org/10.1093/oxfordhb/9780199753888.013.005.
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It has long been known that the human genome is subject to deletion and duplication of genetic material by various molecular mechanisms. Until recently, such events were assumed to be relatively rare phenomena. It is now known that submicroscopic deletions or duplications calledcopy number variants(CNVs) are a major source of genomic variation. Rare CNVs (defined as occurring in less than 1 percent of the population) have been implicated in schizophrenia and autism. Measured in terms of odds ratios, individual CNVs have been shown to have large effects, some increasing the risk of disorder several-fold. But they are incompletely penetrant, no one CNV is either necessary or sufficient to cause the disorder. The findings are less clear-cut with bipolar disorder but, here, too, rare CNVs probably play a role. In unipolar depression, initial evidence suggests an overall increase in rare CNVs that disrupt exons, the coding regions of genes.
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Slack, Jonathan. 5. Genes of small effect. Oxford University Press, 2014. http://dx.doi.org/10.1093/actrade/9780199676507.003.0005.
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‘Genes of small effect’ considers unidentified genes whose variants collectively affect some characteristic of interest. Many aspects of living organisms depend not on the action of a few genes, but on the actions of many, each having a small effect on the overall characteristic. This assumption has been used successfully to inform the breeding of agricultural animals and plants. But some of the concepts have also been very controversial when applied to human beings. The heritability—the proportion of the variance in a population attributable to genetic variation—of human height, serious mental illness, and IQ is considered along with results from genome wide association studies.
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Levinson, Douglas F., and Walter E. Nichols. Genetics of Depression. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0024.
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Major depressive disorder (MDD) is a common and heterogeneous complex trait. Twin heritability is 35%–40%, perhaps higher in severe/recurrent cases. Adverse life events (particularly during childhood) increase risk. Current evidence suggests some overlap in genetic factors among MDD, bipolar disorder, and schizophrenia. Large genome-wide association studies (GWAS) are now proving successful. Polygenic effects of common SNPs are substantial. Findings implicate genes with effects on synaptic development and function, including two obesity-associated genes (NEGR1 and OLFM4), but not previous “candidate genes.” It can now be expected that larger GWAS samples will produce additional associations that shed new light on MDD genetics.
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Mitchell, Colter. The Genetics of Human Behavior. Edited by Rosemary L. Hopcroft. Oxford University Press, 2018. http://dx.doi.org/10.1093/oxfordhb/9780190299323.013.43.
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This chapter examines the recent massive expansion of genetic research into human behavior. Based on decades of twin research, there were high expectations of strong genetic effects for almost all behavior. Further work on candidate genes from animal research proved initially exciting. Although that research continues, it now currently receives much less attention, in contrast to whole-genome examinations. This chapter provides insight into the whole-genome era of behavioral research and the extent to which it may or may not be a profitable endeavor. Sociologists are generally unaware of this body of research, but it will likely continue to grow. The methods, strengths, and limitations of genome-wide work are discussed. A discussion of the future of this area and the extent to which this provides any leverage for social research of human behavior concludes the chapter.
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Vermeulen, Roel, Douglas A. Bell, Dean P. Jones, Montserrat Garcia-Closas, Avrum Spira, Teresa W. Wang, Martyn T. Smith, Qing Lan, and Nathaniel Rothman. Application of Biomarkers in Cancer Epidemiology. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0006.
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Advancements in OMICs are now enabling investigators to explore comprehensively the biological consequences of exogenous and endogenous exposures by detecting molecular signatures of exposure, early signs of adverse biological effects, preclinical disease, and molecularly defined cancer subtypes. These new technologies have proven invaluable for assembling a comprehensive portrait of human exposure, health, and disease. This includes hypothesis-driven biomarkers, as well as platforms that can agnostically analyze entire biologic processes and “compartments,” including the measurement of small molecules (metabolomics), DNA polymorphisms and rarer inherited variants (genomics), methylation and microRNA (epigenomics), chromosome-wide alterations, mRNA (transcriptomics), proteins (proteomics), and the microbiome (microbiomics). Although the implementation of these technologies in epidemiologic studies has already shown great promise, some challenges of particular importance must be addressed. Non-genetic OMIC markers vary over time due to both random variation and physiologic changes. Therefore, there is an urgent need for cohorts to collect repeat biological samples over time.
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Flinter, Frances. Ethical aspects of genetic testing. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0301_update_001.
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The increasing availability of genetic tests is transforming health care. Patients can benefit from earlier, more precise diagnosis and sometimes tailor-made treatment; their relatives can be offered pre-symptomatic, predictive tests and carrier tests. Physicians must balance confidentiality with duty to other individuals, and are responsible for using genetic tests for the benefit of patients in an ethical way. An offer of testing must balance potential additional benefit from potential downsides of testing including psychological effects, risk of error, continuing uncertainty, and cost. The ability to do multiple tests on many genes, even to sequence the whole genome, is rapidly approaching, and mainstreaming of tests means that geneticists are not necessarily involved. Further work and thinking needs to inform medical ethics in this area.
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Dalbeth, Nicola. Clinical features of gout. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198748311.003.0005.
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About 60% of the variance in serum urate levels can be explained by inherited genetic factors, but the extent of the contribution of genetic factors to gout in the presence of hyperuricaemia is not known. Genome-wide association studies in Europeans have identified 28 loci controlling serum urate levels, although the molecular basis of the majority of these genetic associations is currently unknown. The SLC2A9 and ABCG2 renal and gut uric acid transporters have very strong effects on urate levels and the risk of gout. Other uric acid transporters (e.g. SLC22A11/OAT478, SLC22A12/URAT1) and a glycolysis gene (GCKR) are associated with urate levels. Environmental exposures such as sugar-sweetened beverages and alcohol interact with urate-associated genetic variants in an unpredictable fashion. Very little is known about the genetic control of gout in the presence of hyperuricaemia, formation of monosodium urate crystals, and the immune response.
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Lewis, Myles, and Tim Vyse. Genetics of connective tissue diseases. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0042.
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The advent of genome-wide association studies (GWAS) has been an exciting breakthrough in our understanding of the genetic aetiology of autoimmune diseases. Substantial overlap has been found in susceptibility genes across multiple diseases, from connective tissue diseases and rheumatoid arthritis (RA) to inflammatory bowel disease, coeliac disease, and psoriasis. Major technological advances now permit genotyping of millions of single nucleotide polymorphisms (SNPs). Group analysis of SNPs by haplotypes, aided by completion of the Hapmap project, has improved our ability to pinpoint causal genetic variants. International collaboration to pool large-scale cohorts of patients has enabled GWAS in systemic lupus erythematosus (SLE), systemic sclerosis and Behçet's disease, with studies in progress for ANCA-associated vasculitis. These 'hypothesis-free' studies have revealed many novel disease-associated genes. In both SLE and systemic sclerosis, identified genes map to known pathways including antigen presentation (MHC, TNFSF4), autoreactivity of B and T lymphocytes (BLK, BANK1), type I interferon production (STAT4, IRF5) and the NFκB pathway (TNIP1). In SLE alone, additional genes appear to be involved in dysregulated apoptotic cell clearance (ITGAM, TREX1, C1q, C4) and recognition of immune complexes (FCGR2A, FCGR3B). Future developments include whole-genome sequencing to identify rare variants, and efforts to understand functional consequences of susceptibility genes. Putative environmental triggers for connective tissue diseases include infectious agents, especially Epstein-Barr virus; cigarette smoking; occupational exposure to toxins including silica; and low vitamin D, due to its immunomodulatory effects. Despite numerous studies looking at toxin exposure and connective tissue diseases, conclusive evidence is lacking, due to either rarity of exposure or rarity of disease.
