scholarly journals Aneuploidy and DNA Methylation as Mirrored Features of Early Human Embryo Development

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1084
Author(s):  
Ekaterina N. Tolmacheva ◽  
Stanislav A. Vasilyev ◽  
Igor N. Lebedev

Genome stability is an integral feature of all living organisms. Aneuploidy is the most common cause of fetal death in humans. The timing of bursts in increased aneuploidy frequency coincides with the waves of global epigenetic reprogramming in mammals. During gametogenesis and early embryogenesis, parental genomes undergo two waves of DNA methylation reprogramming. Failure of these processes can critically affect genome stability, including chromosome segregation during cell division. Abnormal methylation due to errors in the reprogramming process can potentially lead to aneuploidy. On the other hand, the presence of an entire additional chromosome, or chromosome loss, can affect the global genome methylation level. The associations of these two phenomena are well studied in the context of carcinogenesis, but here, we consider the relationship of DNA methylation and aneuploidy in early human and mammalian ontogenesis. In this review, we link these two phenomena and highlight the critical ontogenesis periods and genome regions that play a significant role in human reproduction and in the formation of pathological phenotypes in newborns with chromosomal aneuploidy.

2019 ◽  
Vol 48 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Robert A Philibert ◽  
Meeshanthini V Dogan ◽  
James A Mills ◽  
Jeffrey D Long

Background.—The ability to predict mortality is useful to clinicians, policy makers and insurers. At the current time, prediction of future mortality is still an inexact process with some proposing that epigenetic assessments could play a role in improving prognostics. In past work, we and others have shown that DNA methylation status at cg05575921, a well-studied measure of smoking intensity, is also a predictor of mortality. However, the exact extent of that predictive capacity and its independence of other commonly measured mortality risk factors are unknown. Objective.—To determine the capacity of methylation to predict mortality. Method.—We analyzed the relationship of methylation at cg05575921 and cg04987734, a recently described quantitative marker of heavy alcohol consumption, to mortality in the Offspring Cohort of the Framingham Heart Study using proportional hazards survival analysis. Results.—In this group of participants (n = 2278) whose average age was 66 ± 9 years, we found that the inclusion of both cg05575921 and cg04987734 methylation to a base model consisting of age and sex only, or to a model containing 11 commonly used mortality risk factors, improved risk prediction. What is more, prediction accuracy for the base model plus methylation data was increased compared to the base model plus known predictors of mortality (CHD, COPD, or stroke). Conclusion.—Cg05575921, and to a smaller extent cg04987734, are strong predictors of mortality risk in older Americans and that incorporation of DNA methylation assessments to these and other loci may be useful to population scientists, actuaries and policymakers to better understand the relationship of environmental risk factors, such as smoking and drinking, to mortality.


2017 ◽  
Vol 12 (1) ◽  
pp. S537-S538
Author(s):  
Koichiro Kajiura ◽  
Kazuya Kondo ◽  
Toru Sawada ◽  
Naoya Kawakita ◽  
Mitsuhiro Tsuboi ◽  
...  

2021 ◽  
Author(s):  
Xue He ◽  
Weilong Zhang ◽  
Wei Fu ◽  
Xiaoni Liu ◽  
Ping Yang ◽  
...  