Book chapters on the topic "Non genomic effects"
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Ramirez, V. D., and J. Zheng. "Non-Genomic Effects of Estrogens." In Estrogens and Antiestrogens I, 171–200. Berlin, Heidelberg: Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/978-3-642-58616-3_9.
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Farhat, Michel, Sylvie Abi-Younes, Roberto Vargas, Raymond M. Wolfe, Robert Clarke, and Peter W. Ramwell. "Vascular Non-genomic Effects of Estrogen." In Sex Steroids and the Cardiovascular System, 145–59. Berlin, Heidelberg: Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-662-02764-6_10.
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Pupo, Marco, Marcello Maggiolini, and Anna Maria Musti. "GPER Mediates Non-Genomic Effects of Estrogen." In Methods in Molecular Biology, 471–88. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3127-9_37.
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Montesinos López, Osval Antonio, Abelardo Montesinos López, and Jose Crossa. "Bayesian Genomic Linear Regression." In Multivariate Statistical Machine Learning Methods for Genomic Prediction, 171–208. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-89010-0_6.
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AbstractThe Bayesian paradigm for parameter estimation is introduced and linked to the main problem of genomic-enabled prediction to predict the trait of interest of the non-phenotyped individuals from genotypic information, environment variables, or other information (covariates). In this situation, a convenient practice is to include the individuals to be predicted in the posterior distribution to be sampled. We explained how the Bayesian Ridge regression method is derived and exemplified with data from plant breeding genomic selection. Other Bayesian methods (Bayes A, Bayes B, Bayes C, and Bayesian Lasso) were also described and exemplified for genome-based prediction. The chapter presented several examples that were implemented in the Bayesian generalized linear regression (BGLR) library for continuous response variables. The predictor under all these Bayesian methods includes main effects (of environments and genotypes) as well as interaction terms related to genotype × environment interaction.
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Sharma, Sahil, and Cynthia M. Sharma. "Identification of RNA Binding Partners of CRISPR-Cas Proteins in Prokaryotes Using RIP-Seq." In Methods in Molecular Biology, 111–33. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1851-6_6.
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AbstractCRISPR-Cas systems consist of a complex ribonucleoprotein (RNP) machinery encoded in prokaryotic genomes to confer adaptive immunity against foreign mobile genetic elements. Of these, especially the class 2, Type II CRISPR-Cas9 RNA-guided systems with single protein effector modules have recently received much attention for their application as programmable DNA scissors that can be used for genome editing in eukaryotes. While many studies have concentrated their efforts on improving RNA-mediated DNA targeting with these Type II systems, little is known about the factors that modulate processing or binding of the CRISPR RNA (crRNA) guides and the trans-activating tracrRNA to the nuclease protein Cas9, and whether Cas9 can also potentially interact with other endogenous RNAs encoded within the host genome. Here, we describe RIP-seq as a method to globally identify the direct RNA binding partners of CRISPR-Cas RNPs using the Cas9 nuclease as an example. RIP-seq combines co-immunoprecipitation (coIP) of an epitope-tagged Cas9 followed by isolation and deep sequencing analysis of its co-purified bound RNAs. This method can not only be used to study interactions of Cas9 with its known interaction partners, crRNAs and tracrRNA in native systems, but also to reveal potential additional RNA substrates of Cas9. For example, in RIP-seq analysis of Cas9 from the foodborne pathogen Campylobacter jejuni (CjeCas9), we recently identified several endogenous RNAs bound to CjeCas9 RNP in a crRNA-dependent manner, leading to the discovery of PAM-independent RNA cleavage activity of CjeCas9 as well as non-canonical crRNAs. RIP-seq can be easily adapted to any other effector RNP of choice from other CRISPR-Cas systems, allowing for the identification of target RNAs. Deciphering novel RNA-protein interactions for CRISPR-Cas proteins within host bacterial genomes will lead to a better understanding of the molecular mechanisms and functions of these systems and enable us to use the in vivo identified interaction rules as design principles for nucleic acid-targeting applications, fitted to each nuclease of interest.
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Hau, Kwan-Leong, Amelia Lane, Rosellina Guarascio, and Michael E. Cheetham. "Eye on a Dish Models to Evaluate Splicing Modulation." In Methods in Molecular Biology, 245–55. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2010-6_16.
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AbstractInherited retinal dystrophies, such as Leber congenital amaurosis, Stargardt disease, and retinitis pigmentosa, are characterized by photoreceptor dysfunction and death and currently have few treatment options. Recent technological advances in induced pluripotent stem cell (iPSC) technology and differentiation methods mean that human photoreceptors can now be studied in vitro. For example, retinal organoids provide a platform to study the development of the human retina and mechanisms of diseases in the dish, as well as being a potential source for cell transplantation. Here, we describe differentiation protocols for 3D cultures that produce retinal organoids containing photoreceptors with rudimentary outer segments. These protocols can be used as a model to understand retinal disease mechanisms and test potential therapies, including antisense oligonucleotides (AONs) to alter gene expression or RNA processing. This “retina in a dish” model is well suited for use with AONs, as the organoids recapitulate patient mutations in the correct genomic and cellular context, to test potential efficacy and examine off-target effects on the translational path to the clinic.
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Golz, Julia Carolin, and Kerstin Stingl. "Natural Competence and Horizontal Gene Transfer in Campylobacter." In Current Topics in Microbiology and Immunology, 265–92. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65481-8_10.
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AbstractThermophilic Campylobacter, in particular Campylobacter jejuni, C. coli and C. lari are the main relevant Campylobacter species for human infections. Due to their high capacity of genetic exchange by horizontal gene transfer (HGT), rapid adaptation to changing environmental and host conditions contribute to successful spreading and persistence of these foodborne pathogens. However, extensive HGT can exert dangerous side effects for the bacterium, such as the incorporation of gene fragments leading to disturbed gene functions. Here we discuss mechanisms of HGT, notably natural transformation, conjugation and bacteriophage transduction and limiting regulatory strategies of gene transfer. In particular, we summarize the current knowledge on how the DNA macromolecule is exchanged between single cells. Mechanisms to stimulate and to limit HGT obviously coevolved and maintained an optimal balance. Chromosomal rearrangements and incorporation of harmful mutations are risk factors for survival and can result in drastic loss of fitness. In Campylobacter, the restricted recognition and preferential uptake of free DNA from relatives are mediated by a short methylated DNA pattern and not by a classical DNA uptake sequence as found in other bacteria. A class two CRISPR-Cas system is present but also other DNases and restriction–modification systems appear to be important for Campylobacter genome integrity. Several lytic and integrated bacteriophages have been identified, which contribute to genome diversity. Furthermore, we focus on the impact of gene transfer on the spread of antibiotic resistance genes (resistome) and persistence factors. We discuss remaining open questions in the HGT field, supposed to be answered in the future by current technologies like whole-genome sequencing and single-cell approaches.
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Juarez, Paul D., Darryl B. Hood, Min-ae Song, and Aramandla Ramesh. "Applying an Exposome-wide Association Study (ExWAS) Approach to Latino Cancer Disparities." In Advancing the Science of Cancer in Latinos, 17–32. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-14436-3_2.
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AbstractLatinos have higher incidence rates of cervical, gall bladder, liver, and gastric cancer, and higher mortality rates for six cancer sites than US Whites. This review chapter focuses on Latino cancer disparities, how the exposome can be applied to understanding Latino cancer disparities, and how environmental exposures lead to alterations in key biological pathways at the cellular, molecular, and system level, helping to explain the increased risk for population level cancer disparities among Latinos. An exposome-wide association study (ExWAS) approach is proposed as a novel conceptual framework to assess the role of multiple chemical and non-chemical exposures in the cause and progression of cancer among Latinos across the life course. Also discussed is how this strategy could be exploited by using biomarkers of susceptibility, exposure, and effect; and how a trans-omics approach, using recent advances in genomics, epigenomics, transcriptomics, metabolomics, proteomics, and lipidomics, could be used to deploy new biomarkers that serve both prognostic and diagnostic purposes. Also outlined are the knowledge gaps and scope for future studies in this area with implications for public health and policy interventions.
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Reynolds, Matthew P., and Hans-Joachim Braun. "Wheat Improvement." In Wheat Improvement, 3–15. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-90673-3_1.
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AbstractWheat is a staple for rich and poor alike. Its improvement as a discipline was boosted when statisticians first distinguished heritable variation from environment effects. Many twentieth century crop scientists contributed to the Green Revolution that tripled yield potential of staple crops but yield stagnation is now a concern, especially considering the multiple challenges facing food security. Investments in modern technologies – phenomics, genomics etc. – provide tools to take both translational research and crop breeding to the next level. Herein wheat experts address three main themes: “Delivering Improved Germplasm” outlining theory and practice of wheat breeding and the attendant disciplines; ‘Translational Research to Incorporate Novel Traits’ covers biotic and abiotic challenges and outlines links between more fundamental research and crop breeding. However, effective translational research takes time and can be off-putting to funders and scientists who feel pressure to deliver near-term impacts. The final section ‘Rapidly Evolving Technologies & Likely Potential’ outlines methods that can boost translational research and breeding. The volume by being open access aims to disseminate a comprehensive textbook on wheat improvement to public and private wheat breeders globally, while serving as a benchmark of the current status as we address the formidable challenges that agriculture faces for the foreseeable future.
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Zhou, Li-bin, Yan Du, Zhuo Feng, Tao Cui, Xia Chen, Shan-wei Luo, Yu-ze Chen, et al. "Comparative study of mutations induced by carbon-ion beams and gamma-ray irradiations in Arabidopsis thaliana at the genome-wide scale." In Mutation breeding, genetic diversity and crop adaptation to climate change, 451–58. Wallingford: CABI, 2021. http://dx.doi.org/10.1079/9781789249095.0046.
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Abstract Mutation breeding induced by irradiation with highly energetic photons and ion beams is one of the important methods to improve plant varieties, but the mutagenic effects and molecular mechanisms are often not entirely clear. Traditional research is focused on phenotype screening, chromosome aberration tests and genetic variation analysis of specific genes. The whole genome sequencing technique provides a new method to understand and undertake the comprehensive identification of mutations caused by irradiations with different linear energy transfer (LET). In this study, ten Arabidopsis thaliana M3 lines induced by carbon-ion beams (CIB) and ten M3 lines induced by gamma-rays were re-sequenced by using the Illumina HiSeq sequencing platform, and the single base substitutions (SBSs) and small insertions or deletions (indels) were analysed comparatively. It was found that the ratio of SBSs to small indels for M3 lines induced by CIB was 2.57:1, whereas the ratio was 1.78:1 for gamma-rays. The ratios of deletions to insertions for carbon ions and gamma-rays were 4.8:1 and 2.8:1, respectively. The single-base indels were more prevalent than those equal to or greater than 2 bp in both CIB and gamma-ray induced M3 lines. Among the detected SBSs, the ratio of transitions to transversions induced by carbon-ion irradiation was 1.01 and 1.42 for gamma-rays; these values differ greatly from the 2.41 reported for spontaneous substitutions. This study provides novel data on molecular characteristics of CIB and gamma-ray induced mutations at the genome-wide scale. It can also provide valuable clues for explaining the potential mechanism of plant mutation breeding by irradiations with different LETs.
Conference papers on the topic "Non genomic effects"
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Adeel, Z., K. Kaczmarek, P. Ramos-Ramirez, and O. Tliba. "Non-Genomic Effects of Glucocorticoids Differentially Modulate Glucocorticoid Receptor Site-Specific Phosphorylation." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a2375.
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Razi, Abolfazl, Nilanjana Banerjee, Nevenka Dimitrova, and Vinay Varadan. "Non-linear Bayesian framework to determine the transcriptional effects of cancer-associated genomic aberrations." In 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2015. http://dx.doi.org/10.1109/embc.2015.7319885.
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He, Jiaxiu. "A study of the effects of non-specific filtering on the gene expression data prior to statistical testing." In 2011 IEEE International Workshop on Genomic Signal Processing and Statistics (GENSIPS). IEEE, 2011. http://dx.doi.org/10.1109/gensips.2011.6169482.
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Inoue, K., M. Nishio, Y. Inoue, M. Takeda, and H. Hirooka. "651. Genomic prediction with non-additive genetic effects for carcass weight and beef marbling in Japanese Black cattle." In World Congress on Genetics Applied to Livestock Production. The Netherlands: Wageningen Academic Publishers, 2022. http://dx.doi.org/10.3920/978-90-8686-940-4_651.
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Goetz, MP, M. Kuffel, KE Reinicke, Z. Huang, AM Bode, J. Cheng, T. Hoskin, et al. "Abstract P5-09-08: A comparison of the non-genomic effects of endoxifen and tamoxifen in aromatase inhibitor resistant breast cancer: Differential effects on the estrogen receptor co-regulator SRC3 (AIB1) and identification of PKC and PI3K as endoxifen substrates." In Abstracts: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium - Dec 10-14, 2013; San Antonio, TX. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/0008-5472.sabcs13-p5-09-08.
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Zambalde, Erika Pereira, Ana Carolina Rodrigues, Rubens Silveira Lima, Enilze Maria Souza Fonseca Ribeiro, and Jaqueline Carvalho Oliveira. "TLNC-UC.147, A NOVEL LONG RNA (lncRNA) FROM AN ULTRACONSERVED REGION AS POTENTIAL BIOMARKER IN LUMINAL A BREAST CANCER." In Scientifc papers of XXIII Brazilian Breast Congress - 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s1052.