Abstract Background Acute myeloid leukemia (AML) is a significantly heterogeneous malignancy of the blood. Cytogenetic abnormalities are crucial for the prognosis of AML. However, since more than half of patients with AML are cytogenetically normal AML (CN-AML), new markers are badly required for predicting prognosis. In recent years, gene abnormalities are considered to be strong prognostic factors of CN-AML, already having clinical significance for treatment. In addition, the relationship of methylation in some genes and AML prognosis predicting has been discovered. RASGEF1A is a guanine nucleotide exchange factors of Ras, and has been reported to relate to malignancy. However, there is no research about the relationship of RASGEF1A gene and CN-AML. Methods By integrating the Cancer Genome Atlas (TCGA) database 75 patients with CN-AML and 240 Gene Expression Omnibus (GEO) database CN-AML samples, we examined the association between RASGEF1A ’s RNA expression level and DNA methylation of and AML patients’ prognosis. Then, we investigated the RASGEF1A RNA expression and DNA methylation’s prognostic value in 77 patients with AML after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) as well as 101 AML patients after chemotherapy respectively. We investigated the association between sensitivity to Crenolanib and expression level of RASGED1A in patients by integrating 191 CN-AML patients from BeatAML dadataset. Finally, we integrated the expression and methylation of RASGEF1A to predict the CN-AML patients’ prognosis. Results We found that RASGEF1A gene high expression group predicted poorer event-free survival (EFS) (P < 0.0001) as well as overall survival (OS) (P < 0.0001) in CN-AML samples, and the identical results were found in AML patients receiving chemotherapy (P < 0.0001) and Allo-HSCT (P < 0.0001). RASGEF1A RNA expression level is an CN-AML patients’ independent prognostic factor (EFS: HR = 5.5534, 95% CI: 1.2982–23.756, P = 0.0208; OS: HR = 5.3615, 95% CI: 1.1014–26.099, P = 0.0376). The IC50 (half maximal inhibitory concentration) of Crenolanib of CN-AML samples with RASGEF1A high expression level is lower. In addition, patients with high RASGEF1A methylation level had significant favorable prognosis (EPS: P < 0.0001, OS: P < 0.0001). Furthermore, the integrative analysis of expression and methylation of RASGEF1A could classify CN-AML patients into subgroups with different prognosis (EFS: P < 0.0001, OS: P < 0.0001). Conclusion Higher RASGEF1A RNA expression and lower DNA methylation predicts CN-AML patients’ poorer prognosis. The RASGEF1A high expression level from patients with CN-AML have better sensitivity to Crenolanib. The integrative analysis of RASGEF1A RNA expression and DNA methylation can provide a more accurate classification for prognosis. Lower RASGEF1A expression is a favorable prognostic factor for AML patients receiving chemotherapy or Allo-HSCT.


Author(s):  
Heather Isabella Sullivan

Ecocriticism emphasizes how our bodily and ecological boundaries are just as porous, inter-penetrable, and open as are our cultural and linguistic realms. As individual bodies and communities, we are fully immersed in our material environment and participating in constant exchanges of matter and energy. In this essay, I nevertheless advocate for a cautious approach to the ecocritical question of contested boundaries. After all, some boundaries and membranes are necessary to maintain living organisms. Regarding Timothy Morton’s assertion that we are “radically open,” I note the need for stable and healthy membranes to sustain life, such as our porous yet enclosed intestines. I propose a multi-pronged perspective using the literary model of Goethe’s famously sentimental Werther, who longs to merge with nature and become an insect, in juxtaposition with his deeply ironic Triumph of Sentimentality, which satirizes the Werther-like figure, Prince Oronaro, who wants to keep nature safely in a box. From the relationship of these two texts emerges an “ironic Werther,” a model for ecocriticism. Werther’s and Morton’s “openness” are juxtaposed with Oronaro’s boxes, allowing for an open/closed perspective that resonates with “unbalanced nature” more broadly. Ecologically speaking, all boundaries fade in the long-term, cosmic view; yet short-term boundaries allow a steady-state existence far from equilibrium, that is, they allow life to exist. Nature’s long term unbalance brings change and evolution, even as short-term bodies live, reproduce, die, and continue the process. This essay rejects the notion of harmonious nature and proposes instead a dynamic, multi-pronged view both ironic and serious, both literary and scientific, both open and closed; above all, it suggests that thinking “nature in a box” might remind us that we, too, are nature and need some limits as we hubristically alter our world.       La ecocrítica hace énfasis  en cómo nuestros límites corporales y ecológicos son tan porosos, inter-penetrables y abiertos como lo son nuestras esferas culturales y lingüísticas. Como cuerpos individuales y comunidades, estamos plenamente inmersos en nuestro medio ambiente material participando en constantes  intercambios de materia y energía. Sin embargo, este ensayo tiene como objetivo proponer  un enfoque mas cauteloso a la cuestión ecocrítica de los límites en disputa. Porque después de todo, algunos límites y membranas son necesarios para mantener a los organismos vivos. 
Con respecto a la afirmación de Timothy Morton de que estamos "radicalmente abiertos", señalo la necesidad que hay de membranas estables y saludables para mantener la vida, tal como es el caso de nuestros propios intestinos que son a la vez porosos y cerrados. Yo propongo una perspectiva con múltiples facetas, usando el modelo literario de Werther, el famoso sentimental de Goethe, quien anhela fusionarse con la naturaleza y convertirse en un insecto, en yuxtaposición con su profundamente irónico Triunfo del Sentimentalismo, que hace una sátira de la figura del Príncipe Oronaro, (personaje con características similares a las de Werther) quien quiere mantener a la naturaleza asegurada dentro de una caja.  De la relación de estos dos textos surge un "Werther irónico", que sirve de modelo para la ecocrítica. La apertura de Werther y de Morton se encuentra  yuxtapuesta con las cajas de Oronaro,  permitiendo una perspectiva abierta/cerrada que resuena mas ampliamente con la "naturaleza desequilibrada."
En términos ecológicos, todos los límites se desvanecen a largo plazo, en el panorama cósmico; sin embargo, los límites a corto plazo permiten una existencia estable lejos del equilibrio, eso quiere decir que estos límites permiten la existencia de la vida. El desequilibro a largo plazo de la naturaleza permite el cambio y la evolución, incluso mientras los cuerpos de corto plazo viven, se reproducen, mueren y continúan el proceso. Este ensayo rechaza la noción de una naturaleza armónica y propone en cambio, una perspectiva dinámica, multifacética,  que es a la vez irónica y seria; literaria y científica; abierta y cerrada. Pero sobre todo, sugiere la noción de que la "naturaleza en una caja" debería recordarnos que nosotros también somos naturaleza y necesitamos algunos límites mientras arrogantemente alteramos nuestro mundo.  