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Introduction: Long RNAs are non-coding RNAs with more than 200 nucleotides in length, with essential regulatory roles in several biological processes, including in breast cancer (BC). The human genome contains 481 ultraconserved regions, which are genomic stretches of over 200 base pairs conserved among humans, rats, and mice. Most of these regions are transcriptionally active (T-UCRs), and several are differentially expressed in tumors. Some T-UCRs have been functionally characterized, but few have been associated with BC. Objectives: In this study, we aimed to expand the knowledge of T-UCRs in BC and characterize the lnc-uc.147, a long RNA transcribed from an ultraconserved region. Methods: We evaluated the expression level of 481 T-UCRs and their association with clinical parameters from TCGA data. For confirmation, 102 Brazilian BC samples were analyzed by RT-qPCR. Cytosolic and nuclear cell fractions and RT-qPCRs were done to determine the cell compartment of the transcript. Northern blotting and RACE were performed to determine the sequence and precise size of lnc-uc.147. Using two luminal cell lines (CAMA and BT474), a siRNA-based approach was applied to investigate the effects of lnc-uc.147 knockdown in cell viability, colony formation, and apoptosis level. To understand the interactions of lnc-uc.147 and proteins, we performed a pull-down assay. Results: Using TCGA (The Cancer Genome Atlas) data, we found 302 T-UCRs related to clinical features in BC: 43% were associated with molecular subtypes, 36% with estrogen-receptor positivity, 17% with HER2 expression, 12% with stage, and 10% with overall survival. We found that uc.147 is highly expressed in luminal A and B patients, which was also confirmed in Brazilian samples. For luminal A, a subtype usually associated with better prognosis, high uc.147 expression was associated with a poor prognosis and suggested as an independent prognostic factor. The lncRNA from uc.147 (lnc-uc.147) is in the nucleus. Northern blotting results show that uc.147 is a 2,8 kb monoexonic transcript. The silencing of uc.147 increases apoptosis, arrests the cell cycle and reduces cell viability and colony formation in luminal BC cell lines. Additionally, we identified 19 proteins that interact with uc.147 through mass spectrometry. These proteins are mainly involved in cytoskeletal and centrosome organization as well as in epithelial-mesenchymal transition. Conclusions: We show herein evidence that neoplastic BC cells exhibit a unique expression profile of T-UCRs. This study characterized the lnc-uc.147, a transcript that has never been described before. Indeed, lnc-uc.147 has an oncogenic effect in the luminal BC cell line and can interact with proteins. Furthermore, uc.147 has the potential as a BC prognostic marker in luminal patients.
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Younes, Nadin, Atiyeh Abdallah, and Marawan Abu madi. "A Whole-Genome Sequencing Association Study of Low Bone Mineral Density Identifies New Susceptibility Loci in the Phase I Qatar Biobank Cohort." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0115.
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Introduction: Bone density disorders are characterized by a reduction in bone mass density and strength, which lead to an increase in the susceptibility to sudden and unexpected fractures. Despite the serious consequences of low bone mineral density (BMD) and its significant impact on human health, most affected individuals may not know that they have the disease because it is asymptomatic. Therefore, understanding the genetic basis of low BMD and osteoporosis is essential to fully elucidate its pathobiology and devise preventative or therapeutic approaches. Materials and Methods: we sequenced the whole genomes of 3000 individuals from the Qatar Biobank and conducted genome-wide association analyses to identify genetic risk factors associated with low BMD in the Qatari population. Results: Fifteen variants were significantly associated with total body BMD (p < 5 × 10-8). Of these, five variants had previously been reported by and were directionally consistent with previous genome-wide association study data. Ten variants were new: six intronic variants located at six gene loci (MALAT1/TALAM1, FASLG, LSAMP, SAG, FAM189A2, and LOC101928063) and four intergenic variants. Conclusion: This first such study in Qatar provides a new insight into the genetic architecture of low BMD in the Qatari population. Nevertheless, more studies are needed to validate these findings and to elucidate the functional effects of these variants on low BMD and bone fracture susceptibility.
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Yoo, Seung Soo, Hyo-Gyoung Kang, Jin Eun Choi, Sun Ha Choi, So Yeon Lee, Shin Yup Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, and Jae Yong Park. "The effects of polymorphisms identified in genome-wide association studies of never-smoking females on the prognosis of non-small cell lung cancer." In ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.pa2873.
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Hammerman, James. "Statistics education on the sly: exploring large scientific data sets as an entrée to statistical ideas in secondary schools." In Next Steps in Statistics Education. International Association for Statistical Education, 2009. http://dx.doi.org/10.52041/srap.09802.
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Many large scientific and social scientific data sets—for example, those about climate and the environment, medicine, population or economic trends, the human genome, astronomy— are now widely available. As secondary students explore these data they investigate fascinating and important topics that can help them better participate as global citizens. However, understanding the meaning of these data requires statistical understandings—e.g., of variability amidst underlying aggregate trends, statistical control in complex relationships, the meaning of interaction effects, expectations about small probability events, statistical versus practical significance—that are difficult and rarely taught at the secondary level. This paper explores how interest in the science can motivate exploration of statistical ideas, at an informal if not rigorous technical level, which in turn can lead to a deeper understanding of scientific ideas. The role of data visualization and analysis tools to support this learning is also explored.
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Liu, Qiao, Chen Chen, Annie Gao, Hang Hang Tong, and Lei Xie. "VariFunNet, an integrated multiscale modeling framework to study the effects of rare non-coding variants in genome-wide association studies: Applied to Alzheimer's disease." In 2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). IEEE, 2017. http://dx.doi.org/10.1109/bibm.2017.8217995.
Full textReports on the topic "Non genomic effects"
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Fridman, Eyal, Jianming Yu, and Rivka Elbaum. Combining diversity within Sorghum bicolor for genomic and fine mapping of intra-allelic interactions underlying heterosis. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7597925.bard.
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Heterosis, the enigmatic phenomenon in which whole genome heterozygous hybrids demonstrate superior fitness compared to their homozygous parents, is the main cornerstone of modern crop plant breeding. One explanation for this non-additive inheritance of hybrids is interaction of alleles within the same locus. This proposal aims at screening, identifying and investigating heterosis trait loci (HTL) for different yield traits by implementing a novel integrated mapping approach in Sorghum bicolor as a model for other crop plants. Originally, the general goal of this research was to perform a genetic dissection of heterosis in a diallel built from a set of Sorghum bicolor inbred lines. This was conducted by implementing a novel computational algorithm which aims at associating between specific heterozygosity found among hybrids with heterotic variation for different agronomic traits. The initial goals of the research are: (i) Perform genotype by sequencing (GBS) of the founder lines (ii) To evaluate the heterotic variation found in the diallel by performing field trails and measurements in the field (iii) To perform QTL analysis for identifying heterotic trait loci (HTL) (iv) to validate candidate HTL by testing the quantitative mode of inheritance in F2 populations, and (v) To identify candidate HTL in NAM founder lines and fine map these loci by test-cross selected RIL derived from these founders. The genetic mapping was initially achieved with app. 100 SSR markers, and later the founder lines were genotyped by sequencing. In addition to the original proposed research we have added two additional populations that were utilized to further develop the HTL mapping approach; (1) A diallel of budding yeast (Saccharomyces cerevisiae) that was tested for heterosis of doubling time, and (2) a recombinant inbred line population of Sorghum bicolor that allowed testing in the field and in more depth the contribution of heterosis to plant height, as well as to achieve novel simulation for predicting dominant and additive effects in tightly linked loci on pseudooverdominance. There are several conclusions relevant to crop plants in general and to sorghum breeding and biology in particular: (i) heterosis for reproductive (1), vegetative (2) and metabolic phenotypes is predominantly achieved via dominance complementation. (ii) most loci that seems to be inherited as overdominant are in fact achieving superior phenotype of the heterozygous due to linkage in repulsion, namely by pseudooverdominant mechanism. Our computer simulations show that such repulsion linkage could influence QTL detection and estimation of effect in segregating populations. (iii) A new height QTL (qHT7.1) was identified near the genomic region harboring the known auxin transporter Dw3 in sorghum, and its genetic dissection in RIL population demonstrated that it affects both the upper and lower parts of the plant, whereas Dw3 affects only the part below the flag leaf. (iv) HTL mapping for grain nitrogen content in sorghum grains has identified several candidate genes that regulate this trait, including several putative nitrate transporters and a transcription factor belonging to the no-apical meristem (NAC)-like large gene family. This activity was combined with another BARD-funded project in which several de-novo mutants in this gene were identified for functional analysis.
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Weller, Joel I., Derek M. Bickhart, Micha Ron, Eyal Seroussi, George Liu, and George R. Wiggans. Determination of actual polymorphisms responsible for economic trait variation in dairy cattle. United States Department of Agriculture, January 2015. http://dx.doi.org/10.32747/2015.7600017.bard.
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The project’s general objectives were to determine specific polymorphisms at the DNA level responsible for observed quantitative trait loci (QTLs) and to estimate their effects, frequencies, and selection potential in the Holstein dairy cattle breed. The specific objectives were to (1) localize the causative polymorphisms to small chromosomal segments based on analysis of 52 U.S. Holstein bulls each with at least 100 sons with high-reliability genetic evaluations using the a posteriori granddaughter design; (2) sequence the complete genomes of at least 40 of those bulls to 20 coverage; (3) determine causative polymorphisms based on concordance between the bulls’ genotypes for specific polymorphisms and their status for a QTL; (4) validate putative quantitative trait variants by genotyping a sample of Israeli Holstein cows; and (5) perform gene expression analysis using statistical methodologies, including determination of signatures of selection, based on somatic cells of cows that are homozygous for contrasting quantitative trait variants; and (6) analyze genes with putative quantitative trait variants using data mining techniques. Current methods for genomic evaluation are based on population-wide linkage disequilibrium between markers and actual alleles that affect traits of interest. Those methods have approximately doubled the rate of genetic gain for most traits in the U.S. Holstein population. With determination of causative polymorphisms, increasing the accuracy of genomic evaluations should be possible by including those genotypes as fixed effects in the analysis models. Determination of causative polymorphisms should also yield useful information on gene function and genetic architecture of complex traits. Concordance between QTL genotype as determined by the a posteriori granddaughter design and marker genotype was determined for 30 trait-by-chromosomal segment effects that are segregating in the U.S. Holstein population; a probability of <10²⁰ was used to accept the null hypothesis that no segregating gene within the chromosomal segment was affecting the trait. Genotypes for 83 grandsires and 17,217 sons were determined by either complete sequence or imputation for 3,148,506 polymorphisms across the entire genome. Variant sites were identified from previous studies (such as the 1000 Bull Genomes Project) and from DNA sequencing of bulls unique to this project, which is one of the largest marker variant surveys conducted for the Holstein breed of cattle. Effects for stature on chromosome 11, daughter pregnancy rate on chromosome 18, and protein percentage on chromosome 20 met 3 criteria: (1) complete or nearly complete concordance, (2) nominal significance of the polymorphism effect after correction for all other polymorphisms, and (3) marker coefficient of determination >40% of total multiple-regression coefficient of determination for the 30 polymorphisms with highest concordance. The missense polymorphism Phe279Tyr in GHR at 31,909,478 base pairs on chromosome 20 was confirmed as the causative mutation for fat and protein concentration. For effect on fat percentage, 12 additional missensepolymorphisms on chromosome 14 were found that had nearly complete concordance with the suggested causative polymorphism (missense mutation Ala232Glu in DGAT1). The markers used in routine U.S. genomic evaluations were increased from 60,000 to 80,000 by adding markers for known QTLs and markers detected in BARD and other research projects. Objectives 1 and 2 were completely accomplished, and objective 3 was partially accomplished. Because no new clear-cut causative polymorphisms were discovered, objectives 4 through 6 were not completed.
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Zhao, Bingyu, Saul Burdman, Ronald Walcott, and Gregory E. Welbaum. Control of Bacterial Fruit Blotch of Cucurbits Using the Maize Non-Host Disease Resistance Gene Rxo1. United States Department of Agriculture, September 2013. http://dx.doi.org/10.32747/2013.7699843.bard.
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The specific objectives of this BARD proposal were: (1) To determine whether Rxol can recognize AacavrRxo1 to trigger BFB disease resistance in stable transgenic watermelon plants. (2) To determine the distribution of Aac-avrRxo1 in a global population of Aae and to characterize the biological function of Aac-avrRxo1. (3) To characterize other TIS effectors of Aae and to identify plant R gene(s) that can recognize conserved TIS effectors of this pathogen. Background to the topic: Bacterial fruit blotch (BFB) of cucurbits, caused by Acidovorax avenae subsp. citrulli (Aae), is a devastating disease that affects watermelon (Citrullus lanatus) and melon (Cucumis melo) production worldwide, including both Israel and USA. Two major groups of Aae strains have been classified based on their virulence on host plants, genetics and biochemical properties. Thus far, no effective resistance genes have been identified from cucurbit germplasm. In this project, we assessed the applicability of a non-host disease resistance gene, Rxol, to control BFB in watermelon. We also tried to identify Aae type III secreted (TIS) effectors that can be used as molecular probes to identify novel disease resistance genes in both cucurbits and Nieotianatabaeum. Major conclusions, solutions, achievements: We generated five independent transgenic watermelon (cv. Sugar Babay) plants expressing the Rxol gene. The transgenic plants were evaluated with Aae strains AAC001 and M6 under growth chamber conditions. All transgenic plants were found to be susceptible to both Aae strains. It is possible that watermelon is missing other signaling components that are required for Rxol-mediated disease resistance. In order to screen for novel BFB resistance genes, we inoculated two Aae strains on 60 Nieotiana species. Our disease assay revealed Nicotiana tabaeum is completely resistant to Aae, while its wild relative N. benthamiana is susceptible to Aae. We further demonstrated that Nieotiana benthamiana can be used as a surrogate host for studying the mechanisms of pathogenesis of Aae. We cloned 11 TIS effector genes including the avrRxolhomologues from the genomes of 22 Aae strains collected worldwide. Sequencing analysis revealed that functional avrRxol is conserved in group" but not group I Aae strains. Three effector genes- Aave_1548, Aave_2166 and Aave_2708- possessed the ability to trigger an HR response in N. tabacum when they were transiently expressed by Agrobaeterium. We conclude that N. tabacum carries at least three different non-host resistance genes that can specifically recognize AaeTIS effectors to trigger non-host resistance. Screening 522 cucurbits genotypes with two Aae strains led us to identify two germplasm (P1536473 and P1273650) that are partially resistant to Aae. Interestingly, transient expression of the TIS effector, Aave_1548, in the two germplasms also triggered HR-Iike cell death, which suggests the two lines may carry disease resistance genes that can recognize Aave_1548. Importantly, we also demonstrated that this effector contributes to the virulence of the bacterium in susceptible plants. Therefore, R genes that recognize effector Aave1548 have great potential for breeding for BFB resistance. To better understand the genome diversity of Aae strains, we generated a draft genome sequence of the Israeli Aae strain, M6 (Group I) using Iliumina technology. Comparative analysis of whole genomes of AAC001, and M6 allowed us to identify several effectors genes that differentiate groups I and II. Implications, both scientific and agricultural: The diversity of TIS effectors in group I and II strains of Aae suggests that a subset of effectors could contribute to the host range of group I and II Aae strains. Analysis of these key effectors in a larger Aae population may allow us to predict which cucurbit hosts may be at risk to BFB. Additionally, isolation of tobacco and cucurbit Rgenes that can recognize Aae type III effectors may offer new genetic resources for controlling BFB.