Epigenomics ◽  
2021 ◽  
Author(s):  
Camila M Loureiro ◽  
Helene A Fachim ◽  
Fabiana Corsi-Zuelli ◽  
Rosana Shuhama ◽  
Paulo R Menezes ◽  
...  

Aim: We investigated GRIN1, GRIN2A, GRIN2B and LINE-1 DNA methylation in first-episode schizophrenia patients, their nonaffected siblings and age- and sex-matched controls testing for associations between DNA methylation and exposition to childhood trauma. Materials & methods: The Childhood Trauma Questionnaire evaluated the history of childhood trauma. Genomic DNA was bisulfite converted and pyrosequencing was employed to quantify DNA methylation. Results: GRIN2A, GRIN2B and LINE-1 DNA methylation was not associated with childhood trauma in patients, siblings and controls. Siblings with childhood trauma had hypermethylation at CpG1 of GRIN1 compared with siblings without trauma. Conclusion: Childhood trauma may influence GRIN1 methylation in subjects with liability to psychosis, but not in frank schizophrenia or controls.


2017 ◽  
Vol 51 (14) ◽  
pp. 8185-8195 ◽  
Author(s):  
Jamaji C. Nwanaji-Enwerem ◽  
Elena Colicino ◽  
Lingzhen Dai ◽  
Akin Cayir ◽  
Marco Sanchez-Guerra ◽  
...  

1978 ◽  
Vol 4 (3) ◽  
pp. 5-8
Author(s):  
Ysaye Barnwell ◽  
◽  
Kathleen Klueber ◽  
H Langdon ◽  
◽  
...  

M. longitudinalis superior of the tongue was examined histologically in early (15-week) fetal specimens (N = 28). Its points of attachment and relationships are described and compared with corresponding features in the adult. This study, in particular, clarifies the relationship of the two longitudinal muscles (superior and inferior) in the tip of the tongue as well as the demarcation between the superior longitudinal and hypglossal muscles in the root of the tongue.


PLoS ONE ◽  
2009 ◽  
Vol 4 (8) ◽  
pp. e6767 ◽  
Author(s):  
Marco P. Boks ◽  
Eske M. Derks ◽  
Daniel J. Weisenberger ◽  
Erik Strengman ◽  
Esther Janson ◽  
...  

2020 ◽  
Vol 21 (3) ◽  
pp. 826 ◽  
Author(s):  
Lauren M. Webb ◽  
Kathryn E. Phillips ◽  
Man Choi Ho ◽  
Marin Veldic ◽  
Caren J. Blacker

Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD’s etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals’ unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.


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