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Gur, Amit, Edward Buckler, Joseph Burger, Yaakov Tadmor, and Iftach Klapp. Characterization of genetic variation and yield heterosis in Cucumis melo. United States Department of Agriculture, January 2016. http://dx.doi.org/10.32747/2016.7600047.bard.
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Project objectives: 1) Characterization of variation for yield heterosis in melon using Half-Diallele (HDA) design. 2) Development and implementation of image-based yield phenotyping in melon. 3) Characterization of genetic, epigenetic and transcriptional variation across 25 founder lines and selected hybrids. The epigentic part of this objective was modified during the course of the project: instead of characterization of chromatin structure in a single melon line through genome-wide mapping of nucleosomes using MNase-seq approach, we took advantage of rapid advancements in single-molecule sequencing and shifted the focus to Nanoporelong-read sequencing of all 25 founder lines. This analysis provides invaluable information on genome-wide structural variation across our diversity 4) Integrated analyses and development of prediction models Agricultural heterosis relates to hybrids that outperform their inbred parents for yield. First generation (F1) hybrids are produced in many crop species and it is estimated that heterosis increases yield by 15-30% globally. Melon (Cucumismelo) is an economically important species of The Cucurbitaceae family and is among the most important fleshy fruits for fresh consumption Worldwide. The major goal of this project was to explore the patterns and magnitude of yield heterosis in melon and link it to whole genome sequence variation. A core subset of 25 diverse lines was selected from the Newe-Yaar melon diversity panel for whole-genome re-sequencing (WGS) and test-crosses, to produce structured half-diallele design of 300 F1 hybrids (MelHDA25). Yield variation was measured in replicated yield trials at the whole-plant and at the rootstock levels (through a common-scion grafted experiments), across the F1s and parental lines. As part of this project we also developed an algorithmic pipeline for detection and yield estimation of melons from aerial-images, towards future implementation of such high throughput, cost-effective method for remote yield evaluation in open-field melons. We found extensive, highly heritable root-derived yield variation across the diallele population that was characterized by prominent best-parent heterosis (BPH), where hybrids rootstocks outperformed their parents by 38% and 56 % under optimal irrigation and drought- stress, respectively. Through integration of the genotypic data (~4,000,000 SNPs) and yield analyses we show that root-derived hybrids yield is independent of parental genetic distance. However, we mapped novel root-derived yield QTLs through genome-wide association (GWA) analysis and a multi-QTLs model explained more than 45% of the hybrids yield variation, providing a potential route for marker-assisted hybrid rootstock breeding. Four selected hybrid rootstocks are further studied under multiple scion varieties and their validated positive effect on yield performance is now leading to ongoing evaluation of their commercial potential. On the genomic level, this project resulted in 3 layers of data: 1) whole-genome short-read Illumina sequencing (30X) of the 25 founder lines provided us with 25 genome alignments and high-density melon HapMap that is already shown to be an effective resource for QTL annotation and candidate gene analysis in melon. 2) fast advancements in long-read single-molecule sequencing allowed us to shift focus towards this technology and generate ~50X Nanoporesequencing of the 25 founders which in combination with the short-read data now enable de novo assembly of the 25 genomes that will soon lead to construction of the first melon pan-genome. 3) Transcriptomic (3' RNA-Seq) analysis of several selected hybrids and their parents provide preliminary information on differentially expressed genes that can be further used to explain the root-derived yield variation. Taken together, this project expanded our view on yield heterosis in melon with novel specific insights on root-derived yield heterosis. To our knowledge, thus far this is the largest systematic genetic analysis of rootstock effects on yield heterosis in cucurbits or any other crop plant, and our results are now translated into potential breeding applications. The genomic resources that were developed as part of this project are putting melon in the forefront of genomic research and will continue to be useful tool for the cucurbits community in years to come.
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Abbott, Albert G., Doron Holland, Douglas Bielenberg, and Gregory Reighard. Structural and Functional Genomic Approaches for Marking and Identifying Genes that Control Chilling Requirement in Apricot and Peach Trees. United States Department of Agriculture, September 2009. http://dx.doi.org/10.32747/2009.7591742.bard.
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Structural and functional genomic approaches for marking and identifying genes that control chilling requirement in apricot and peach trees. Specific aims: 1) Identify and characterize the genetic nature of chilling requirement for flowering and dormancy break of vegetative shoots in Prunusgermplasm through the utilization of existing apricot (NeweYa'ar Research Center, ARO) and peach (Clemson University) genetic mapping populations; 2) Use molecular genetic mapping techniques to identify markers flanking genomic regions controlling chilling; 3) Comparatively map the regions controlling chilling requirement in apricot and peach and locate important genomic regions influencing chilling requirement on the Prunus functional genomic database as an initial step for identification of candidate genes; 4) Develop from the functional genomics database a set of markers facilitating the development of cultivars with optimized chilling requirements for improved and sustained fruit production in warm-winter environments. Dormant apricot (prunus armeniaca L.) and peach [Prunus persica (L.) Batsch] trees require sustained exposure to low, near freezing, temperatures before vigorous floral and vegetative bud break is possible after the resumption of warm temperatures in the spring. The duration of chilling required (the chilling requirement, CR) is determined by the climatic adaptation of the particular cultivar, thus limiting its geographic distribution. This limitation is particularly evident when attempting to introduce superior cultivars to regions with very warm winter temperatures, such as Israel and the coastal southern United States. The physiological mechanism of CR is not understood and although breeding programs deliberately manipulate CR in apricot and peach crosses, robust closely associated markers to the trait are currently not available. We used segregating populations of apricot (100 Fl individuals, NeweYa'ar Research Center, ARO) and peach (378 F2 individuals, Clemson University) to discover several discreet genomic loci that regulate CR and blooming date. We used the extensive genomic/genetic resources available for Prunus to successfully combine our apricot and peach genetic data and identify five QTL with strong effects that are conserved between species as well as several QTL that are unique to each species. We have identified markers in the key major QTL regions for testing in breeding programs which we are carrying out currently; we have identified an initial set of candidate genes using the peach physical/transcriptome map and whole peach genome sequences and we are testing these currently to identify key target genes for manipulation in breeding programs. Our collaborative work to date has demonstrated the following: 1) CR in peach and apricot is predominantly controlled by a limited number ofQTL loci, seven detected in a peach F2 derived map comprising 65% of the character and 12 in an apricot Fl map comprising 71.6% and 55.6% of the trait in the Perfection and A. 1740 parental maps, respectively and that peach and apricot appear in our initial maps to share five genomic intervals containing potentially common QTL. 2) Application of common anchor markers of the Prunus/peach, physical/genetic map resources has allowed us not only to identify the shared intervals but also to have immediately available some putative candidate gene information from these intervals, the EVG region on LG1 in peach the TALY 1 region in apricot on LG2 in peach; and several others involved in vernalization pathways (LGI and LG7). 3) Mapped BACcontigs are easily defined from the complete physical map resources in peach through the common SSR markers that anchor our CR maps in the two species, 4) Sequences of BACs in these regions can be easily mined for additional polymorphic markers to use in MAS applications.
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Weller, Joel I., Ignacy Misztal, and Micha Ron. Optimization of methodology for genomic selection of moderate and large dairy cattle populations. United States Department of Agriculture, March 2015. http://dx.doi.org/10.32747/2015.7594404.bard.
Full textAbstract:
The main objectives of this research was to detect the specific polymorphisms responsible for observed quantitative trait loci and develop optimal strategies for genomic evaluations and selection for moderate (Israel) and large (US) dairy cattle populations. A joint evaluation using all phenotypic, pedigree, and genomic data is the optimal strategy. The specific objectives were: 1) to apply strategies for determination of the causative polymorphisms based on the “a posteriori granddaughter design” (APGD), 2) to develop methods to derive unbiased estimates of gene effects derived from SNP chips analyses, 3) to derive optimal single-stage methods to estimate breeding values of animals based on marker, phenotypic and pedigree data, 4) to extend these methods to multi-trait genetic evaluations and 5) to evaluate the results of long-term genomic selection, as compared to traditional selection. Nearly all of these objectives were met. The major achievements were: The APGD and the modified granddaughter designs were applied to the US Holstein population, and regions harboring segregating quantitative trait loci (QTL) were identified for all economic traits of interest. The APGD was able to find segregating QTL for all the economic traits analyzed, and confidence intervals for QTL location ranged from ~5 to 35 million base pairs. Genomic estimated breeding values (GEBV) for milk production traits in the Israeli Holstein population were computed by the single-step method and compared to results for the two-step method. The single-step method was extended to derive GEBV for multi-parity evaluation. Long-term analysis of genomic selection demonstrated that inclusion of pedigree data from previous generations may result in less accurate GEBV. Major conclusions are: Predictions using single-step genomic best linear unbiased prediction (GBLUP) were the least biased, and that method appears to be the best tool for genomic evaluation of a small population, as it automatically accounts for parental index and allows for inclusion of female genomic information without additional steps. None of the methods applied to the Israeli Holstein population were able to derive GEBV for young bulls that were significantly better than parent averages. Thus we confirm previous studies that the main limiting factor for the accuracy of GEBV is the number of bulls with genotypes and progeny tests. Although 36 of the grandsires included in the APGD were genotyped for the BovineHDBeadChip, which includes 777,000 SNPs, we were not able to determine the causative polymorphism for any of the detected QTL. The number of valid unique markers on the BovineHDBeadChip is not sufficient for a reasonable probability to find the causative polymorphisms. Complete resequencing of the genome of approximately 50 bulls will be required, but this could not be accomplished within the framework of the current project due to funding constraints. Inclusion of pedigree data from older generations in the derivation of GEBV may result is less accurate evaluations.
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Soller, Moshe (Morris), Hans Cheng, and Lyman Crittenden. Mapping the Chicken Genome, Including Loci Affecting Traits of Economic Importance. United States Department of Agriculture, September 1994. http://dx.doi.org/10.32747/1994.7568779.bard.
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A total of 195 microsatellites were added to the chicken genome map. Mapping of fifty known genes revealed a high degree of conserved linkage order between human and chicken genomes. A new, statistically powerful mapping design, the full-sib intercross line (produced by mating two parents, and intercrossing their progeny over a number of generations), was developed for use in species with high reproductive capacity. The Jerusalem Resource Population (JRP), now at the F12 generation, was established to implement this design i chickens. The biometrical picutre in the JRP is similar to that generally found in chicken populations; inbreeding effects were not observed. The F2 and F3 generations of the JRP were genotyped with respect to twelve production traits, using a battery of 23 microsatellites markers. The number of significant effects was twice that expected on chance alone, validating the high statistical power of the JRP with respect to QTL differentiating the parental lines. Selective DNA pooling, based on estimation of marker allele frequencies in pooled DNA samples, has been proposed to reduce high genotyping costs of QTL mapping. A method to correct for overlapping shadow bands of dinucleotide microsatellite markers in pooled DNA samples was developed and validated. In a retrospective study using this procedure, previously mapped loci affecting Marek's disease were successfully identified.
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Palmer, Guy, Varda Shkap, Wendy Brown, and Thea Molad. Control of bovine anaplasmosis: cytokine enhancement of vaccine efficacy. United States Department of Agriculture, March 2007. http://dx.doi.org/10.32747/2007.7695879.bard.
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Anaplasmosis an arthropod-born disease of cattle caused by the rickettsia Anaplasma marginale and is an impediment to efficient production of healthy livestock in both Israel and the United States. Currently the only effective vaccines are derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Consequently development of a safe, effective vaccine is a high priority. In this collaborative project we focused on two approaches to vaccine development. The first focused o n improving antigen delivery to livestock and specifically examined how DNA vaccines could be improved to enhance priming and expansion of the immune response. This research resulted in development and testing of two novel vaccine delivery systems--one that targeted antigen spread among dendritic cells (the key cell in priming immune responses and a follow-on construct that also specifically targeted antigen to the endosomal-lysosomal compartment the processing organelle within the dendritic cell that directs vaccine antigen to the MHC class ll-CD4* T cell priming pathway). The optimized construct targeting vaccine antigen to the dendritic cell MHC class II pathway was tested for ability to prime A. marginale specific immune responses in outbred cattle. The results demonstrated both statistically significant effects of priming with a single immunization, continued expansion of the primary immune response including development of high affinity lgG antibodies and rapid recall of the memory response following antigen challenge. This portion of the study represented a significant advance in vaccine delivery for livestock. Importantly the impact of these studies is not limited to A. marginale a s the targeting motifs are optimized for cattle and can be adapted to other cattle vaccinations by inserting a relevant pathogen-specific antigen. The second approach (which represented an addition to the project for which approval was requested as part of the first annual report) was a comparative approach between A . marginale and the Israel A . centrale vaccines train. This addition was requested as studies on Major Surface Protein( MSP)- 2 have shown that this antigen is highly antigenically variable and presented solely as a "static vaccine" antigen does not give cross-strain immunity. In contrast A. . centrale is an effective vaccine which Kimron Veterinary institute has used in the field in Israel for over 50 years. Taking advantage of this expertise, a broad comparison of wild type A. marginale and vaccine strain was initiated. These studies revealed three primary findings: i) use of the vaccine is associated with superinfection, but absence of clinical disease upon superinfection with A. marginale; ii) the A. centrale vaccine strain is not only less virulent but transmission in competent in Dermacentor spp. ticks; and iii) some but not all MSPs are conserved in basic orthologous structure but there are significant polymorphisms among the strains. These studies clearly indicated that there are statistically significant differences in biology (virulence and transmission) and provide a clear path for mapping of biology with the genomes. Based on these findings, we initiated complete genome sequencing of the Israel vaccine strain (although not currently funded by BARD) and plant to proceed with a comparative genomics approach using already sequenced wild-type A. marginale. These findings and ongoing collaborative research tie together filed vaccine experience with new genomic data, providing a new approach to vaccine development against a complex pathogen.
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Cohen, Yuval, Christopher A. Cullis, and Uri Lavi. Molecular Analyses of Soma-clonal Variation in Date Palm and Banana for Early Identification and Control of Off-types Generation. United States Department of Agriculture, October 2010. http://dx.doi.org/10.32747/2010.7592124.bard.
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Date palm (Phoenix dactylifera L.) is the major fruit tree grown in arid areas in the Middle East and North Africa. In the last century, dates were introduced to new regions including the USA. Date palms are traditionally propagated through offshoots. Expansion of modern date palm groves led to the development of Tissue Culture propagation methods that generate a large number of homogenous plants, have no seasonal effect on plant source and provide tools to fight the expansion of date pests and diseases. The disadvantage of this procedure is the occurrence of off-type trees which differ from the original cultivar. In the present project we focused on two of the most common date palm off-types: (1) trees with reduced fruit setting, in which most of the flowers turn into three-carpel parthenocarpic fruits. In a severe form, multi-carpel flowers and fruitlets (with up to six or eight carpels instead of the normal three-carpel flowers) are also formed. (2) dwarf trees, having fewer and shorter leaves, very short trunk and are not bearing fruits at their expected age, compared to the normal trees. Similar off-types occur in other crop species propagated by tissue culture, like banana (mainly dwarf plants) or oil palm (with a common 'Mantled' phenotype with reduced fruit setting and occurrence of supernumerary carpels). Some off-types can only be detected several years after planting in the fields. Therefore, efficient methods for prevention of the generation of off-types, as well as methods for their detection and early removal, are required for date palms, as well as for other tissue culture propagated crops. This research is aimed at the understanding of the mechanisms by which off-types are generated, and developing markers for their early identification. Several molecular and genomic approaches were applied. Using Methylation Sensitive AFLP and bisulfite sequencing, we detected changes in DNA methylation patterns occurring in off-types. We isolated and compared the sequence and expression of candidate genes, genes related to vegetative growth and dwarfism and genes related to flower development. While no sequence variation were detected, changes in gene expression, associated with the severity of the "fruit set" phenotype were detected in two genes - PdDEF (Ortholog of rice SPW1, and AP3 B type MADS box gene), and PdDIF (a defensin gene, highly homologous to the oil palm gene EGAD). We applied transcriptomic analyses, using high throughput sequencing, to identify genes differentially expressed in the "palm heart" (the apical meristem and the region of embryonic leaves) of dwarf vs. normal trees. Among the differentially expressed genes we identified genes related to hormonal biosynthesis, perception and regulation, genes related to cell expansion, and genes related to DNA methylation. Using Representation Difference Analyses, we detected changes in the genomes of off-type trees, mainly chloroplast-derived sequences that were incorporated in the nuclear genome and sequences of transposable elements. Sequences previously identified as differing between normal and off-type trees of oil palms or banana, successfully identified variation among date palm off-types, suggesting that these represent highly labile regions of monocot genomes. The data indicate that the date palm genome, similarly to genomes of other monocot crops as oil palm and banana, is quite unstable when cells pass through a cycle of tissue culture and regeneration. Changes in DNA sequences, translocation of DNA fragments and alteration of methylation patterns occur. Consequently, patterns of gene expression are changed, resulting in abnormal phenotypes. The data can be useful for future development of tools for early identification of off-type as well as for better understanding the phenomenon of somaclonal variation during propagation in vitro.
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Kuiken, Todd, and Jennifer Kuzma. Genome Editing in Latin America: Regional Regulatory Overview. Inter-American Development Bank, July 2021. http://dx.doi.org/10.18235/0003410.
Full textAbstract:
The power and promise of genome editing, CRISPR specifically, was first realized with the discovery of CRISPR loci in the 1980s.3 Since that time, CRISPR-Cas systems have been further developed enabling genome editing in virtually all organisms across the tree of life.3 In the last few years, we have seen the development of a diverse set of CRISPR-based technologies that has revolutionized genome manipulation.4 Enabling a more diverse set of actors than has been seen with other emerging technologies to redefine research and development for biotechnology products encompassing food, agriculture, and medicine.4 Currently, the CRISPR community encompasses over 40,000 authors at 20,000 institutions that have documented their research in over 20,000 published and peer-reviewed studies.5 These CRISPR-based genome editing tools have promised tremendous opportunities in agriculture for the breeding of crops and livestock across the food supply chain. Potentially addressing issues associated with a growing global population, sustainability concerns, and possibly help address the effects of climate change.4 These promises however, come along-side concerns of environmental and socio-economic risks associated with CRISPR-based genome editing, and concerns that governance systems are not keeping pace with the technological development and are ill-equipped, or not well suited, to evaluate these risks. The Inter-American Development Bank (IDB) launched an initiative in 2020 to understand the complexities of these new tools, their potential impacts on the LAC region, and how IDB may best invest in its potential adoption and governance strategies. This first series of discussion documents: “Genome Editing in Latin America: Regulatory Overview,” and “CRISPR Patent and Licensing Policy” are part of this larger initiative to examine the regulatory and institutional frameworks surrounding gene editing via CRISPR-based technologies in the Latin America and Caribbean (LAC) regions. Focusing on Argentina, Bolivia, Brazil, Colombia, Honduras, Mexico, Paraguay, Peru, and Uruguay, they set the stage for a deeper analysis of the issues they present which will be studied over the course of the next year through expert solicitations in the region, the development of a series of crop-specific case studies, and a final comprehensive regional analysis of the issues discovered.